Sorafenib and Temsirolimus in Treating Patients With Metastatic, Recurrent, or Unresectable Melanoma

NCT00349206 | Completed Phase 1

• 6 other identifiers: NCI-2009-001312005-0215CDR00004801577149P30CA016672N01CM62202
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of temsirolimus when given together with sorafenib and to see how well they work in treating patients with metastatic, recurrent, or unresectable melanoma. Sorafenib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with temosirolimus may kill more tumor cells.

Conditions

Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of CCI-779 in combination with BAY43-9006 (Phase I) determined by DLT assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

  28 days

• Objective response rate (complete response and partial response) CCI-779 in combination with BAY43-9006 (Phase II)

  Up to 5 years

Secondary Outcomes (3)

• Progression-free survival

  The duration of time from start of treatment to date of first evidence of progression or the date of last follow-up for patients who do not progress, assessed up to 5 years

• Overall survival

  5 years

• Noncompartmental pharmacokinetic parameters of BAY43-9006 and CCI-779 estimated using a validated commercial software

  Week 1 and 3

Study Arms (1)

Arm 1

EXPERIMENTAL

Patients receive temsirolimus IV over 30 minutes on days 1, 8,15, and 22 and oral sorafenib once or twice daily on days 1-28.

Drug: sorafenib tosylate; Drug: temsirolimus

Interventions

sorafenib tosylate DRUG

Given orally

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Arm 1

temsirolimus DRUG

Given IV

Also known as: CCI-779, cell cycle inhibitor 779, Torisel

Arm 1

Eligibility Criteria

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

Criteria: * Histologically or cytologically confirmed melanoma, meeting 1 of the following criteria: recurrent or unresectable stage III disease, stage IV disease, non-choroidal origin. * Tumor must be accessible to biopsy unless appropriate tumor sample collection has occurred within the past 3 months and patient agrees to provide these samples for this study. * ECOG performance status 0-1. * Bilirubin normal * Creatinine normal or creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 30 days after completion of study treatment. * No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib or temsirolimus. * No uncontrolled hypertension, defined as systolic blood pressure \> 140 mm Hg on 2 separate days \< 1 week prior to study entry OR diastolic pressure \> 90 mm Hg on 2 separate days \< 1 week prior to study entry. * No evidence of bleeding diathesis or coagulopathy. * No condition that would impair the ability to swallow pills (e.g., gastrointestinal tract disease resulting in an inability to take oral medication; requirement for IV alimentation; or active peptic ulcer disease). * No uncontrolled illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness or social situations that would limit study compliance. * No traumatic injury within the past 3 weeks. * No more than 1 prior systemic chemotherapy regimen for metastatic melanoma (Phase II). * No prior sorafenib, temsirolimus, or any other agents targeting raf, vascular endothelial growth factor (VEGF)/VEGF receptor, or mTOR (Phase II). * No prior surgical procedures affecting absorption. * At least 3 weeks since prior major surgery. * At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) for melanoma and recovered. * At least 4 weeks since prior radiotherapy and recovered. * Prior biologic or immunotherapeutic regimens allowed. * Prior regional chemotherapy regimens (e.g., isolated limb perfusion) allowed but only 1 prior regional chemotherapy regimen allowed if all target lesions are within the prior regional treatment field. * No concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following: phenytoin, carbamazepine, phenobarbital, rifampin or Hypericum perforatum (St. John's wort). * No concurrent prophylactic hematopoietic colony-stimulating factors. * No other concurrent investigational agents. * No other concurrent anticancer agents or therapies for this cancer. * No concurrent full-dose anticoagulation (i.e., warfarin, IV heparin, or low-molecular weight heparin). * No concurrent grapefruit or grapefruit juice. * No concurrent combination antiretroviral therapy for HIV-positive patients. * Concurrent prophylactic anticoagulation therapy (e.g., low-dose warfarin) allowed provided PT INR \< 1.1 times ULN. * Unidimensionally measurable disease \>= 20 mm by conventional techniques or \>= 10 mm by spiral CT scan (longest diameter to be recorded) and margins of visible cutaneous metastatic lesions should be clearly defined and measured in at least one dimension as \>= 10 mm. * No known brain metastases unless the following criteria are met: no radiographical evidence of recurrences in the brain \>= 3 months after complete resection of the brain metastases, asymptomatic brain metastases stable for \>= 3 months since whole-brain radiation therapy and/or stereotactic radiosurgery and must not require steroid for brain metastases. * WBC \>= 3,000/mm³ * Absolute neutrophil count \>= 1,500/mm³ * Platelet count \>= 100,000/mm³ * Serum cholesterol =\< 350 mg/dL * Triglycerides =\< 400 mg/dL * AST/ALT =\< 2.5 times upper limit of normal. * No peripheral neuropathy \> grade 2. * At least 5 years since prior chemotherapy for other types of cancer.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Sorafenib; temsirolimus; Sirolimus

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; Macrolides; Lactones

Study Officials

• Kevin Kim

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 5, 2006
• First Posted: July 6, 2006
• Study Start: April 1, 2006
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: April 10, 2014

Record last verified: 2013-02

Locations

US (1)