Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The
goal is to find the highest dose of MM-398 that can be given safely when it is used together
with the chemotherapy drug Cyclophosphamide.
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma,
neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid
Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of
a patient <18 years of age will provide informed consent and patients 11 to 18 years
of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled
blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for
pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Neuroblastoma, Sarcoma, Ewing Sarcoma, Mycosis Fungoides, Rhabdomyosarcoma, Osteosarcoma, Recurrent or Refractory Solid Tumors, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Kaposis sarcoma, Other Hematopoietic, Small Intestine, Soft Tissue
This is a multi-center, randomized, double-masked, placebo-controlled clinical trial of
suppressive valacyclovir for one year in immunocompetent study participants with an episode
of dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, and/or iritis
due to Herpes Zoster Ophthalmicus (HZO) in the year prior to enrollment.
PARTICIPANT INCLUSION CRITERIA
To be eligible for study participation, an individual must meet all of the following
criteria:
1. Ability to understand, and willingness and ability to read and sign, the informed
consent form.
2. Ability to understand and follow instructions and study procedures.
3. Willingness to comply with all study procedures and be available for the duration of
the study.
4. Ability to take oral medication, and are willing to adhere to study medication
regimen.
5. Age 18 years or older.
6. Diagnosed with HZO in one eye based on both of these criteria:
1. History of characteristic unilateral vesicular rash in the dermatomal
distribution of cranial nerve V1.
2. Medical record documentation of an episode of active dendriform epithelial
keratitis, stromal keratitis, endothelial keratitis, and/or iritis due to HZO
within the preceding year. This episode of active anterior segment ocular disease
may be due to HZO of recent onset (within the preceding 6 months); or chronic HZO
(with onset six or more months ago); may be new, worsening, or recurrent disease
after a period of inactivity; and may occur after medication was reduced.
i. Study participants with chronic HZO must be on a stable treatment regimen and off
antivirals for at least 30 days before enrollment. Study participants with chronic HZO
who do not meet this criterion may be rescreened, if they are able to meet this
criterion within 3 months after the study visit. (This is not a requirement for study
participants with recent onset HZO, who may be enrolled at any time, preferably after
completing recommended acute antiviral treatment, if prescribed, is completed).
7. For females with reproductive potential, willingness to use highly effective
contraception (e.g., hormonal contraception, barrier contraception, intrauterine
device, or abstinence).
PARTICIPANT EXCLUSION CRITERIA
An individual who meets any of the following criteria will be excluded from participation
in this study:
1. History of immunocompromised status as defined by current CDC contraindications for
the vaccine against zoster (44).
1. Study participants who are diagnosed with leukemia, lymphomas or other malignant
neoplasms affecting bone marrow or lymphatic system, unless leukemia in remission
and off chemotherapy for at least 3 months.
2. Study participants who are diagnosed with Acquired Immune Deficiency Syndrome
(AIDS) or presents with other clinical manifestations of Human Immunodeficiency
virus (HIV) including CD4 count of ≤ 200 cells/ml.
3. Study participants on immunosuppressive therapy including:
i. High-dose corticosteroids (greater than equivalent of prednisone 20 mg/day within 1
month) ii. Chemotherapy, other than low dose used for treatment of immune-mediated
diseases within 3 months iii. Study participants receiving recombinant human immune
mediators and immune modulators, especially antitumor necrosis agents, within 1 month
prior to enrollment d. Study participants with unspecified cellular immunodeficiency.
e. Study participants with history of hematopoietic stem cell transplantation.
2. Medical history of a systemic disease and thought likely to meet one of the exclusion
criteria listed in exclusion criterion #1 during the 18-month study period.
3. Renal insufficiency:
1. Requires dialysis or has history of renal transplant or
2. eGFR less than 45, determined within 30 days preceding enrollment.
4. Allergy or adverse reaction to valacyclovir or acyclovir.
5. History of vaccination against zoster within one month prior to enrollment. Study
participants who meet this exclusion criterion may be rescreened.
6. Keratoplasty or keratorefractive surgery of the involved eye with zoster.
7. On systemic antivirals with activity against herpes within the past 30 days, including
acyclovir, valacyclovir, or famciclovir, for any reason except for treatment of acute
HZO, including investigational drug trial.
8. History of another condition that may require treatment with one of these three
antivirals listed above in exclusion criterion #7, during the course of the study;
study participants who require chronic suppressive antiviral treatment with these
medications will be excluded.
9. Sexually active women who are pregnant, nursing, or in their reproductive years who do
not agree to use contraception during the 1-year treatment period.
10. Incarceration
11. Any condition or circumstance that in the opinion of the study investigator, would
place the study participant in increased risk or affect his/her full compliance or
completion of the study.
12. Participation in a clinical study testing a drug, biologic, device or other
intervention within the last 30 days from enrollment visit. Study participants who
meet this criterion may be rescreened.
The iCat2, GAIN (Genomic Assessment Informs Novel Therapy) Consortium Study
This research study is evaluating the use of specialized testing of solid tumors including
sequencing. The process of performing these specialized tests is called tumor profiling. The
tumor profiling may result in identifying changes in genes of the tumor that indicate that a
particular therapy may have activity. This is called an individualized cancer therapy (iCat)
recommendation. The results of the tumor profiling and, if applicable, the iCat
recommendation will be returned.
