Ipilimumab + Temozolomide in Metastatic Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01119508
First received: May 6, 2010
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

The goal of this clinical research study is to learn if combining ipilimumab and temozolomide can help to control metastatic melanoma. The safety of this drug combination will be studied. Researchers would also like to study how this therapy affects the levels of certain chemicals in the blood that are related to your immune system.


Condition Intervention Phase
Metastatic Melanoma
Drug: Ipilimumab
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Ipilimumab Plus Temozolomide in Patients With Metastatic Melanoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 6-Month Progression-Free Survival (PFS) Rate [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    Progression-free survival estimated using method of Kaplan-Meier. PFS determined from the start of study until disease progression or death, whichever is first. All patients who do not have a disease progression or death censored on their last evaluable tumor assessment date. PFS rate at 6 month provided with its 95% confidence interval estimated using bootstrap method. Median PFS reported together with a two-sided 95% CI calculated using method of Brookmeyer and Crowley. Cox's proportional hazard model used to determine the relationship with PFS and the potential prognostic factors. Exploratory logistic regression used to identify prognostic factors that are significantly correlated with PFS rate at 6 months.


Estimated Enrollment: 64
Study Start Date: May 2010
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ipilimumab + Temozolomide
Induction: Ipilimumab 10 mg/kg IV over 90 minutes Day 1 + Temozolomide 200 mg/m2 PO on Days 1 - 4, every 3 weeks for 4 courses over 3 months.
Drug: Ipilimumab
Induction Phase: 10 mg/kg by vein (IV) over approximately 90 minutes on Day 1 only repeated every 3 weeks until 4 courses of therapy are given over 3 months. For the Maintenance Phase, dose repeated every 12 weeks.
Other Names:
  • BMS-734016
  • MDX010
Drug: Temozolomide
Induction Phase, 200 mg/m^2 by mouth (PO) on Days 1 to 4, repeated every 3 weeks until 4 courses of therapy are given over 3 months. For the Maintenance Phase, dose delivered on Days 1 to 5, repeated every 4 weeks.
Other Name: Temodar

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with histologically documented diagnosis of advanced/inoperable metastatic melanoma of skin or mucosal origin are eligible, provided they fulfill the following conditions:
  2. They are 18 years old to 75 years old with measurable (at least 1 cm) metastatic disease.
  3. They have ECOG performance status of 0 or 1.
  4. Must be at least 21 days since surgery, radiation therapy and 6 weeks after immunotherapy with regimens including vaccine, interferon, IL-2 etc. and fully recovered from adverse effects of these therapies.
  5. Must agree not use vaccines for the treatment of cancer or prevention of disease unless indicated as a component of the protocol regimen (including those for common medical conditions) for up to one month pre and post dosing with ipilimumab.
  6. Required values for initial laboratory tests: WBC: 2000/uL or greater, ANC: 1000/uL or greater, Platelets: 100 x 103/uL or greater, Hemoglobin: 9 g/dL or greater, Creatinine: </=1.5 mg/dL, AST and ALT: </= 2.5 x ULN for subjects without liver metastasis or, </= 5 X UNL for liver metastases, Bilirubin: </= 1.5 mg/dL, LDH </= 2 X UNL
  7. They have no significant intercurrent illness such as a serious infection which requires intravenous antibiotics. No active or chronic infection with HIV, Hepatitis B, or Hepatitis C. No significant psychiatric illness, which includes any life threatening psychiatric illness that has not been adequately controlled despite intervention (with or without medication) despite 6 months of therapy. They should have no GI tract metastasis or bleeding, no autoimmune disease.
  8. They have not been previously exposed to any cytotoxic drugs, targeted therapies or anti CTLA 4 drugs for metastatic melanoma. Patients that received interferon for melanoma in the adjuvant setting are eligible. Prior radiation therapy for metastatic melanoma is permitted provided the patient has unirradiated metastatic sites for response evaluation and any toxicity has returned to baseline.
  9. Patients with brain metastases who have been treated with craniotomy and resection or stereotactic radiosurgery of all symptomatic brain metastases are eligible provided they are 4 weeks from the procedures, MRI/CT of the brain performed within 3 weeks from registration fails to show new metastases and they are off of steroids for at least 2 weeks. Patients previously treated with whole brain radiotherapy are eligible if they are without tumor progression in the brain at least 8 weeks from completion of radiotherapy and are asymptomatic. They should be off steroid therapy for at least 2 weeks.
  10. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject.
  11. (Continued 10) WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as: 1) Amenorrhea 12 consecutive months without another cause, or 2) For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level 35 mIU/mL.
  12. (Continued 11) Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.
  13. Men should use condoms while participating in this study.
  14. must agree not to use vaccines for the treatment of cancer or prevention of disease unless indicated as a component of the protocol regimen (including those for common medical conditions) for up to one month pre and post dosing of ipilimumab.

Exclusion Criteria:

  1. Patients with Uveal melanoma. Patients with skin or mucosal melanoma who are younger than 18 years or more than 75 years of age and those with an ECOG performance status of 2, 3 or 4, or patients without measurable metastases.
  2. Patients with prior cytotoxic, targeted therapy or anti-CTLA 4 drugs for metastatic disease.
  3. Patients with significant cardiac illness such as symptomatic coronary artery disease or previous history of myocardial infarction, impaired left ventricle function or serious cardiac arrhythmias requiring therapy. Borderline cases must be discussed with the PI.
  4. Patients with significant impairment of pulmonary function on account of chronic bronchitis or chronic obstructive pulmonary disease (COPD). Pulmonary function test with the results FEV1 <65% or FVC <65% of predicted. Borderline cases must be discussed with the PI.
  5. Patients on corticosteroids or any other type of immunosuppressive agent (e.g., methotrexate, chloroquine, azathioprine, cyclophosphamide) at time of enrollment only.
  6. Patients with history of second malignancies such as basal cell carcinoma, squamous cell carcinoma and carcinoma in situ of cervix are eligible for therapy. Patients with history of other types of cancers, are eligible provided that they have been free of recurrence from second malignancy for at least 3 years. Each case must be discussed with the PI prior to registration.
  7. Patients with symptomatic uncontrolled brain metastasis that is associated with significant brain edema requiring steroid therapy. Patients will be evaluated by the principal investigator or his designee. Patients with spinal cord metastasis or meningeal carcinomatosis.
  8. WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy. Acceptable contraceptive methods are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy).
  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: NCT01119508

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Investigators
Principal Investigator: Sapna P. Patel, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01119508     History of Changes
Other Study ID Numbers: 2009-0408, NCI-2011-00565
Study First Received: May 6, 2010
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced
Inoperable
Melanoma
Ipilimumab
MDX010
BMS-734016
Temozolomide
Temodar
TMZ
skin
mucosal

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014