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3 Study Matches
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
12 Years and over
Phase 1/Phase 2
NCT03157128
STU 082018-008
Key
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Inclusion Criteria:
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
UT Southwestern
A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
All
12 Years and over
Phase 1/Phase 2
NCT03093116
STU-2019-1323
PHASE 1
Key
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility.
• Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• Any of the following cardiac criteria: Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
Inclusion Criteria:
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
• ECOG PS 0-1.
• Age ≥18 (or age ≥ 20 of age as required by local regulation).
• Capability to swallow capsules intact (without chewing, crushing, or opening).
• At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. PHASE 2 Key Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
• Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
• a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility. • Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor. OR
• a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility.
• Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Age ≥12 (or age ≥ 20 as required by local regulation).
• Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
• At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
• Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met. i. EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors
• Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
• Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
• Life expectancy ≥ 3 months. Key Exclusion Criteria PHASE 1 and PHASE 2
• Concurrent participation in another therapeutic clinical trial.
• Symptomatic brain metastases or leptomeningeal involvement.
• History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
• Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
• Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
• Any of the following cardiac criteria: Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.
• Known active infections (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Peripheral neuropathy of CTCAE ≥grade 2.
• History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.
Drug: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Colon, Liver, Lung/Thoracic, Pancreas, Rectum, Stomach
ALK, ROS1, NTRK, Sarcoma, Lung Neoplasms, Carcinoma, NSCL, NSCLC, Non Small Cell Lung, Thyroid Disease, Colonic Neoplasms, Thyroid Neoplasms, Carcinoma, Neuroendocrine, Respiratory Tract Neoplasms, Thoracic Neoplasms, Neoplasms by Site, Neoplasms, Lung Disease, Respiratory Tract Disease, Carcinoma, Bronchogenic, Bronchial Neoplasms, Endocrine System Disease, Colorectol Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Gastrointestinal Disease, Colonic Disease, Intestinal Disease, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Adenocarcinoma, Non Small Cell Lung Cancer, Solid Tumors, Rearrangements, TRIDENT-1, TKI, TKI naive, TKI pretreated, Anti-tumor activity, Repotrectinib, Advanced Solid Malignancies
UT Southwestern; Parkland Health & Hospital System
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.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patrick Leavey
35610
All
12 Months to 20 Years old
Phase 1
NCT02013336
STU 092013-007
Inclusion Criteria:
• 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
pediatric, MM-398, cyclophosphamide, irinotecan
Children’s Health