Clinical Trial: 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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary:

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 wil

Detailed Summary:

Background:

  • Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. The annual incidence in the United States is 4-7 cases per million children under 15 years, which represents 250 new cases per year. Two major histologic subtypes exist: embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS), the latter of which carries a particularly poor prognosis.
  • Over-expression of both the type 1 IGF receptor (IGF-1R) and its ligands has been observed in multiple malignancies, including pediatric sarcomas, and abnormal activation of this pathway contributes to sarcoma development and progression. Downstream signaling cascades of IGF-1R further regulate tumor cell proliferation, survival, and metastasis through the MAPK/ERK and PI3K/mTOR pathways. In the majority of RMS, IGF-1R is highly expressed.
  • Monoclonal antibodies targeting IGF-1R interfere with ligand binding and decrease the expression of the receptor on cell surfaces by internalization and degradation of the receptor. A number of these have been tested in the clinical setting. Results from a phase II trial using monotherapy with monoclonal antibodies against IGF-1R resulted in clinically meaningful responses in about 10-15% of patients with RMS. However, the vast majority of these responses were short-lived with a rapid onset of resistance.
  • YES is a member of the SRC family tyrosine kinases (SFKs), non-receptor tyrosine kinases that function in a number of signaling pathways necessary for cell growth, differentiation and survival. Preclinical work suggests involvement of YES in a number of solid tumor types, including colon carcinoma, oral squamous cell carcinoma, glioma, pancreatic cancer, mesothelioma, and RMS.
  • Recently
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome:

    • 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. ]


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • 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. ]


    Original Secondary Outcome: Same as current

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: February 2, 2017
    Date Started: January 24, 2017
    Date Completion: October 31, 2021
    Last Updated: March 31, 2017
    Last Verified: February 24, 2017