Doxycycline, Temozolomide and Ipilimumab in Melanoma

NCT01590082 | Terminated Phase 1 Results

• 2 other identifiers: 2011-1165NCI-2014-01836
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Keywords

Melanoma; Metastatic Melanoma; Advanced melanoma; Doxycycline; Ipilimumab; Yervoy; MDX010; BMS-734016; Temozolomide; Temodar

Outcome Measures

Primary Outcomes (1)

• Overall Participant Response

  Number of participants with response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Complete Response (CR): Disappearance all target lesions; Any pathological lymph nodes must be \<10mm in short axis. Partial Response (PR): \>30% decrease in sum of diameters of target lesions, reference baseline sum of diameters (e.g. percent change from baseline). Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for progressive disease. Progressive Disease (PD): \>20% increase in sum of diameters of target lesions, reference smallest sum of diameters recorded since treatment started (e.g. percent change from nadir, where nadir defined as smallest sum of diameters recorded since treatment start). In addition, sum must have an absolute increase from nadir of 5mm. Not Applicable (NA): No target lesions at baseline. Not Evaluable (NE): Cannot be classified by 1 of 5 preceding definitions.

  2 cycles, up to 7 weeks

Study Arms (1)

Doxycycline, Ipilimumab, and Temozolomide

EXPERIMENTAL

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; Drug: Ipilimumab; Drug: Temozolomide

Interventions

Doxycycline DRUG

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.

Doxycycline, Ipilimumab, and Temozolomide

Ipilimumab DRUG

Phase I and II: 3 mg by vein on Day 1 of each 21 day cycle for 4 cycles.

Also known as: Yervoy, BMS-734016, MDX010

Doxycycline, Ipilimumab, and Temozolomide

Temozolomide DRUG

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

Also known as: Temodar

Doxycycline, Ipilimumab, and Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be age \>/= 18 years.
• Patients must have histologically or cytologically confirmed diagnosis of malignant (unresectable Stage III or Stage IV) melanoma, not amenable to resection with curative intent.
• 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.
• 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.
• Patients must have evaluable disease for response.
• 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.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1.
• 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
• 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;
• 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.
• 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).
• Patient must be willing and able to sign the informed consent form.
• Patient must be willing and able to self-administer orally and document all doses of doxycycline ingested.
• 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.

You may not qualify if:

• Patients who have received doxycycline or other tetracycline-analogs within the 4 weeks prior to the first dose of the study drug.
• For Phase II portion only, patients with a diagnosis of ocular melanoma will be excluded.
• Patients with an inability to swallow tablets or capsules.
• 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.
• 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.
• Patients with an active second malignancy.
• Patients who are pregnant or breastfeeding.
• 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.
• Patients with history of autoimmune disease.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

Doxycycline; Ipilimumab; Temozolomide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Sapna P. Patel, Associate Professor, Melanoma Medical Oncology
• Organization: The University of Texas (UT) MD Anderson Cancer Center

sppatel@mdanderson.org

(713) 792-2921

Study Officials

• Sapna P. Patel, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: May 2, 2012
• Study Start: November 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: September 2, 2020
• Results First Posted: September 2, 2020

Record last verified: 2020-08

Locations

US (1)