Skip to content

Trial · Interventional

TerminatedPhase 1/2Results postedRegistry data

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

NCTNCT03041701 (opens ClinicalTrials.gov in a new tab)Other id170049Other id17-C-0049

Overview

Status
Terminated
Phase
Phase 1/2
Enrollment
14 participants (actual)
Sponsor
National Cancer Institute (NCI) · Nih
Design
Not randomized · Open label (no masking)
Countries
1 country

United States

Start
7 Jul 2017
Primary completion
15 Sept 2021
Completion
16 Oct 2021
First posted
3 Feb 2017 (estimated)
Last update posted
14 Apr 2022
Conditions
Rhabdomyosarcoma · Rhabdomyosarcoma, Alveolar · Rhabdomyosarcoma, Embryonal

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201720182019202020212022
  1. Ph 1/2

    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

    NCT03041701

    7 Jul 2017 to 16 Oct 2021

    Terminated

Registry summary

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.

Interventions

  • DasatinibDrug
  • DasatinibDrug
  • GanitumabDrug

Arms3

  • 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)

Primary outcomes3

Outcomes the sponsor listed as primary.

  1. 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

    Registry description

    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.

  2. 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.

    Registry description

    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.

  3. Phase II: Number of Participants That is Without Progression at 4 Months

    Time frame · At 4 months

    Registry description

    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.

Secondary outcomes(4)
  1. 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.

    Registry description

    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.

  2. 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

    Registry description

    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.

  3. 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.

    Registry description

    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.

  4. 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.

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· First 35 days of treatment

Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)

GroupValue (mg/m^2)
All Participants60
Primary outcomeCount of participants· 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.

Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib

GroupValue (Participants)
Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg0
Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg0
Primary outcomeCount of participants· At 4 months

Phase II: Number of Participants That is Without Progression at 4 Months

GroupValue (Participants)
Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg1
Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg0
Secondary and other outcome results(5)
Secondary outcomeMedian· 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.

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

GroupValue (Months)
Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg1.93
Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg0.88
Secondary outcomeCount of participants· 6 months

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

GroupValue (Participants)
Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg1
Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg0
Secondary outcomeCount of participants· 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.

Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib

GroupValue (Participants)
Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg1
Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg3
Secondary outcomeCount of participants· 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.

Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib

GroupValue (Participants)
Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg0
Other pre specified outcomeCount of participants· First 35 days of treatment

Phase I: Number of Participants With a Dose-Limiting Toxicity (DLT)

GroupValue (Participants)
Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg1
Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg2

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther 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 272 / 74 / 77 / 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 271 / 65 / 66 / 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 270 / 11 / 11 / 1

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedAkshintala S, Sundby RT, Bernstein D, Glod JW, Kaplan RN, Yohe ME, Gross AM, Derdak J, Lei H, Pan A, Dombi E, Palacio-Yance I, Herrera KR, Miettinen MM, Chen HX, Steinberg SM, Helman LJ, Mascarenhas L, Widemann BC, Navid F, Shern JF, Heske CM. Phase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma. Clin Cancer Res. 2023 Sep 1;29(17):3329-3339. doi: 10.1158/1078-0432.CCR-23-0709. PMID 37398992

Eligibility

Who could join, as posted.

