Working… Menu

Doxycycline, Temozolomide and Ipilimumab in Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01590082
Recruitment Status : Terminated (Accrual slow due to alternate trials and treatment options.)
First Posted : May 2, 2012
Last Update Posted : November 13, 2015
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of doxycycline that can be combined with temozolomide and ipilimumab in patients with advanced melanoma. The safety and level of effectiveness of the study drug combination will also be studied.

Doxycycline is designed to treat bacterial infection. It also blocks a protein called iNOS that is important in tumor cell growth, which may slow the growth of or kill cancer cells.

Temozolomide is designed to stop cancer cells from making new DNA (the genetic material of cells). This may stop the cancer cells from dividing into new cells.

Ipilimumab is designed to block the activity of cells that decrease the immune system's ability to fight cancer.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Doxycycline Drug: Ipilimumab Drug: Temozolomide Phase 1 Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I / II Study of the Combination of Doxycycline With Temozolomide and Ipilimumab in Patients With Metastatic Melanoma
Study Start Date : November 2012
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Arm Intervention/treatment
Experimental: Doxycycline + Ipilimumab + Temozolomide
Doxycycline to start on day -6 of Cycle 1 (1 week before Day 1 of Cycle 1 starts) twice a day until morning of Day 1 of Cycle 1. After the Day 1 of Cycle 1, participants receive first dose of Ipilimumab, and evening of same day, Temozolomide received by mouth once a day for 4 days. Doxycycline administration will continue twice daily for rest of cycle without interruption; Cycle 1 is 4 weeks of treatment. Starting Cycle 2, Doxycycline with temozolomide and ipilimumab administration start on Day 1. Each cycle is 3 weeks. 4 cycles of therapy given over a 3 month period to complete induction phase. After induction therapy, participants continue on Doxycycline.
Drug: Doxycycline

Phase I Starting Dose: 200 mg by mouth twice a day on Day -6 of Cycle 1 (1 week before Day 1 of Cycle 1 starts)

Phase II Starting Dose: Maximum Tolerated Dose (MTD) from Phase I.

Drug: Ipilimumab
Phase I and II: 3 mg by vein on Day 1 of each 21 day cycle for 4 cycles.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010

Drug: Temozolomide
Phase I and II: 200 mg/m2 by mouth on Days 1 - 4 of each 21 day cycle for 4 cycles.
Other Name: Temodar

Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 2 cycles ]
    Overall survival (OS) and time to progression (TTP) calculated using Kaplan-Meier method. Overall response rate at end of study also calculated. Response rate calculated using point estimate, together with 95% confidence interval (CI). Kaplan-Meier method used to estimate progression free survival (PFS) time. PFS defined as time interval between start of treatment to date of disease progression, or death. Response Evaluation Criteria in Solid Tumors ( RECIST) version 1.1 used to evaluate response rate.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patient must be age >/= 18 years.
  2. Patients must have histologically or cytologically confirmed diagnosis of malignant (unresectable Stage III or Stage IV) melanoma, not amenable to resection with curative intent.
  3. Patients must have metastatic melanoma which has >25% of melanoma cells stained positive for iNOS expression by chemiluminescence immunoassay analyzer (CLIA)-certified immunohistochemistry assay. However, in phase I portion of the study, the requirement of >25% of melanoma cells stained positive for iNOS expression does not apply.
  4. Patients must be at least 21 days since surgery, radiation therapy and 6 weeks after immunotherapy with regimens including vaccines, interferon, IL-2, etc. and fully recovered from adverse effects of these therapies.
  5. Patients must have evaluable disease for response.
  6. There is no limit on the number of prior therapies for Phase I portion. For Phase II portion only, patients may have received less than or equal to 1 prior chemotherapy regimen for metastatic melanoma. There is no limit on prior immunotherapies or kinase inhibitors. Patients with prior ipilimumab therapy will be excluded during the phase II portion.
  7. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1.
  8. Patient must have adequate liver and renal function as documented by the following laboratory test results within 14 days prior to starting therapy: • total bilirubin less than or equal to 1.5 x upper limit of normal (ULN); • AST (SGOT) and ALT (SGPT) less than or equal to 2.5 X ULN or less than or equal to 5 X ULN if liver metastasis is present; • serum creatinine less than or equal to 1.2 X ULN
  9. Patient must have adequate bone marrow function as documented by the following laboratory test results within 14 days prior to starting therapy: • platelets greater than 100,000/mm3; • absolute neutrophil count (ANC) greater than 1500/mm3; • hemoglobin greater than 9.0 g/dL;
  10. Patient must have completed any prior chemotherapy, immunotherapy, radiation therapy, biological therapy, or other investigational cancer therapy at least 4 weeks prior to starting the study drug(s) and must have recovered from all acute side effects (to Common Toxicity Criteria for Adverse Effects (CTCAE) less than Grade 1) prior to initiation of the study drug(s). Patients who were receiving mitomycin C or nitrosoureas must be 6 weeks from the last administration of chemotherapy. For a prior BRAF inhibitor, the washout period is 7 days.
  11. Patient (man or woman) must agree to practice effective contraception during the entire study period, unless documentation of infertility exists, and for at least 4 weeks after the last dose of the study drug(s).
  12. Patient must be willing and able to sign the informed consent form.
  13. Patient must be willing and able to self-administer orally and document all doses of doxycycline ingested.
  14. Patients must be willing to have iNOS expression assay test done on disease easily amenable to biopsy or suitable tissue obtained within the last 3 months.

Exclusion Criteria:

  1. Patients who have received doxycycline or other tetracycline-analogs within the 4 weeks prior to the first dose of the study drug.
  2. For Phase II portion only, patients with a diagnosis of ocular melanoma will be excluded.
  3. Patients with an inability to swallow tablets or capsules.
  4. Patients with a symptomatic malabsorptive disorder (eg, Crohn's Disease) or removal of either the terminal ileus or more than 2/3 of the small intestine.
  5. Patients with active brain metastases or primary central nervous system (CNS) malignancies; patients with previously treated brain metastasis may be included, provided that no requirement for steroids and no evidence of progression for greater than or equal to 8 weeks after a local brain treatment.
  6. Patients with an active second malignancy.
  7. Patients who are pregnant or breastfeeding.
  8. Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to:uncontrolled diabetes;active or uncontrolled infection; acute or chronic liver disease (i.e., hepatitis, cirrhosis);confirmed diagnosis of HIV infection; or, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia.
  9. Patients with history of autoimmune disease.

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 identifier (NCT number): NCT01590082

Layout table for location information
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Sapna P. Patel, MD M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01590082     History of Changes
Other Study ID Numbers: 2011-1165
NCI-2014-01836 ( Registry Identifier: NCI CTRP )
First Posted: May 2, 2012    Key Record Dates
Last Update Posted: November 13, 2015
Last Verified: November 2015
Keywords provided by M.D. Anderson Cancer Center:
Metastatic Melanoma
Advanced melanoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents