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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

This study is currently recruiting participants.
See Contacts and Locations
Verified February 24, 2017 by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT03041701
First received: February 2, 2017
Last updated: July 11, 2017
Last verified: February 24, 2017
  Purpose

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 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.


Condition Intervention Phase
Rhabdomyosarcoma Rhabdomyosarcoma- Alveolar Rhabdomyosarcoma-Embryonal Drug: Dasatinib Drug: Ganitumab Phase 1 Phase 2

National Cancer Institute (NCI) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of the Insulin-Like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in Patients With Embryonal and Alveolar Rhabdomyosarcoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):

Primary Outcome Measures:
  • Phase I: To determine the safe dose of dasatinib when given with ganitumab in patients with relapsed or refractory embryonal or alveolar RMS. [ Time Frame: Prior to cycle 2, 3, 5, 7 etc. ]
  • Phase II: To determine if the use of ganitumab plus dasatinib is able to be associated with a modest fraction of patients who experience an objective clinical response (CR and PR) as defined by RECIST criteria. [ Time Frame: Prior to cycle 2, 3, 5, 7 etc. ]

Secondary Outcome Measures:
  • To assess the PFS in patients receiving this combination. [ Time Frame: Prior to cycle 2,3,5,7 etc. ]
  • To determine the fraction of patients with stable disease >= 6 months as defined by RECIST criteria in patients receiving this combination. [ Time Frame: Prior to cycle 2,3,5,7 etc. ]
  • To describe the toxicity and confirm the tolerability of the combination of ganitumab and dasatinib in patients with relapsed or refractory RMS. [ Time Frame: Prior to cycle 2,3,5,7 etc. ]

Estimated Enrollment: 24
Actual Study Start Date: July 7, 2017
Estimated Study Completion Date: October 31, 2021
Estimated Primary Completion Date: January 1, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I
Dasatinib daily and ganitumab once every 2 weeks.
Drug: Dasatinib
Once daily on days -7 through day 27 during cycle 1, and then days 0-27 for subsequent cycles.
Drug: Ganitumab
Once every 2 weeks beginning on day 0.
Experimental: Phase II
Dasatinib MTD derterimed during phase I and ganitumab every 2 weeks.
Drug: Dasatinib
Once daily on days -7 through day 27 during cycle 1, and then days 0-27 for subsequent cycles.
Drug: Ganitumab
Once every 2 weeks beginning on day 0.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 99 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients of any age must have histologically or cytologically confirmed embryonal or alveolar rhabdomyosarcoma (RMS) confirmed by the Laboratory of Pathology, NCI.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.
  • 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 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, and had their last substantial bone marrow radiation at least 6 weeks prior to enrollment.
    • Participants must have had their last dose of alkylating agents at least 4 weeks prior to enrollment and at least 3 weeks from other cytotoxic chemotherapy; 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 at least 3 halflives 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 (CTCAE v.4.0) 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.
  • 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 100,000/mcL
    • total bilirubin less than or equal to 1.5X upper limit of normal (ULN), with exception of patients with Gilbert syndrome, ALT less than or equal to 3.0X 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 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: 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 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.
  • QTc prolongation (defined as a QTc interval greater than or equal to 480 msec) or other significant ECG abnormalities.
  • 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 IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain dasatinib tablets are excluded.
  • Patients may not have any clinically significant cardiovascular disease including the following:

    • myocardial infarction or ventricular tachyarrhythmia within 6 months
    • prolonged QTc greater than or equal to 480 msec (Fridericia correction)
    • ejection fraction less than institutional normal
    • 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 Willebrand s 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03041701

Contacts
Contact: Donna M Bernstein, R.N. (240) 760-6189 db302w@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Christine M Heske, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03041701     History of Changes
Other Study ID Numbers: 170049
17-C-0049
Study First Received: February 2, 2017
Last Updated: July 11, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
ERMS
ARMS
Monoclonal Antibody
YES
RMS

Additional relevant MeSH terms:
Rhabdomyosarcoma
Rhabdomyosarcoma, Alveolar
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Mitogens
Dasatinib
Immunologic Factors
Physiological Effects of Drugs
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 21, 2017