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Phase I Study of the Combination of BAY 43-9006 (Sorafenib) and CCI-779 (Temsirolimus) in Patients With Metastatic Melanoma

Phase 1/Phase 2
18 Years
Not Enrolling
Melanoma, Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma

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Trial Information

Phase I Study of the Combination of BAY 43-9006 (Sorafenib) and CCI-779 (Temsirolimus) in Patients With Metastatic Melanoma


I. To determine the maximum tolerated dose of temsirolimus when administered with sorafenib
in patients with metastatic, recurrent, or unresectable melanoma. (Phase I) II. To determine
the safety and toxicity of this regimen in these patients. (Phase I)


- To Determine the population pharmacokinetics of this regimen in these patients.

- To correlate tumor and blood biomarkers with clinical outcome in patients treated with
this regimen.

OUTLINE: This is a multicenter, phase I, dose-escalation study to be followed by a phase II,
open-label study. (Note: Study progression to phase II did not occur.)

Patients receive temsirolimus intravenous (IV) over 30 minutes on days 1, 8, 15, and 22 and
oral sorafenib once or twice daily on days 1-28. Treatment course repeats every 28 days for
up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months.

Inclusion 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.

- The Eastern Cooperative Oncology Group (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

- No traumatic injury within the past 3 weeks.

- 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 prothrombin time (PT) INR (international normalized ratio) < 1.1 times upper
limit of normal (ULN).

- Unidimensionally measurable disease >= 20 mm by conventional techniques or >= 10 mm
by spiral computed tomography (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.

- White Blood Count (WBC) >= 3,000/mm³

- Absolute neutrophil count >= 1,500/mm³

- Platelet count >= 100,000/mm³

- Serum cholesterol =< 350 mg/dL

- Triglycerides =< 400 mg/dL

- aspartate aminotransferase/alanine aminotransferase (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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of CCI-779 in combination with BAY43-9006 (Phase I)

Outcome Description:

Maximum tolerated dose (MTD) of CCI-779 in combination with BAY43-9006 (Phase I) determined by dose limiting toxicities (DLT) assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) The MTD is defined as the highest dose studied in which the incidence of DLT is < 33%.

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Kevin Kim

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

April 2006

Completion Date:

February 2012

Related Keywords:

  • Melanoma
  • Recurrent Melanoma
  • Stage III Melanoma
  • Stage IV Melanoma
  • Melanoma



M D Anderson Cancer CenterHouston, Texas  77030