Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)
| Group | Value (mg/m^2) |
|---|---|
| All Participants | 60 |
Trial · Interventional
TerminatedPhase 1/2Results postedRegistry dataThis trial was stopped early.
Reason given at the registry: The pharmaceutical company discontinued availability of the drug and we were forced to close the study before phase II was completed. Only one participant was enrolled on phase II.
Results were posted for this trial.
United States
1 trial · 1 stopped early · 1 with posted results
Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in People With Embryonal and Alveolar Rhabdomyosarcoma
NCT030417017 Jul 2017 to 16 Oct 2021
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Two types are embryonal RMS (ERMS) and alveolar RMS (ARMS). Dasatinib may block over-expression of a certain enzyme. Ganitumab may block a certain growth factor, which might suppress tumor growth. This drug combination may help slow tumor growth in people with ERMS and ARMS. Objective: To see if dasatinib combined with ganitumab is safe and shrinks or slows the growth of tumors in people with ERMS and ARMS. Eligibility: People any age who have ERMS or ARMS that did not respond to previous treatment and who can swallow tablets Design: Participants will be screened with: * Medical history * Physical exam * Blood, urine, and heart tests * Scans/x-rays * Tissue sample: This can be from previous surgery or biopsy. * Optional biopsy: A small piece of the tumor is removed with a needle. Participants will be asked to co-enroll in another protocol. Participants will get a drug interaction handout and wallet card that show what foods and medications to avoid. Participants will be treated in cycles. The first cycle is 35 days, and the rest are 28 days. Participants will take dasatinib by mouth daily. They will get ganitumab through an intravenous (IV) every 2 weeks. They will have a physical exam every 1-2 weeks, and urine and heart tests before most cycles. Participants will continue treatment as long as they do not have severe side effects, or their tumors do not get worse. After ending treatment, participants will have a visit. This includes repeats of the screening tests.
Experimental
Phase 1 Dose Level 1: Ganitumab and Dasatinib
Phase I Dose Level 1: Combination of ganitumab and dasatinib with limited dose escalation of dasatinib
Experimental
Phase 1 Dose Level 2: Ganitumab and Dasatinib
Phase I Dose Level 2: Combination of ganitumab and dasatinib with limited dose escalation of dasatinib
Experimental
Phase 2 Dose Level 1: Ganitumab and Dasatinib
Phase 2 Dose Level 1: Combination of ganitumab and dasatinib at the maximum tolerated dose (MTD) (or highest safe dose)
Outcomes the sponsor listed as primary.
Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)
Time frame · First 35 days of treatment
The safe dose or maximum tolerated dose (MTD) is defined as the dose level at which no more than 1 of up to 3-6 participants experience a dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of \< 5 days duration, grade 3 fever or infection \< 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.
Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib
Time frame · Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Phase II: Number of Participants That is Without Progression at 4 Months
Time frame · At 4 months
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.
Phase II: Progression Free Survival (PFS) in Participants Receiving Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib
Time frame · Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.
Phase II: Number of Participants With Stable Disease >= 6 Months as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in Participants Receiving Ganitumab With Dasatinib
Time frame · 6 months
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (i.e., at least a 30% decrease in the sum of the diameters of target lesions) nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.
Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib
Time frame · Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib
Time frame · Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
| Group | Value (mg/m^2) |
|---|---|
| All Participants | 60 |
| Group | Value (Participants) |
|---|---|
| Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg | 0 |
| Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg | 0 |
| Group | Value (Participants) |
|---|---|
| Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg | 1 |
| Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg | 0 |
| Group | Value (Months) |
|---|---|
| Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg | 1.93 |
| Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg | 0.88 |
| Group | Value (Participants) |
|---|---|
| Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg | 1 |
| Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg | 0 |
| Group | Value (Participants) |
|---|---|
| Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg | 1 |
| Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg | 3 |
| Group | Value (Participants) |
|---|---|
| Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg | 0 |
| Group | Value (Participants) |
|---|---|
| Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg | 1 |
| Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg | 2 |
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kgPhase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27 | 2 / 7 | 4 / 7 | 7 / 7 |
| Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kgPhase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27 | 1 / 6 | 5 / 6 | 6 / 6 |
| Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kgPhase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27 | 0 / 1 | 1 / 1 | 1 / 1 |
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