Sex
All
Age
from 2 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
* INCLUSION CRITERIA: * Patients of any age must have histologically or cytologically confirmed embryonal or alveolar rhabdomyosarcoma (RMS) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI) or by the Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles (CHLA). * Patients must have measurable disease. * Patients must be able to undergo appropriate imaging studies to monitor tumor response. * Archival tissue of tumors (slides or blocks (blocks preferred)) must be available for analysis. If tissue is not available, patients willing to undergo a pre-treatment biopsy may enroll. * Prior Therapies: * There is no maximum number of prior medical therapies. * There must be no curative or life prolonging treatments available. * Patients who have received other insulin-like growth factor 1 receptor (IGF-1R) antibodies or inhibitors are eligible, as long as an appropriate washout period has elapsed (see below). * Participants must have had their last fraction of external beam radiation therapy that is local and palliative at least 2 weeks prior to enrollment (except for radiation therapy to the lungs as noted below) and had their last substantial bone marrow radiation at least 6 weeks prior to enrollment. * Participants must have had their last radiation therapy of the lungs at least 8 weeks prior to enrollment. * Participants must have had their last dose of temozolomide at least 4 weeks prior to enrollment; their last dose of other cytotoxic chemotherapy at least 3 weeks prior to enrollment; their last dose of biological therapy, such as biological response modifiers (e.g., cytokines), immunomodulatory agents, vaccines, differentiating agents, used to treat their cancer at least 7 days prior to enrollment, their last dose of a monoclonal antibody the shorter of 3 half- lives or 28 days prior to enrollment, and their last dose of any investigational agent at least 4 weeks prior to enrollment. * Participants must have recovered from the acute toxic effects of prior therapy to a grade 1 (Common Terminology Criteria for Adverse Events (CTCAE) v.5.0) level prior to enrollment (does not apply to alopecia). * Age. There are no age limits for this study, but patients must have the ability to swallow tablets. * Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 or Karnofsky \>50% (if greater than or equal to 16 years of age); or children \< 16 years old must have a Lansky performance of greater than or equal to 50%. * Patients must have normal organ and marrow function as defined below: * absolute neutrophil count greater than or equal to 1,000/mcL * platelets greater than or equal to 75,000/mcL * total bilirubin less than or equal to 1.5X upper limit of normal (ULN), with exception of patients with Gilbert syndrome * Alanine aminotransferase (ALT) less than or equal to 3.0X upper limit of normal (ULN) * creatinine within normal institutional limits OR creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal. * Normal blood glucose for age * Hematologic parameters for patients undergoing biopsy only: Patients should have INR less than or equal to 1.4 and prothrombin time (PT) less than or equal to 40 seconds (unless due to lupus anticoagulant). In patients not meeting these parameters, clearance by hematology will be required prior to undergoing a biopsy. * Cardiac Function: corrected Q-T interval (QTc) \< 480 msec, and ejection fraction greater than or equal to 50% * Contraception. The effects of these agents on the developing human fetus are unknown. For this reason, men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of administration of either agent. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Negative pregnancy test is required for women of childbearing potential. * Ability of subject or Legally Authorized Representative (LAR)) to understand and the willingness to sign a written informed consent document. * Patients will be strongly encouraged to participate in 10-C-0086. If a patient does not agree to enroll on 10-C-0086, germline genetic analysis will not be performed. EXCLUSION CRITERIA: * Patients who are receiving any other investigational agents. * Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib or ganitumab or other agents used in study. * Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated list, or medical reference text such as the Physician's Desk Reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. * Patients who require concurrent treatment with antithrombotic and/or anti-platelet agents (e.g., warfarin, heparin, low molecular weight heparin, aspirin, and/or ibuprofen). * Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation r surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded. * Patients with a history of radiation pneumonitis. * Patients may not have any clinically significant cardiovascular disease including the following: * myocardial infarction or ventricular tachyarrhythmia within 6 months * major conduction abnormality (unless a cardiac pacemaker is present). Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation. The patient may be referred to a cardiologist at the discretion of the principal investigator. Patients with underlying cardiopulmonary dysfunction should be excluded from the study. * Uncontrolled intercurrent illness including, but not limited to, the following: ongoing or active infection; history of significant bleeding disorder, including congenital (von Willebrands disease) or acquired (anti-factor VIII antibodies) disorders; large pleural effusions; or psychiatric illness/social situations that would limit compliance with study requirements. * Patients with known pre-existing diabetes mellitus will be excluded because of the risk of hyperglycemia with ganitumab. * Pregnant women are excluded from this study because animal studies with dasatinib have shown embryolethality and fetal skeletal alterations at non-toxic maternal doses. Because there is an unknown but potential risk for adverse events in nursing human infants secondary to treatment of the mother with dasatinib, breastfeeding should be discontinued if the mother is treated with dasatinib.

PepBank is a research reference. Talk to a doctor before you use any peptide.