Sorafenib and Temsirolimus in Treating Patients With Unresectable or Metastatic Solid Tumors

NCT00255658 | Completed Phase 1

• 7 other identifiers: NCI-2012-03164NCI-7146U01CA069853CTRC-IDD-0512CDR0000446567IDD#05-127146
• Study Type: interventional
• Target: 40
• 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 in treating patients with unresectable or metastatic solid tumors. 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 temsirolimus may kill more tumor cells.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• Maximum tolerable dose (MTD) and recommended dose for phase II determined by dose-limiting toxicities (DLT) graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

  4 weeks

Study Arms (1)

Treatment (sorafenib tosylate, temsirolimus)

EXPERIMENTAL

Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. They also receive oral sorafenib\* twice daily starting on day 8 of course 1. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: \*On the days of the temsirolimus infusion, temsirolimus should be taken concurrently with the morning dose of sorafenib. Cohorts of 3-6 patients receive escalating doses of temsirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 12 patients are treated at the MTD.

Drug: sorafenib tosylate; Drug: temsirolimus; Other: laboratory biomarker analysis

Interventions

sorafenib tosylate DRUG

Given orally

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

Treatment (sorafenib tosylate, temsirolimus)

temsirolimus DRUG

Given IV

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

Treatment (sorafenib tosylate, temsirolimus)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (sorafenib tosylate, temsirolimus)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• ECOG performance status =\< (Karnofsky \>= 60%)
• Predicted life expectancy of greater than 12 weeks
• Leukocytes \>= 3,000 mcL
• Absolute neutrophil count \>= 1,500/mcL
• Hemoglobin \>= 9.0 g/dL
• Platelets \>= 100,000/mcL
• Fasting serum cholesterol =\< 350 mg/dL (9.0 mmol/L)
• Total bilirubin within normal institutional limits
• AST (SGOT)/ALT (SGPT) =\< 2.5 x institutional upper limit of normal (ULN)
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Patients on prophylactic anticoagulation therapy (e.g., low-dose warfarin) are eligible provided their coagulation parameter levels are as follows: INR (International Normalized Ratio of prothrombin time) \< 1.1 x ULN
• Patients on full-dose anticoagulants (e.g., warfarin) with PT INR \> 1.5 are eligible provided that both of the following criteria are met:
• The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
• The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events to =\< grade 1 due to agents administered more than 4 weeks earlier, excluding alopecia
• Patients who have received any investigational compound within the past 28 days; patients may not be receiving any other investigational agents while participating in the study
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006 or CCI-779
• Hypertension with systolic blood pressure of \> 140 mmHg or diastolic pressure \> 90 mmHg; however, patients with well-controlled hypertension are eligible
• Patients must not have any evidence of bleeding diathesis or coagulopathy; patients with PT INR \> 1.5 are excluded, unless the patient is on full dose warfarin
• Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow pills are excluded
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with either of these agents
• HIV-positive patients on combination antiretroviral therapy are ineligible
• Patients undergoing major surgery or sustaining a significant traumatic injury within 21 days prior to treatment are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

Sorafenib; temsirolimus; Sirolimus

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

• Muralidhar Beeram

  Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

  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: November 18, 2005
• First Posted: November 21, 2005
• Study Start: September 1, 2005
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2007
• Last Updated: April 15, 2015

Record last verified: 2013-12

Locations

US (1)