• Age -- Age ≤ 30 years at time of initial qualifying solid tumor diagnosis
• Diagnosis -- Histologic diagnosis of solid malignancy (excluding brain tumors and
lymphoma) that meets at least one of the following criteria:
• Refractory, defined as tumor progression after initiation of standard first line
therapy without having achieved a prior partial or complete remission OR Biopsy
proven residual disease at the completion of planned standard initial front-line
therapy.
• Recurrent, defined as tumor progression after achieving a prior partial or
complete remission
• Newly diagnosed high risk disease, defined as having an expected event free
survival of < 50% at 2 years.
• Lacks definitive diagnosis or classical genomic findings after histologic review
and standard molecular testing (rare tumor group).
• Examples include (eligibility not limited to these examples):
• Histology typically associated with a fusion in which fusion is not detected.
• Ewing-like sarcoma
• Undifferentiated sarcoma
• Inflammatory myofibroblastic tumor without ALK fusion
• Infantile fibrosarcoma without NTRK fusion
• Specimen Samples
• Sufficient tumor specimen available to meet the minimum requirements for
profiling from diagnosis or progression / recurrence
--- OR
• Surgery / biopsy planned as part of clinical care that is anticipated to yield
sufficient material to meet the minimum requirements for profiling; OR
• Patient has already had molecular profiling and patient has not yet started
matched targeted therapy based on the report .
Exclusion Criteria:
• No Therapy Planned
-- Patients who have declined further anticancer therapy will be excluded.
• Performance Status
-- Patients with Lansky (age < 16 years) or Karnofsky (age ≥16 years) score < 50 will
be excluded.
• Life Expectancy -- Patients with anticipated life expectancy < 3 months will be
excluded.
Genetic: Genetic testing and GAIN report
Sarcoma, Pediatric Solid Tumor, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Heart, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
The US food and Drug Administration (FDA) originally approved INTACS prescription inserts in
April 1999 for the correction of low levels of nearsightedness (-1.00 to -3.00 diopters).
Additional clinical data have shown that INTACS are safe for the treatment of keratoconus,
in July 2004, FDA approved INTACS inserts for the treatment of keratoconus as a Humanitarian
Use Device (FDA approval letter attached). The statute and the implementing regulation of
FDA (21 CFR 814.124 (aj) require IRB review and approval before a HUD is used.INTACS
prescription inserts are composed of two clear segments, each having an arc length of 150°,
they are manufactured form a biomedical material called polymethylmethacrylate (PMMA) and
are available in three thicknesses. Two INTACS inserts ranging from 0.250mm to 0.350mm may
be implanted depending on the orientation of the cone and the amount of myopia and
astigmatism to be reduced.
Who have experienced a progressive deterioration in their vision, such thot they can no
longer achieve adequate functional vision on a daily basis with their contact lenses or
spectacles; Who are 21 years of age or older; Who have clear central corneas; Who have a
corneal thickness of 450 microns or greater at the proposed incision site; Who have
corneal transplantation as the only remaining option to improve their functional vision.
Exclusion Criteria:
Who have abnormally thin corneas or who have a corneal thickness of 449 microns or less at
the proposed incision site;
Patients with collagen vascular, autoimmune or immunodeficiency disease;
Pregnant or nursing patients;
Presence of ocular conditions, such as recurrent corneal erosion syndrome or corneal
dystrophy, that my predispose the patient to future complications;
Patients who are taking on or more of following medications: isotretinoin (Accutane);
amiodarone HCL (Cordarone).
Effects of Hypoglossal Nerve Stimulation on Cognition and Language in Down Syndrome and Obstructive Sleep Apnea
This study is a prospective, single-arm study conducted under a common implant and follow-up
protocol. The objective will be to follow fifty-seven (57) adolescents and young adults
(10-21 years of age), with Down syndrome, moderate to severe sleep apnea, and
post-adenotonsillectomy, for 12 months after undergoing implant of the Inspire Upper Airway
Stimulation (UAS) System. The study is being conducted in order to evaluate objective change
in cognition and expressive language after implant and therapy with the Inspire UAS System.
• Diagnosis of Down syndrome
• Age 10-21 years
• Prior adenotonsillectomy
• Severe OSA (AHI > 10, AHI < 50, no more than 25% AHI attributable to central events)
based on prior in-lab PSG performed after adenotonsillectomy and within 18 months of
enrollment
• Approval from at least two of the three physician reviewers based upon the results of
a routine drug-induced sleep endoscopy (DISE) having occurred within 12 months of
enrollment
• Subjects must have either tracheotomy or be ineffectively treated with CPAP due to
non-compliance, discomfort, un-desirable side effects, persistent symptoms despite
compliance use, or refusal to use the device
• Children and their parents/guardians must be willing to have stimulation hardware
permanently implanted, and be willing to participate in follow-up visits,
postoperative PSG, and questionnaire completion
• Children's parents/guardians must complete a questionnaire confirming that their child
is capable of communicating feelings of pain or discomfort. They must also confirm
they are able to assess their child for adverse effects related to device implantation
• Children and their parents/guardians must be proficient in English
Exclusion Criteria:
• Body mass index (BMI) above the 95th percentile for subject's age
• Circumferential airway collapse at the level of the velopharynx observed during DISE
• Other medical conditions resulting in medical instability (eg. congestive heart
failure, recent open heart surgery, immunosuppression, or chronic lung disease or
aspiration)
• Presence of another medical condition requiring future magnetic resonance imaging
(MRI) of the chest
• Patients with another implantable device which could interact unintentionally with the
Inspire system
• Any contraindication for general anesthesia
• History of bleeding or clotting disorders and those on blood thinning or NSAID
medications for the week prior to implantation surgery. Subjects will be asked to
refrain from the use of NSAIDS for two weeks after implantation or any revision
surgeries
• Subject is currently taking muscle relaxant medication
• Life expectancy less than 12 months
• Subject's inability to communicate pain or discomfort to their caretaker/parent, based
on parental or investigator assessment
• Nonverbal candidates will be excluded due to an inability to complete testing
procedures including expressive language sampling
• Subjects with a co-occurring diagnosis of autism spectrum disorder
• Subjects that have a positive β-HCG
• Subjects deemed unfit for participation by the investigator for any other reason
Device: Inspire Upper Airway Stimulation (UAS) System
Obstructive Sleep Apnea, Down Syndrome, Ear, Nose, Throat
Stereotactic Radiosurgery (SRS) for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true
tolerable doses, which may exceed the current standard doses. This may lead to an improvement
in local control, patient survival, and/or quality-of life.
Inclusion Criteria
1. Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ
cell cancer, or unknown primary tumor.
2. Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or
intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI
contrast, an MRI without contrast is acceptable if lesions are visible)
3. All brain metastases must be outside the brain stem (midbrain, pons and medulla).
4. Patient must have 10 or less brain metastases.
5. The maximum diameter of any lesion must be less than or equal to 3.0 cm.
6. Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any
targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one
additional brain metastasis that can be targeted with SRS
7. Age ≥ 18 years.
8. ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or
better.
9. All men, as well as women of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
marital status, having undergone a tubal ligation, or remaining celibate by choice)
who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
Medically acceptable birth control (contraceptives) includes:
• Approved hormonal contraceptives (such as birth control pills, patch, or ring:
Depo-Provera, Implanon), or
• Barrier methods (such as a condom or diaphragm) used with a spermicide (a
substance that kills sperm)
10. Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria
1. Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
2. Patients with leptomeningeal metastasis.
NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive
CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal
involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal
enhancement by imaging (MRI) would be considered to have LMD even in the absence of
positive CSF cytology, unless a parenchymal lesion can adequately explain the
neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally
symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would
not be considered to have LMD. In that patient, CSF sampling is not required to
formally exclude LMD, but can be performed at the investigator's discretion based on
level of clinical suspicion.
3. Patients with a contraindication to both MRI (with or without contrast) and CT scan
(with contrast)
4. Patients with life expectancy < 3 months.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that, in the opinion of the
investigator, would limit compliance with study requirements.
6. Subjects must not be pregnant or nursing at the time of SRS treatment due to the
potential for congenital abnormalities and the potential of this regimen to harm
nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Lymphoma, Sarcoma, Multiple Myeloma, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Hodgkins Lymphoma, Lymphoid Leukemia, Small Intestine, Soft Tissue
UT Southwestern; Parkland Health & Hospital System
• 2 to 21 years of age
• Have a visually significant cataract or need IOL replacement surgery
• Compromised capsular bag prohibiting implantation of standard posterior IOL
• Subject or parent/guardian must be able to comply with visit schedule and study
requirements
• Subject's legal representative must be able to sign the Informed Consent
Exclusion Criteria:
• Under 2 years of age
• Unable to meet Postoperative evaluation requirements
• No useful vision or vision potential in fellow eye
• Mentally retarded patients
• History of corneal disease
• Abnormality of the iris or ocular structure
• ACD less than 3.2 mm
• Uncontrolled glaucoma
• IOP > 25 mmHg
• Chronic or recurrent uveitis
• Preexisting macular pathology that may complicate the ability to assess the benefit of
this lens
• Retinal detachment or family history
• Retinal disease that may limit visual potential
• Optic nerve disease that may limit visual potential
• Diabetes mellitus
• Pregnant, lactating or plan to become pregnant
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
A study to learn about safety and find out maximum tolerable dose of palbociclib given in
combination with chemotherapy (temozolomide with irinotecan or topotecan with
cyclophosphamide) in children, adolescents and young adults with recurrent or refractory
solid tumors (phase 1). Phase 2 to learn about the efficacy of palbociclib in combination
with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the
treatment of children, adolescents, and young adults with recurrent or refractory Ewing
sarcoma (EWS).
Inclusion:
1. Histologically confirmed relapsed or refractory solid tumor as follows:
• For dose escalation and dose determination parts: Histologically confirmed
relapsed or refractory solid tumor (including CNS tumors but not lymphomas).
Patients with Diffuse Intrinsic Pontine Glioma do not require histological only
radiographic confirmed relapse to enroll.
• For dose expansion and tumor specific cohorts: Histologically confirmed relapsed
or refractory solid tumor including but not limited to EWS, rhabdoid tumor,
rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse
Intrinsic Pontine Glioma do not require histological only radiographic confirmed
relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
• For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis
or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement.
Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners
is required OR availability of formalin fixed paraffin embedded (FFPE) tumor
tissue sample for central testing. Patient must have relapsed or have refractory
disease and at least evaluable disease in at least one site other than bone
marrow that can be followed by imaging.
2. Age ≥2 and <21 years at the time of study entry.
3. Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative
Oncology Group (ECOG) 0, 1 or 2 for patients >16 years of age.
4. Adequate bone marrow function.
• Absolute neutrophil count ≥1000/mm3;
• Platelet count ≥100,000/mm3 (transfusion independent, no platelet transfusion in
past 7 days prior study entry);
• Hemoglobin ≥8.5 g/dL (transfusion allowed).
5. Adequate renal function: Serum creatinine level based on age/gender must within
protocol specified limits.
6. Adequate liver function, including:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to
disease involvement of the liver;
• Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's
syndrome.
7. Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have
measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS
disease or INRC for neuroblastoma. Patients with EWS enrolled to Phase 2 portion of
the study are eligible with evaluable disease (eg, bone only disease with no soft
tissue component).
8. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute
toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy,
differentiation therapy or biologic therapy, with the exception of alopecia.
9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and
at the baseline visit.
Exclusion:
1. Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination,
prior treatment with a CDK4/6 inhibitor or progression while on treatment with an
IRN-containing regimen that includes TMZ. Patients who have received the combination
of IRN and TMZ and did not progress while on these medications are eligible. For
patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment
with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing
regimen that includes CTX. Patients who have received the combination of TOPO and CTX
and did not progress while on these medications are eligible. Phase 2 portion: prior
treatment with a CDK4/6 inhibitor or progression while on treatment with an
IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ
and did not progress while on these medications are eligible.
2. Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ
combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination.
3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. Patients who are
receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors
within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN
and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12
days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See
Section 5.7.1 for list of products.)
4. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for
nitrosoureas.
5. Prior irradiation to >50% of the bone marrow (see Appendix 9).
6. Participation in other studies involving investigational drug(s) within 2 weeks or 5
half lives, whichever is longer, prior to study entry.
7. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line
placement are not considered major surgeries.
8. For IRN and TMZ with/without palbociclib combinations: known or suspected
hypersensitivity to palbociclib, IRN and/or TMZ. For combination of palbociclib with
TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
9. Patients with known symptomatic brain tumors or brain metastases and require steroids,
unless they have been on a stable or on a decreasing steroid dose for >14 days.
10. Patients with previously diagnosed brain metastases are eligible if they have
completed their prior treatment and have recovered from the acute effects of radiation
therapy or surgery prior to study entry for these metastases for at least 14 days post
radiation and 4 weeks post-surgery and are neurologically stable.
11. Hereditary bone marrow failure disorder.
12. QTc >470 msec.
13. History of clinically significant or uncontrolled cardiac disease, including:
• History of or active congestive heart failure; if patient had congestive heart
failure resolve and >1 year from resolution, patient will be considered eligible;
• Clinically significant ventricular arrhythmia (such as ventricular tachycardia,
ventricular fibrillation or Torsades de Pointes);
• Diagnosed or suspected congenital or acquired prolonged QT syndrome;
• Need for medications known to prolong the QT interval;
• Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT
interval;
• Left ventricular ejection fraction <50% or shortening fraction <28%.
14. Recent or ongoing clinically significant gastrointestinal disorder that may interfere
with absorption of orally administered drugs (eg, gastrectomy).
15. Severe acute or chronic medical or laboratory test abnormality that may increase the
risk associated with study participation or investigational product administration or
may interfere with the interpretation of study results, and in the judgment of the
Investigator, would make the patient inappropriate for entry into this study.
16. Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
patients who are Pfizer employees, including their family members, directly involved
in the conduct of the study.
Neuroblastoma, Sarcoma, Solid Tumors, Ewing Sarcoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma, Rhabdomyosarcoma, Rhabdoid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Kaposis sarcoma, Small Intestine, Soft Tissue, Ill - Defined Sites
A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
This phase III trial studies if selumetinib works just as well as the standard treatment with
carboplatin/vincristine (CV) for subjects with NF1-associated low grade glioma (LGG), and to
see if selumetinib is better than CV in improving vision in subjects with LGG of the optic
pathway (vision nerves). Selumetinib is a drug that works by blocking some enzymes that
low-grade glioma tumor cells need for their growth. This results in killing tumor cells.
Drugs used as chemotherapy, such as carboplatin and vincristine, work in different ways to
stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. It is not yet known whether selumetinib works better in
treating patients with NF1-associated low-grade glioma compared to standard therapy with
carboplatin and vincristine.
