Temozolomide and Sorafenib in Treating Patients With Metastatic or Unresectable Melanoma

NCT00602576 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: CDR000058080806604802514P30CA016520
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 1

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. Sorafenib 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 sorafenib may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different schedules of temozolomide when given together with sorafenib to compare how well they work in treating patients with metastatic or unresectable melanoma.

Conditions

Melanoma (Skin)

Keywords

recurrent melanoma; stage III melanoma; stage IV melanoma

Outcome Measures

Primary Outcomes (1)

• Rate of 6 Month Progression-Free Survival

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  6 months

Secondary Outcomes (2)

• Response Rate

  Approximately 3 years

• Overall Survival Rate

  1 year

Study Arms (4)

Arm A

EXPERIMENTAL

Patients who were temozolomide naive and had no brain metastases received oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42.

Drug: sorafenib tosylate; Drug: temozolomide

Arm B

EXPERIMENTAL

Patients who were temozolomide naive and had no brain metastases received sorafenib tosylate as in arm A and oral TMZ once daily on days 1-5 and 29-33.

Drug: sorafenib tosylate; Drug: temozolomide

Arm C

EXPERIMENTAL

Patient with or without treated brain metastases who were treated with prior temozolomide and progressed were treated with oral sorafenib tosylate twice daily on days -7 to 56 of course 1 and on days 1-56 of all subsequent courses. Patients also receive oral TMZ once daily on days 1-42.

Drug: sorafenib tosylate; Drug: temozolomide

Arm D

EXPERIMENTAL

Patients with treated brain metastases were treated with sorafenib tosylate as in arm B and oral TMZ once daily on days 1-5 and 29-33.

Drug: sorafenib tosylate; Drug: temozolomide

Interventions

sorafenib tosylate DRUG

Given orally

Also known as: nexavar

Arm A; Arm B; Arm C; Arm D

temozolomide DRUG

Given orally

Also known as: temodar

Arm A; Arm B; Arm C; Arm D

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed melanoma that is metastatic or unresectable.
• The following groups are eligible with regard to prior therapy in either the adjuvant or metastatic disease setting:
• a) No prior therapy c) Immunotherapy consisting of Interferon, Interleukin-2 or GM-CSF. d) Chemotherapy, either single-agent or combination. Prior temozolomide is allowable e) Vaccine therapy f) Prior sorafenib is allowable
• NB: There is no limit on the number of prior therapies
• Prior radiation therapy is allowed. However, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions.
• Measurable disease by RECIST criteria. Cutaneous lesions measuring at least 1 cm will be considered. Baseline CT or MRI scans of disease sites must be performed within 4 weeks of study entry. For patients with bone metastases, a baseline bone scan must be performed within 4 weeks of study entry.
• Age \> 18 years.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Baseline laboratory values (evaluated within 14 days of randomization):
• White Blood Count \> 3,000/mm3 Absolute Granulocyte Count \> 1,500/mm3 Platelet Count \> 100,000/mm3 Serum creatinine \< 2.0 x upper limit of normal (ULN) or serum creatinine clearance estimated by the MDRD formula Total Bilirubin \< 1.5 x ULN (\< 3.0 x ULN in the presence of Gilbert's disease AST/ALT \< 2.5 x ULN (\< 5.0 ULN in the presence of liver metastases) INR \< 1.5 and a PTT within the upper limit of normal (if on anticoagulation baseline INR before starting anticoagulation must be \<1.5)
• Patients must have discontinued active immunotherapy (IL-2, interferon, CTLA-4, etc.) or chemotherapy at least 4 weeks prior to entering the study and recovered from adverse events due to those agents. Patients must not receive any other investigational anticancer therapy during the period on study or the four weeks prior to entry, with the exception of vaccines.
• Patients with brain metastases must have completed radiation therapy if radiation is clinically indicated at the time of diagnosis and discontinued steroids prior to enrollment.
• The effects of sorafenib, temozolomide on the developing human fetus are unknown. For this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. If a man impregnates a woman while participatig in this study, he should inform his treating physician immediately as well.

You may not qualify if:

• Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast.
• Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's wort.
• Women must not be pregnant or breast-feeding as the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
• Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded from the study. For patients receiving combination anti-retroviral therapy, the potential impact of pharmacokinetic interactions with sorafenib, temozolomide is unknown. Appropriate studies may be undertaken in patients with HIV and those receiving combination anti-retroviral therapy in the future.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Sorafenib; 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)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Dacarbazine; Triazenes; Imidazoles; Azoles

Results Point of Contact

• Title: Dr. Ravi Amaravadi
• Organization: University of Pennsylvania

ravi.amaravadi@pennmedicine.upenn.edu

2157965159

Study Officials

• Ravi Amaravadi, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 4 arm parallel phase II study Arms A and B are randomized to different schedules of temozolomide Arm C is prior temozolomide-refractory patients Arm D is brain metastases patients

Study Record Dates

• First Submitted: January 25, 2008
• First Posted: January 28, 2008
• Study Start: January 1, 2005
• Primary Completion: December 21, 2008
• Study Completion: July 26, 2009
• Last Updated: June 14, 2022
• Results First Posted: June 14, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)