Rapamycin Plus Bevacizumab in Advanced Cancers

NCT00667485 | Completed Phase 1 DMC

• 2 other identifiers: 15878BAVF4180s
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this trial is to determine the toxicity and maximum dose of rapamycin and bevacizumab given together to subjects with advanced cancers. This study will also look at the pharmacokinetics and antitumor activity of the combination.

Conditions

Advanced Cancer; Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• Toxicity

  3 weeks

Secondary Outcomes (2)

• Response

  6 weeks

• Pharmacokinetics

  3 weeks

Study Arms (2)

Weekly Rapamcyin

EXPERIMENTAL

Rapamycin (liquid) taken weekly and Bevacizumab (IV infusion ) once every 3 weeks

Drug: Rapamycin (liquid); Drug: Bevacizumab

Daily Rapamycin

EXPERIMENTAL

Daily oral rapamycin (tablets) and Bevacizumab (IV infusion)once every 3 weeks

Drug: Bevacizumab; Drug: Rapamycin (Tablets)

Interventions

Rapamycin (liquid) DRUG

Weekly Rapamycin (liquid) 90mg (dose will be split 45mg on Day 1 and Day 2 of each week)

Also known as: sirolimus, Rapamune

Weekly Rapamcyin

Bevacizumab DRUG

Multiple doses (dose depends on time of study entry) given by IV once every 3 weeks

Also known as: Avastin

Daily Rapamycin; Weekly Rapamcyin

Rapamycin (Tablets) DRUG

Daily oral rapamycin (tablets) - 2 doses will be tested 4mg and 6mg

Also known as: sirolimus, Rapamune

Daily Rapamycin

Eligibility Criteria

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

You may qualify if:

• Metastatic or unresectable solid tumor for which standard treatments do not exist or are no longer effective
• Performance status of 0-1
• Measurable or non-measurable disease
• Life expectancy of at least 12 weeks
• No anticipated need of other cancer treatments within the next 4 weeks
• years or older
• Negative pregnancy test for women able to have children, agreement to use a medically accepted birth control method while receiving the study drugs and for at least 2 weeks after stopping, not breast feeding
• Ability to understand and willingness to sign a written informed consent document
• No evidence of bleeding diathesis
• Patients without lung cancer receiving anti-coagulation treatment can participate
• Adequate organ and marrow function:
• ALT and AST less than or equal to 2.5 times the institutional ULN (less than 5 times for patients with liver involvement)
• hemoglobin at least 9g/dL
• absolute neutrophil count at least 1,500/µL
• platelets at least 100,000/µL

You may not qualify if:

• Prior treatment with both bevacizumab and an mTOR inhibitor is not allowed. Prior treatment with both bevacizumab OR mTOR inhibitor (including rapamycin) is allowed. Patients who had a grade 3 or greater side effect with either bevacizumab or an mTOR inhibitor cannot take part in this study.
• Chemotherapy or Immunotherapy within the 4 weeks of study start
• Radiotherapy within 14 days of study start
• Cannot be receiving any other investigational drugs or any other cancer treatments while on study (with the exception of androgen ablating agents for patients with prostate cancer).
• Patients with squamous non-small cell lung cancer (NSCLC)
• Patients with lung cancer or lung metastases:
• on full dose anticoagulation
• taking 325mg aspirin per day
• on non-steroidal anti-inflammatory agents
• HIV positive patients receiving combination anti-retroviral therapy are excluded due to potential for serious infections while taking marrow suppressing agents
• active or ongoing infection
• symptomatic congestive heart failure
• uncontrolled hypertension despite optimal medical management
• cardiac arrhythmia except paroxysmal atrial fibrillation
• psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• University of Chicago: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Sirolimus; Fluid Therapy; Bevacizumab; Tablets

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Ezra Cohen, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 24, 2008
• First Posted: April 28, 2008
• Study Start: April 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: January 17, 2014

Record last verified: 2014-01

Locations

US (1)