• Patients must be >= 2 years and =< 21 years at the time of enrollment
• Patients must have a body surface area (BSA) of >= 0.5 m^2 at enrollment
• Patients must have neurofibromatosis type 1 (NF1) based on clinical criteria and/or
germline genetic testing
• Patients must be newly diagnosed or have previously diagnosed NF-1 associated LGG that
has not been treated with any modality other than surgery
• For patients with optic pathway gliomas (OPGs):
• Newly-diagnosed patients with OPG are eligible if there are neurologic symptoms
(including visual dysfunction, as defined below) or other exam findings
associated with the tumor
• Previously-diagnosed patients with OPG are eligible if they have new or worsening
neurologic symptoms (including visual dysfunction, as defined below) or have
tumor growth
• For both newly-diagnosed and previously-diagnosed OPG, the patient may be
eligible, irrespective of whether there has been tumor growth or other
neurological symptoms or worsening, if they meet at least one of the following
visual criteria:
• Visual worsening, defined as worsening of visual acuity (VA) or visual
fields (VF) documented within the past year (by examination or history); OR
• Significant visual dysfunction (defined as VA worse than normal for age by
0.6 logMAR [20/80, 6/24, or 2.5/10] or more in one or both eyes)
• For patients with LGG in other locations (i.e., not OPGs):
• Newly-diagnosed patients with LGG are eligible if there are neurologic symptoms
or other exam findings associated with the tumor
• NOTE: Newly-diagnosed patients with LGG without associated neurologic
symptoms or exam findings are not eligible
• Previously-diagnosed patients with LGG are eligible if they have new or worsening
neurologic symptoms or have tumor growth
• Although not required, if a biopsy/tumor resection is performed, eligible histologies
will include all tumors considered LGG or low-grade astrocytoma (World Health
Organization [WHO] grade I and II) by 5th edition WHO classification of central
nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
• Patients must have two-dimensional measurable tumor >= 1 cm^2
• Patients with metastatic disease or multiple independent primary LGGs are allowed on
study
• Creatinine clearance or radioisotope glomerular filtration Rate (GFR) >= 70
mL/min/1.73 m^2 OR a serum creatinine based on age/gender (within 7 days prior to
enrollment) as follows:
• Age; maximum serum creatinine (mg/dL)
• 2 to < 6 years; 0.8 (male) and 0.8 (female)
• 6 to < 10 years; 1 (male) and 1 (female)
• 10 to < 13 years; 1.2 (male) and 1.2 (female)
• 13 to < 16 years; 1.5 (male) and 1.4 (female)
• >= 16 years; 1.7 (male) and 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to
enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study
regardless of their total and indirect [unconjugated] bilirubin levels as long as
their direct [conjugated] bilirubin is < 3.1 mg/dL)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x
upper limit of normal (ULN) = 135 U/L (within 7 days prior to enrollment). For the
purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL (within 7 days prior to enrollment)
• Left ventricular ejection fraction (LVEF) >= 53% (or institutional normal; if the LVEF
result is given as a range of values, then the upper value of the range will be used)
by echocardiogram (within 4 weeks prior to enrollment)
• Corrected QT (QTc) interval =< 450 msec by electrocardiography (EKG) (within 4 weeks
prior to enrollment)
• Absolute neutrophil count >= 1,000/uL (unsupported) (within 7 days prior to
enrollment)
• Platelets >= 100,000/uL (unsupported) (within 7 days prior to enrollment)
• Hemoglobin >= 8 g/dL (may be supported) (within 7 days prior to enrollment)
• Patients with a known seizure disorder should be stable and should have not
experienced a significant increase in seizure frequency within 2 weeks prior to
enrollment
• Patients 2-17 years of age must have a blood pressure that is =< 95th percentile for
age, height, and gender at the time of enrollment. Patients >= 18 years of age must
have a blood pressure =< 130/80 mmHg at the time of enrollment (with or without the
use of antihypertensive medications).
• Note: Adequate blood pressure can be achieved using medication for the treatment
of hypertension
• All patients must have ophthalmology toxicity assessments performed within 4 weeks
prior to enrollment
• For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors)
and/or spine (depending on the site(s) of primary disease) with and without contrast
must be performed within 4 weeks prior to enrollment
• For patients who undergo a surgery on the target tumor (not required), a pre- and
post-operative* MRI of the brain (with orbital cuts for optic pathway tumors) or spine
(depending on the site(s) of primary disease) with and without contrast must also be
performed within 4 weeks prior to enrollment
• The post-operative MRIs should be performed ideally within 48 hours after surgery
if possible
• Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age
• Patients must have the ability to swallow whole capsules
• Patients must have receptive and expressive language skills in English or Spanish to
complete the quality of life (QOL) and neurocognitive assessments
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
• Patients must not have received any prior tumor-directed therapy including
chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior
surgical intervention is permitted
• Patients with a concurrent malignancy or history of treatment (other than surgery) for
another tumor within the last year are ineligible
• Patients may not be receiving any other investigational agents
• Patients with any serious medical or psychiatric illness/ condition, including
substance use disorders likely in the judgement of the investigator to interfere or
limit compliance with study requirements/treatment are not eligible
• Patients who, in the opinion of the investigator, are not able to comply with the
study procedures are not eligible
• Female patients who are pregnant are not eligible since fetal toxicities and
teratogenic effects have been noted for several of the study drugs. A pregnancy test
is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants are not eligible
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
12 weeks after stopping study therapy are not eligible
• Note: Women of child-bearing potential and males with sexual partners who are
pregnant or who could become pregnant (i.e., women of child-bearing potential)
should use effective methods of contraception for the duration of the study and
for 12 weeks after stopping study therapy to avoid pregnancy and/or potential
adverse effects on the developing embryo
• Cardiac conditions:
• Known genetic disorder that increases risk for coronary artery disease. Note: The
presence of dyslipidemia in a family with a history of myocardial infarction is
not in itself an exclusion unless there is a known genetic disorder documented
• Symptomatic heart failure
• New York Heart Association (NYHA) class II-IV prior or current cardiomyopathy
• Severe valvular heart disease
• History of atrial fibrillation
• Ophthalmologic conditions:
• Current or past history of central serous retinopathy
• Current or past history of retinal vein occlusion or retinal detachment
• Patients with uncontrolled glaucoma
• If checking pressure is clinically indicated, patients with intraocular
pressure (IOP) > 22 mmHg or ULN adjusted by age are not eligible
• Ophthalmological findings secondary to long-standing optic pathway glioma (such
as visual loss, optic nerve pallor, or strabismus) or longstanding
orbito-temporal plexiform neurofibroma (PN), such as visual loss, strabismus)
will NOT be considered a significant abnormality for the purposes of the study
• Treatments and/or medications patient is receiving that would make her/him ineligible,
such as:
• Supplementation with vitamin E greater than 100% of the daily recommended dose.
Any multivitamin containing vitamin E must be stopped prior to study enrollment
even if less than 100% of the daily recommended dosing for vitamin E
• Surgery within 2 weeks prior to enrollment, with the exception of surgical
placement for vascular access or cerebrospinal fluid (CSF) diverting procedures
such as endoscopic third ventriculostomy (ETV) and ventriculo-peritoneal (VP)
shunt.
• Note: Patients must have healed from any prior surgery prior to enrollment
• Patients who have an uncontrolled infection are not eligible
FX-322 in Adults With Acquired Sensorineural Hearing Loss
This is a Phase 2, prospective, randomized, double-blind, placebo-controlled, single-dose,
multicenter study to evaluate the efficacy of FX-322, administered by intratympanic
injection, in adults with acquired sensorineural hearing loss (SNHL).
1. Subject has read and voluntarily signed the Informed Consent Form (ICF) after all
questions have been answered and prior to any study-mandated procedure.
2. Adult aged 18-65 years inclusive at Screening.
3. Documented medical history consistent with acquired, adult onset, sensorineural
hearing loss associated with noise-induced SNHL (NIHL) or idiopathic sudden SNHL
(SSNHL) (documented audiogram at least 6 months prior to screening required).
4. A pure tone average at the Screening Visit of 35-85 dB at 500Hz, 1000Hz, 2000Hz, and
4000Hz in the ear to be injected.
5. Ability to communicate well with the Investigator and is willing to comply with and
complete all the study procedures.
6. Female subjects must be of non-childbearing potential or will need to utilize two
methods of highly effective contraception during the study participation (e.g.
hormonal contraception and condom or an intrauterine device and condom) or remain
abstinent. Male subjects should use condoms with spermicide during the course of the
study or remain abstinent. Subjects should not donate sperm or ova during the study
period.
7. Have met additional masked criteria as determined by the Electronic Data Capture
system.
Exclusion Criteria:
1. Subject has previously been randomized in a FX-322 clinical trial.
2. Perforation of tympanic membrane or other tympanic membrane disorders that would
interfere with the delivery and safety assessment of an intratympanic medication or
reasonably be suspected to affect tympanic membrane healing after injection in study
ear. This includes a current tympanostomy tube.
3. Any conductive hearing loss of greater than 15 dB at a single frequency or greater
than 10dB at two or more contiguous octave frequencies in the study ear at the
Screening visit.
4. Active chronic middle ear disease or a history of major middle ear surgery, as an
adult, in the ear to be injected.
5. Subject has had an intratympanic injection in either ear within 3 months of the
screening visit.
6. Evidence of or previous diagnosis of auditory neuropathy, traumatic brain injury,
"central" hearing loss, or genetic hearing loss.
7. History of chronic, recurrent clinically significant vestibular symptoms.
8. History of bilateral sudden sensorineural hearing loss or recurrent sudden
sensorineural hearing loss.
9. History of clinically significant systemic autoimmune disease (e.g. rheumatoid
arthritis, Sjogren's syndrome, multiple sclerosis, psoriasis).
10. History of head or neck radiation, treatment, or exposure to platinum based
chemotherapy drugs or aminoglycosides.
11. Exposure to another investigational drug within 28 days prior to screening visit.
12. Evidence of any active or chronic disease or condition that could interfere with, or
for which the treatment of might interfere with, the conduct of the study, or that
would pose an unacceptable risk to the subject in the opinion of the investigator
following a detailed medical history, physical examination, and vital signs (systolic
and diastolic blood pressure, pulse rate, body temperature).
13. Positive urine pregnancy test or breast-feeding.
14. Any known factor, condition, or disease that, in the view of the Investigator, might
interfere with treatment compliance, study conduct or interpretation of the results.
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating
loss of appetite in patients with cancer that has spread to other places in the body
(advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if
olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and
preventing weight loss.
