Ipilimumab and Imatinib Mesylate in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01738139
First received: November 28, 2012
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of the combination of ipilimumab and imatinib that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.

Ipilimumab is designed to increase the immune system's ability to fight cancer.

Imatinib is designed to bind to certain proteins on the tumor cells, which may prevent the cells from growing.


Condition Intervention Phase
Advanced Cancers
Drug: Ipilimumab
Drug: Imatinib Mesylate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Ipilimumab and Imatinib Mesylate [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) defined as highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort.


Estimated Enrollment: 96
Study Start Date: February 2013
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab + Imatinib Mesylate
The dose escalation portion of this study will consist of an initial daily oral administration of imatinib mesylate 400 mg alone for 14 days. A single Ipilimumab treatment 1 mg/kg given on day 15 will be added to daily imatinib mesylate therapy. Dose escalation group first study cycle is 35 days. Each cycle after that is 21 days. This study has an expansion cohort using the MTD determined by the dose escalation study to treat patients with KITconfirmed GIST, melanoma, and uncategorized solid tumors. Both studies will consist of a screening visit and continuous 21-day treatment cycles. Cycles will be repeated every 21 days for 4 cycles until disease progression or development of intolerable toxicities, and a post-treatment visit.
Drug: Ipilimumab

Dose Escalation Group Starting Dose: 1 mg/kg by vein on day 15. The first study cycle is 35 days. Each cycle after that is 21 days.

Dose Expansion Group Starting Dose: MTD from Dose Escalation Group.

Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
Drug: Imatinib Mesylate

Dose Escalation Group Starting Dose: 400 mg by mouth once per day for 35 days. The first study cycle is 35 days. Each cycle after that is 21 days.

Dose Expansion Group Starting Dose: MTD from Dose Escalation Group.

Other Names:
  • Imatinib
  • Gleevec
  • STI 571
  • NSC-716051

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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 GIST, melanoma, or uncategorized tumors that are positive for c-KIT mutations. KIT positive tumors will be confirmed in original biopsied tumors and biopsied tumors acquired during this study. This analysis will be done by CLIA approved mutational analysis which will likely include isolation of genomic DNA from tumor, polymerase chain reaction (PCR) amplification of exons of interest of c-KIT gene, bidirectional sequencing of PCR amplicons, and computational analysis of sequences to determine mutation presence or absence.
  2. 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.
  3. Age > or = 15 years
  4. ECOG performance status < 2 (Karnofsky > 60%).
  5. Patients must have normal organ and marrow function as defined below: 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); AST(SGOT)/ALT(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
  6. Patients MUST have recovered from all treatment related toxicities to Grade 1 NCI CTCAE (v 4.0) in severity
  7. Patients must be willing and able to review, understand, and provide written consent before starting therapy
  8. Patients with histologically proven intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma will be eligible. Patients must have shown unequivocal radiographic evidence for tumor progression by 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.

Exclusion Criteria:

  1. 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.
  2. History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
  3. 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.
  4. 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.
  5. Known HIV, Hepatitis B, or Hepatitis C.
  6. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).
  7. 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 (used in the management of cancer or non-cancer-related illnesses).
  8. Patients who do not agree to practice appropriate birth control methods while on therapy.
  9. 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.
  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: NCT01738139

Contacts
Contact: David S. Hong, MD 713-563-1930

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: David S. Hong, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01738139     History of Changes
Other Study ID Numbers: 2012-0784, NCI-2013-00030
Study First Received: November 28, 2012
Last Updated: April 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Advanced Malignancies
Metastatic
Unresectable
Ipilimumab
Yervoy
BMS-734016
MDX010
Imatinib Mesylate
Imatinib
Gleevec
STI 571
NSC-716051

Additional relevant MeSH terms:
Neoplasms
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014