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Ipilimumab and Imatinib Mesylate in Treating Participants With Metastatic or Unresectable Solid Tumors

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ClinicalTrials.gov Identifier: NCT01738139
Recruitment Status : Recruiting
First Posted : November 30, 2012
Last Update Posted : September 19, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase I trial studies the side effects and best dose of ipilimumab and imatinib mesylate in treating participants with solid tumors that have spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ipilimumab and imatinib mesylate may work better in treating participants with solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Malignant Solid Neoplasm C-KIT Tyrosine Kinase Protein Overexpression Clinical Stage IV Cutaneous Melanoma AJCC v8 Metastatic Gastrointestinal Stromal Tumor Metastatic Malignant Solid Neoplasm Metastatic Melanoma Pathologic Stage IV Cutaneous Melanoma AJCC v8 Unresectable Melanoma Unresectable Solid Neoplasm Drug: Imatinib Mesylate Biological: Ipilimumab Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicity profile of intravenous ipilimumab (Yervoy) administered in combination with oral imatinib mesylate (GLEEVEC) for patients with advanced malignancies that are refractory to standard therapy, relapsed after standard therapy, or have no available standard therapy.

II. To determine the maximum toxic dose (MTD) and dose limiting toxicities (DLT) of ipilimumab and imatinib mesylate combination therapy.

SECONDARY OBJECTIVES:

I. To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy.

II. To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy in KIT confirmed solid tumors.

III. To evaluate the potential predictive role of tumor-associated immune biomarkers for therapy effectiveness.

IV. To evaluate the potential predictive role of therapy associated toxicities with antitumor activity.

OUTLINE: This is a dose-escalation study.

Participants receive ipilimumab intravenously (IV) over 90 minutes on day 1 and imatinib mesylated orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Ipilimumab (Immunotherapy) and Imatinib Mesylate (c-Kit Inhibitor) in Patients With Advanced Malignancies
Actual Study Start Date : February 19, 2013
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2020


Arm Intervention/treatment
Experimental: Treatment (ipilimumab, imatinib mesylate)
Participants receive ipilimumab IV over 90 minutes on day 1 and imatinib mesylate PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Imatinib Mesylate
Given PO
Other Names:
  • CGP 57148
  • CGP57148B
  • Gleevec
  • Glivec
  • STI 571
  • STI-571
  • STI571

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 7 years ]
  2. Maximum tolerated dose (MTD) [ Time Frame: 84 days ]
    MTD determined as the highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. DLT determined by CTCAE v4.0.



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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For dose escalation study, patients must have histological confirmation of solid tumors that is metastatic or unresectable. For expansion cohorts, patients must have metastatic or unresectable gastrointestinal stromal tumor (GIST), melanoma, or uncategorized tumors with tumor biopsies that are positive for c-KIT mutations by polymerase chain reaction (PCR) or immunohistochemistry (IHC). For patients enrolled in the melanoma expansion cohort, only select KIT mutations will be eligible. Patients with mutations in exon 13 V654X, 14 T6701, 17 D816X and all exon 18 mutations will not be eligible for enrollment.
  • Patients who have completed previous therapies 4-weeks prior to (or within 5 drug half lives) enrollment on study. Radiation therapy wash out period will be 2 weeks. This includes an exception of patients with metastatic GIST tumors who are taking maintenance imatinib mesylate therapy. These patients are allowed to remain on imatinib mesylate therapy up to enrollment in this study.
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky > 60%).
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Total bilirubin < or = 2.0 mg/dL. (Does NOT apply to patients with Gilbert's syndrome)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal (patients with liver involvement will be allowed < or = 5.0 X institutional upper normal limit)
  • Serum creatinine < 2.0 mg/dL
  • Patients MUST have recovered from all treatment related toxicities to grade 1 National Center Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version [v] 4.0) in severity.
  • Patients must be willing and able to review, understand, and provide written consent before starting therapy.
  • Patients with histologically proven intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma will be eligible. Patients must have shown unequivocal radiographic evidence for tumor progression by magnetic resonance imaging (MRI) scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required.
  • Patients in the expansion cohort must also agree to participate in the biomarker study. However, patients in the melanoma KIT positive mutant subgroup, patients must agree to participate in the biomarker study and biopsies.
  • Patients must be willing to stay within 2 hours drive of MD Anderson Cancer Center whilst receiving Ipilimumab therapy. Patient must also agree to present to MD Anderson emergency center while on Ipilimumab therapy.

Exclusion Criteria:

  • Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus or autoimmune vasculitis [e.g., Wegener's granulomatosis] are excluded from this study.
  • History of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
  • Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs): e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  • Any non-oncology live vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).
  • Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (when used in the management of cancers other than intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma, or when used to treat non-cancer-related illnesses).
  • Patients who do not agree to practice appropriate birth control methods while on therapy.
  • Pregnant women are excluded from this study. Women of child-bearing potential and men must agree to use contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01738139


Contacts
Contact: David Hong 713-563-1930 dshong@mdanderson.org

Locations
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: David S. Hong    713-563-1930      
Principal Investigator: David S. Hong         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: David Hong M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01738139     History of Changes
Other Study ID Numbers: 2012-0784
NCI-2018-01811 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2012-0784 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: November 30, 2012    Key Record Dates
Last Update Posted: September 19, 2018
Last Verified: September 2018

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

Additional relevant MeSH terms:
Neoplasms
Melanoma
Gastrointestinal Stromal Tumors
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Antibodies, Monoclonal
Imatinib Mesylate
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action