• Women and men of reproductive potential should agree to use an appropriate method of
birth control throughout their participation in this study due to the teratogenic
potential of the therapy utilized in this trial. Appropriate methods of birth control
include abstinence, oral contraceptives, implantable hormonal contraceptives or double
barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or
physician-estimated caloric intake of less than 20 calories/kilogram of body weight
per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an
appetite score of 4 or worse on the "Please rate your appetite…." question that
requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of
registration
• Not currently using systemic adrenal steroids (with the exception of short-term
dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the
past month
• Patient should not have poorly controlled hypertension or congestive heart failure at
registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or
intractable vomiting (defined as vomiting more than 3 times per day over the preceding
week)
• Not currently using olanzapine for another medical condition or had previously used
olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may
have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had
left patients with compromised taste, which has not resolved at the time of
registration
• Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown. Therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit
of normal (ULN)
• Fasting glucose > 1410 mg/dl
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine,
clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be
able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking
patients should have access to Spanish speaking staff on site or through the use of a
translation service to be able to conduct the informed consent discussion in Spanish,
and to conduct the weekly phone calls
Exclusion Criteria:
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency
virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion
of the treating physician, would make this protocol unreasonably hazardous for the
patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia
or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate
cancer (this exclusion criterion is intended to circumvent any confounding
antineoplastic effects of megestrol acetate)
Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment
that is directed by genetic testing works in pediatric patients with solid tumors,
non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one
line of standard systemic therapy and/or for which no standard treatment exists that has been
shown to prolong survival. Genetic tests look at the unique genetic material (genes) of
patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit
more from treatment which targets their tumor's particular genetic mutation, and may help
doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and
=< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or
refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g.
langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic
sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had
histologic verification of malignancy at original diagnosis or relapse except in
patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with
pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers
including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where
patient enrolls prior to histologic confirmation of recurrent disease, patient is
ineligible and should be withdrawn from study if histology fails to confirm
recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are
not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor
sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from
start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed
paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy
or surgery that was performed at any point after initial tumor recurrence/progression,
or be planned to have a procedure to obtain such a sample that is considered to be of
potential benefit by the treating clinicians; a tumor sample from a clinically
performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto
Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse
intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized
acid-based decalcification methods are not generally suitable for MATCH study
testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report
availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting
2022): In stage 2 of the study, no tumor samples will be submitted for centralized
clinical tumor profiling; instead, a tumor molecular profiling report from a College
of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments
(CLIA)-approved testing laboratory must be submitted for review by the Molecular
Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was
obtained at any point after initial tumor recurrence/progression and must be
accompanied by a pathology report for the same tumor specimen; a molecular
profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable
for enrollment onto Pediatric MATCH only for children with high-grade gliomas of
the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that
molecular profiling reports are available from multiple timepoints, the most
recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients >
16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic
deficits in patients with central nervous system (CNS) tumors must have been stable
for at least 7 days prior to study enrollment; patients who are unable to walk because
of paralysis, but who are up in a wheelchair, will be considered ambulatory for the
purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have
radiographically measurable disease; measurable disease based on imaging obtained less
than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not
have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable
disease are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance
imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all
subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but
will need to meet all criteria prior to enrollment on any assigned treatment
subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of
treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years
of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in
patients with CNS tumors must have been stable for at least 7 days prior to study
enrollment; patients who are unable to walk because of paralysis, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the performance
score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol
specified therapy, the patients must have radiographically measurable disease;
patients with neuroblastoma who do not have measurable disease but have MIBG+
evaluable are eligible; measurable disease in patients with CNS involvement is defined
as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression
post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for
RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a
subprotocol, the following general criteria for initiation of therapy will be
required:
• Patients must have fully recovered from the acute toxic effects of all prior
anticancer therapy and must meet the following minimum duration from prior
anticancer directed therapy prior to enrollment to the subprotocol; if after the
required timeframe, the numerical eligibility criteria are met, e.g. blood count
criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be
myelosuppressive: for agents not listed, the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator prior to enrollment >= 21 days after the last dose of cytotoxic
or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with
reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the
last dose of agent; for agents not listed, the duration of this interval
must be discussed with the study chair and the study-assigned research
coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of
antibody, and toxicity related to prior antibody therapy must be recovered
to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior
therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a
long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth
factor; for agents that have known adverse events occurring beyond 7 days
after administration, this period must be extended beyond the time during
which adverse events are known to occur; the duration of this interval must
be discussed with the study chair and the study-assigned research
coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth
factors): >= 21 days after the completion of interleukins, interferon or
cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any
stem cell infusion including donor lymphocyte infusion (DLI) or boost
infusion: >= 84 days after infusion and no evidence of graft versus
host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular
therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells,
etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days
after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to
>= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM)
radiation; note: radiation may not be delivered to "measurable disease"
tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42
days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without
known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow
metastatic disease will be eligible for study provided they meet the blood counts (may
receive transfusions provided they are not known to be refractory to red cell or
platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope
glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on
age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated +
unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase
(SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN
for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact
capsules/tablets, unless otherwise specified in the subprotocol to which they are
assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior
therapy will be included with specific treatment subprotocols
Exclusion Criteria:
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not
be entered on this study due to risks of fetal and teratogenic adverse events as seen
in animal/human studies, or because there is currently no available information
regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in
females who are post-menarchal; males or females of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific
subprotocols, patients receiving corticosteroids who have not been on a stable or
decreasing dose of corticosteroid for at least 7 days prior to enrollment to the
subprotocol will not be eligible; if used to modify immune adverse events related
to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time
of consent and enrollment to a subprotocol; other investigational agents may not
be administered to patients while they are receiving study drug as part of a
subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of
consent and enrollment to a subprotocol; other investigational agents may not be
administered to patients while they are receiving study drug as part of a
subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled
infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ
transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will
be included with specific treatment subprotocols
Evaluation of [18F]FLT PET/CT as an Early Predictor of Outcome in Pediatric Solid Tumors
The experimental [18F]FLT-PET/CT will be completed before initiation of chemotherapy at
either diagnosis or initiation of salvage chemotherapy at relapse and prior to the third
cycle (or month) of chemotherapy. Laboratory analysis and correlative radiology, as directed
per clinical care based on the primary diagnosis, are required within 30 days of the baseline
[18F]FLT PET/CT. Follow-up will comprise 24 months of standard practice treatment and follow
up.
