Temozolomide and Sunitinib Malate in Treating Patients With Stage III or Stage IV Malignant 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: NCT01005472
Recruitment Status : Active, not recruiting
First Posted : November 2, 2009
Last Update Posted : September 14, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving temozolomide together with sunitinib malate may kill more tumor cells.

Phase II was never conducted due to toxicity in phase I.

PURPOSE: This phase I/II trial is studying the side effects and best dose of sunitinib malate when given together with temozolomide and to see how well they work in treating patients with stage III or stage IV malignant melanoma.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: sunitinib malate Drug: temozolomide Phase 1

Detailed Description:



  • Assess the maximum tolerated dose of sunitinib malate when administered concurrently with temozolomide in patients with stage IIIC or IV malignant melanoma. (Phase I)
  • Assess the overall safety of this regimen in these patients. (Phase I)
  • Determine the response rate in patients treated with this regimen. (Phase II) Phase II was never conducted due to toxicity in phase I.


  • Determine the response rate in patients treated with this regimen. (Phase I)
  • Determine the safety and tolerability of this regimen in these patients. (Phase II)
  • Determine the progression-free survival of patients treated with this regimen.
  • Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of sunitinib malate followed by a phase II study.

Patients receive oral sunitinib malate once daily and oral temozolomide once daily on days 1-42. Treatment repeats every 56 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up very 6 months for up to 5 years.

Phase II was never conducted due to toxicity in phase I.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Daily Oral Dosing With Temozolomide and Sunitinib Malate for 6 Weeks of an 8-Week Cycle in Patients With Metastatic and Unresectable Locally-Advanced Malignant Melanoma
Actual Study Start Date : December 1, 2008
Estimated Primary Completion Date : January 31, 2018
Estimated Study Completion Date : January 31, 2019

Arm Intervention/treatment
Experimental: sunitinib malate, temozolomide Drug: sunitinib malate Drug: temozolomide

Primary Outcome Measures :
  1. Maximum tolerated dose of sunitinib malate when administered concurrently with temozolomide (Phase I) [ Time Frame: 6 weeks ]
  2. Overall safety [ Time Frame: 5 years ]
  3. Response rate as assessed by modified RECIST criteria (phase II) [ Time Frame: 5 years ]
    Phase II was never conducted due to toxicity in phase I.

Secondary Outcome Measures :
  1. Response rate as assessed by modified RECIST criteria (Phase I) [ Time Frame: 6 weeks ]
  2. Progression-free survival [ Time Frame: 5 years ]
  3. Overall survival [ Time Frame: 5 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed Stage IIIC unresectable cutaneous or mucosal melanoma with measureable disease or stage IV cutaneous, mucosal or ocular melanoma with measureable disease.
  • ECOG performance status of 0-2
  • age greater than or equal to 18 years
  • ANC ≥ 1,500/µL
  • Platelet count ≥ 100,000/µL
  • Hemoglobin ≥ 10.0 g/dL
  • Creatinine ≤ 2 times upper limit of normal (ULN)
  • Total bilirubin ≤ 2 times ULN
  • LDH ≤ 5 times ULN
  • AST or ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastasis is present)
  • LVEF ≥ 50% on screening ECHO
  • women of childbearing potential must have a negative urine or serum pregnancy test upto 28 days prior to commencement of dosing.
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
  • before study entry , written informed consent must be obtained. Written informed consent must be obtained from patient prior to performing any study related procedures.

Exclusion Criteria

  • pregnant or nursing
  • any following within the past 12 months:
  • Myocardial infarction
  • Severe and/or unstable angina
  • Coronary and/or peripheral artery bypass graft
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Pulmonary embolism
  • ongoing cardiac dysrhythmias ≥ grade 2, according to NCI CTCAE v3.0
  • prolonged QTc interval on baseline EKG
  • uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg despite optimal medical therapy)
  • pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
  • any known clinically uncontrolled infectious disease, including HIV positivity or AIDS-related illness
  • severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results, and, in the judgment of the investigator, would make the patient inappropriate for study entry
  • prior chemotherapy for melanoma, except for chemotherapy given during isolated limb perfusion for stage IIIC disease
  • Prior adjuvant immunotherapy and/or immunotherapy for metastatic disease allowed
  • prior major surgery, radiotherapy, or immunotherapy within 4 weeks of starting therapy
  • treatment with potent CYP3A4 inhibitors 7 days before study dosing
  • treatment with potent CYP3A4 inducers 12 days before study dosing
  • concurrent treatment on another clinical trial (Concurrent participation on supportive care trials or non-treatment trials (e.g., quality-of-life trials) allowed).
  • concurrent chemotherapy, immunotherapy, biological therapy, or investigational drugs
  • concurrent drugs with dysrhythmic potential, including any of the following:
  • Terfenadine
  • Quinidine
  • Procainamide
  • Disopyramide
  • Sotalol
  • Probucol
  • Bepridil
  • Haloperidol
  • Risperidone
  • Indapamide

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): NCT01005472

United States, California
University of California Los Angeles (UCLA)
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Bartosz Chmielowski, MD University of California, Los Angeles

Responsible Party: Jonsson Comprehensive Cancer Center Identifier: NCT01005472     History of Changes
Obsolete Identifiers: NCT00859326
Other Study ID Numbers: CDR0000634373
P30CA016042 ( U.S. NIH Grant/Contract )
10-001406 ( Other Identifier: UCLA IRB )
First Posted: November 2, 2009    Key Record Dates
Last Update Posted: September 14, 2017
Last Verified: September 2017

Keywords provided by Jonsson Comprehensive Cancer Center:
stage III melanoma
stage IV melanoma
recurrent melanoma
ciliary body and choroid melanoma, medium/large size
extraocular extension melanoma
iris melanoma
metastatic intraocular melanoma
recurrent intraocular melanoma

Additional relevant 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
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors