Dasatinib and Ipilimumab in Treating Patients With Gastrointestinal Stromal Tumors or Other Sarcomas That Cannot be Removed by Surgery or Are Metastatic

This study is currently recruiting participants.
Verified December 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01643278
First received: July 16, 2012
Last updated: April 4, 2014
Last verified: December 2013
  Purpose

This phase I trial studies the side effects and best dose of dasatinib and ipilimumab in treating patients with gastrointestinal stromal tumors or other sarcomas that cannot be removed by surgery or are metastatic. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving dasatinib together with ipilimumab may kill more tumor cells.


Condition Intervention Phase
Chondrosarcoma
Clear Cell Sarcoma of the Kidney
Endometrial Stromal Sarcoma
Ewing Sarcoma of Bone
Extraosseous Ewing Sarcoma
Gastrointestinal Stromal Tumor
Mast Cell Sarcoma
Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Metastatic Osteosarcoma
Ovarian Sarcoma
Recurrent Adult Soft Tissue Sarcoma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Osteosarcoma
Recurrent Uterine Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage III Uterine Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Stage IV Uterine Sarcoma
Drug: dasatinib
Biological: ipilimumab
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Dasatinib in Combination With Ipilimumab for Patients With Advanced Gastrointestinal Stromal Tumor and Other Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose defined as the highest dose studied for which the observed incidence of dose-limiting toxicity is less than 33% according to the National Cancer Institute Common Toxicity Criteria [ Time Frame: Up to week 12 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • RR [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Immune related response rate (CR+PR) and Choi criteria will be calculated along with a 95% confidence interval.

  • PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years ] [ Designated as safety issue: No ]
    Will be estimated using Kaplan-Meier methodology.

  • PFS at 6months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Will be estimated using Kaplan-Meier methodology.

  • OS [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be estimated using Kaplan-Meier methodology.


Estimated Enrollment: 39
Study Start Date: July 2012
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dasatinib and ipilimumab)
Patients receive dasatinib PO QD for 7 days. Patients then receive dasatinib PO QD and ipilimumab IV once on weeks 1, 4, 7 and 10. Beginning on week 24, patients then receive dasatinib PO QD and ipilimumab IV once every 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of treatment with ipilimumab in combination with dasatinib in subjects with gastrointestinal stromal tumor (GIST) and other advanced sarcomas.

SECONDARY OBJECTIVES:

I. Response rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, immune-related response criteria, and Choi criteria.

II. Progression free survival (PFS). III. Progression-free survival at 6 months (PFS6months). IV. Overall survival (OS). V. Immunological correlative studies.

OUTLINE: This is a dose-escalation study of dasatinib.

Patients receive dasatinib orally (PO) once daily (QD) for 7 days. Patients then receive dasatinib PO QD and ipilimumab intravenously (IV) once on weeks 1, 4, 7 and 10. Beginning on week 24, patients then receive dasatinib PO QD and ipilimumab IV once every 12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DOSE ESCALATION COHORT: subjects must have histologically or cytologically confirmed sarcoma that is metastatic or unresectable
  • DOSE EXPANSION COHORT: subjects must have histologically or cytologically confirmed GIST that is metastatic or unresectable
  • Patients must have measurable disease per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • DOSE ESCALATION COHORT: patients must have had at least one prior therapy
  • DOSE EXPANSION COHORT: GIST patients must have had progression on or have been intolerant to imatinib and sunitinib
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3 K/mcL
  • Absolute neutrophil count >= 1.5 K/mcL
  • Platelets >= 100 K/mcL
  • Hemoglobin >= 8.0 g/dl
  • Total bilirubin =< 1.5 x institutional upper limit of normal; note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine =< 1.5 x institutional upper limit of normal or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • COHORT EXPANSION ONLY: subjects enrolled in the maximum tolerated dose (MTD) cohort expansion must have accessible tumor that can be biopsied with acceptable clinical risk (as judged by the investigator) and must consent to a pre-treatment, week 0 and week 6 biopsy (following two doses of ipilimumab); an optional biopsy at the time of progressive disease will also be discussed however is not mandatory
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; 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; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of dasatinib administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy (non-tyrosine kinase inhibitor [TKI]) or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients with a history of prior treatment with ipilimumab or dasatinib
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases are excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to dasatinib and ipilimumab
  • Patients who require concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
  • Patients who require concurrent treatment with any medications or substances that have significant proarrhythmic potential are ineligible
  • 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 corrected QT (QTc) > 480 msec
    • Ejection fraction less than 50%
    • Major conduction abnormality (unless a cardiac pacemaker is present)
  • 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
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dasatinib
  • Subjects may not have known human immunodeficiency virus (HIV), active hepatitis A, or hepatitis B or C infection
  • Subjects with any active autoimmune disease or a documented history of autoimmune disease or history of syndrome that required systemic steroids or immunosuppressive medications including but not limited to inflammatory bowel disease, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (e.g. Guillain-Barre syndrome), and multiple sclerosis; patients with vitiligo, asthma and diabetes are NOT excluded; final determination can be left to the discretion of the principal investigator
  • Subjects may not have ongoing chronic diarrhea
  • Subjects may not have had prior organ allograft or allogeneic bone marrow transplantation
  • Subjects may not have any major surgery within 4 weeks
  • Subjects may not have known current drug or alcohol abuse
  • Subjects may not have an underlying medical condition that in the opinion of the investigator could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of dasatinib and ipilimumab in treated subjects
  • Subjects may not have other active malignancies other than indolent malignancies not requiring active therapy which the investigator determines are unlikely to interfere with treatment and safety analysis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01643278

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Richard D. Carvajal    646-888-4161    carvajar@mskcc.org   
Principal Investigator: Richard D. Carvajal         
Sponsors and Collaborators
Investigators
Principal Investigator: Richard Carvajal Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01643278     History of Changes
Other Study ID Numbers: NCI-2012-01165, NCI-2012-01165, CDR0000737378, 12-083, 9172, P30CA008748, U01CA069856
Study First Received: July 16, 2012
Last Updated: April 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mast-Cell Sarcoma
Sarcoma, Endometrial Stromal
Sarcoma, Clear Cell
Sarcoma
Sarcoma, Ewing's
Chondrosarcoma
Osteosarcoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Gastrointestinal Stromal Tumors
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Bone Tissue
Mastocytosis
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Neoplasms, Complex and Mixed
Endometrial Stromal Tumors
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on April 16, 2014