• Patients with histologically confirmed solid tumor malignancies with residual tumors
present that require standard of care chemotherapy for a minimum number of cycles. All
anatomical sites and all tumor histologies are eligible including central nervous
system tumors. Both newly diagnosed and/or newly relapsed patients are eligible.
• Patients ages 8 •25 years
• In the opinion of the investigator, patients must be thought to be able to lie still
for imaging without sedation for 20 •30 minutes.
• Patients must have a performance status of > 50% (Lansky or Karnofsky).
• Patients of childbearing potential must have a negative urine or serum pregnancy test
as per institution's standard of care within 7 days prior to [18F]FLT PET/CT imaging.
• Ability to understand and the willingness to sign a written informed consent/assent.
Exclusion Criteria:
• Patients with known allergic or hypersensitivity reactions to previously administered
radiopharmaceuticals of similar chemical or biologic composition to [18F]FLT
• Newly diagnosed subjects who had prior chemotherapy or radiotherapy before enrollment
in the study. Relapsed patients are eligible prior to starting their relapsed
chemotherapy regimen if they meet the other eligibility criteria.
• Subjects for whom chemotherapy is not a standard of care primary therapy option.
• Patients who are pregnant or breast-feeding.
• Patients with no residual tumor (i.e. complete resection at diagnosis or relapse).
Drug: [18F]FLT-PET/CT
Sarcoma, Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Small Intestine, Soft Tissue
Multi-Center Study on Performance of the Ponto Implant System Using Minimally Invasive Ponto Surgery (in Adult Patients)
This prospective, multi-center study funded by Oticon Medical AB will be conducted at six
clinical sites in North America. Patients with a hearing loss and that are already planned
for treatment with a percutaneous (through the skin) bone-anchored hearing system (BAHS) will
be included in the study. The total number of participants included in the study will be 64.
The purpose of this study is to investigate the rate of successful BAHS use after
implantation of the Ponto Implant system using the surgical technique Minimally Invasive
Ponto Surgery (MIPS).
• 18 years of age or older
• Patient indicated for surgical intervention with a bone anchored hearing system
according to local clinic's standard guidelines.
• Normal bone quality and bone thickness above 3 mm, where no complications during
surgery are expected.
• Skin thickness of 12mm or less at the implant site
Exclusion Criteria:
• Patients undergoing re-implantation
• Patients who are unable or unwilling to follow investigational
procedures/requirements, e.g. to complete quality of life scales.
• Diseases or treatments known to compromise the bone quality at the implant site, e.g.
radiotherapy, osteoporosis, diabetes mellitus
• Known conditions (e.g. uncontrolled diabetes) that could jeopardize skin condition and
wound healing over time as judged by the investigator.
• Any other known condition that the investigator determines could interfere with
compliance or study assessments.
PEDIATRIC SONICS: Pediatric Study of Neuropsychology and Imaging in CNS Demyelinating Syndromes. (SONICS)
Central Nervous System (CNS) demyelinating conditions include multiple sclerosis (MS), Acute
Disseminated Encephalomyelitis (ADEM), Neuromyelitis Optica Spectrum Disorder (NMOSD) and
Transverse Myelitis (TM). The symptoms of these conditions are quite variable from patient to
patient, but can include motor, sensory, visual, gait and cognitive changes. Conventional MRI
can be used to look for new anatomic changes, but fails to measure underlying biochemical
changes in brain tissue. The purposes of this study are to identify the biologic and anatomic
correlations between cognitive profiles and disease activity using MRI imaging techniques.
1. Diagnosis of Multiple Sclerosis , ADEM, anti-MOG antibody associated CNS demyelination
2. Age 12 to 18 inclusive at time of enrollment
3. Ability of parent or legal guardian to provide informed consent if participant is
under 18.
4. Ability of patients age 12 and older to give assent
5. Completion of the signed HIPPA authorization form by a parent or legal guardian or by
participants (18 years of age).
Exclusion Criteria:
1. Known history of traumatic brain injury that required medical care
2. Non-English speaking (based on standardized neuropsychological testing and
questionnaires)
3. Claustrophobic, pregnant, the presence of metallic braces, implants or medical devices
that are unsafe at 3T or 7T and/or interfere with the MRI/MRS signals
Neuromyelitis Optica, Transverse Myelitis, Acute Disseminated Encephalomyelitis, Multiple Sclerosis, Relapsing-Remitting, Head and Neck