Rapamycin Plus Bevacizumab in Advanced Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00667485
Recruitment Status : Completed
First Posted : April 28, 2008
Last Update Posted : January 17, 2014
Genentech, Inc.
Information provided by (Responsible Party):
University of Chicago

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.

Condition or disease Intervention/treatment Phase
Advanced Cancer Metastatic Cancer Drug: Rapamycin (liquid) Drug: Bevacizumab Drug: Rapamycin (Tablets) Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Rapamycin (Sirolimus) With Bevacizumab in Patients With Advanced Malignancies
Study Start Date : April 2008
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Weekly Rapamcyin
Rapamycin (liquid) taken weekly and Bevacizumab (IV infusion ) once every 3 weeks
Drug: Rapamycin (liquid)
Weekly Rapamycin (liquid) 90mg (dose will be split 45mg on Day 1 and Day 2 of each week)
Other Names:
  • sirolimus
  • Rapamune

Drug: Bevacizumab
Multiple doses (dose depends on time of study entry) given by IV once every 3 weeks
Other Name: Avastin

Experimental: Daily Rapamycin
Daily oral rapamycin (tablets) and Bevacizumab (IV infusion)once every 3 weeks
Drug: Bevacizumab
Multiple doses (dose depends on time of study entry) given by IV once every 3 weeks
Other Name: Avastin

Drug: Rapamycin (Tablets)
Daily oral rapamycin (tablets) - 2 doses will be tested 4mg and 6mg
Other Names:
  • sirolimus
  • Rapamune

Primary Outcome Measures :
  1. Toxicity [ Time Frame: 3 weeks ]

Secondary Outcome Measures :
  1. Response [ Time Frame: 6 weeks ]
  2. Pharmacokinetics [ Time Frame: 3 weeks ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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
  • 18 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
    • total bilirubin less than or equal to 1.5 times the institutional ULN
    • creatinine less than or equal to 1.5 times the institutional ULN

Exclusion Criteria:

  • 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
  • Ongoing illness or medical exclusions, including but not limited to:

    • 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
    • history of organ allograft, bone marrow or peripheral blood stem cell transplant
    • known or suspect allergy to bevacizumab or rapamycin
    • seizure disorder treated with steroid or anticonvulsant therapy
    • thrombotic or embolic events within 6 months of starting study
    • pulmonary hemorrhage/bleeding within 12 weeks of starting study (grade 3 event within 4 weeks of first dose of drug). Patients with a history of pulmonary hemorrhage/bleeding cannot be on full dose anticoagulation.
    • pulmonary fibrosis or interstitial lung disease
    • serious non-healing wound, ulcer or bone fracture
    • Major surgery, open biopsy or a traumatic injury within 4 weeks of starting study drug
    • anticipated need for major surgery while on-study
    • current use of any herbal supplements or rifampin (rifampicin)
    • prior history of hypertensive crisis or hypertensive encephalopathy
    • history of myocardial infarction or unstable angina within 6 months of starting study
    • known CNS disease
    • significant vascular disease
    • symptomatic peripheral vascular disease
    • evidence of bleeding diathesis or coagulopathy
    • core biopsy or other minor surgical procedure (except placement of vascular access device) within 7 days of starting study
    • history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of study start
    • proteinuria at screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00667485

United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Genentech, Inc.
Principal Investigator: Ezra Cohen, MD University of Chicago

Responsible Party: University of Chicago Identifier: NCT00667485     History of Changes
Other Study ID Numbers: 15878B
First Posted: April 28, 2008    Key Record Dates
Last Update Posted: January 17, 2014
Last Verified: January 2014

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors