Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma

Condition(s) targeted: Renal Cell Carcinoma; Kidney Cancer

Intervention: avastin (Drug); temsirolimus (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Beth Israel Deaconess Medical Center

Official(s) and/or principal investigator(s):
David McDermott, MD, Principal Investigator, Affiliation: Beth Israel Deaconess Medical Center

The purpose of this research study is to find out the effects (good and bad) the study treatment has on participants and their cancer. Temsirolimus has been approved by the Food and Drug Administration (FDA) in the treatment of renal cell carcinoma. Avastin has been approved by the FDA for other types of cancers but not renal cell carcinoma.

Official title: A Phase II Trial of Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Estimate the median progression-free survival in patients with metastatic RCC who have progressed on VEGF-targeted tyrosine kinase treated with avastin and temsirolimus

Secondary outcome:

Assess the objective response rate for the combination of avastin and temsirolimus following TKI failure

To estimate the median overall survival for patients treated with avastin and temsirolimus following TKI failure

Detailed description:

- Participants will receive avastin on days 1 and 15 of each 28-day treatment cycle.

They will receive temsirolimus on days 1, 8, 15 and 22 of each cycle.

- During all treatment cycles, participants will have a physical exam, blood tests, and

urine test. An assessment of the tumor by CT (Computerized Tomography) scan will be performed every 8 weeks.

- It is anticipated that participants will be in this research study for 5 years.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Histologically confirmed renal cell carcinoma in either primary or metastatic

lesions. Non-clear histology will be allowed.

- Disease progression on a VEGF-targeted tyrosine kinase inhibitor as the most recent

therapy or have experienced intolerable toxicity so as require discontinuation. Only one prior VEGF-targeted tyrosine kinase inhibitor.

- Must be off of VEGF-targeted tyrosine kinase inhibitor for 2 weeks or greater.

- One measurable lesion which is not curable by standard radiation therapy or surgery.

- The enrolling site must agree to obtain paraffin-embedded tumor blocks or at least 10

unstained, paraffin-embedded slides for submission for correlative studies.

- 18 years of age or older

- ECOG Performance Status of 0 or 1

- Baseline laboratory values as outlined in the protocol

- Life expectancy of greater than 3 months

- No prior malignancy diagnosed within the past three years, other than superficial

basal cell and superficial squamous cell, or carcinoma in situ of the cervix. Exclusion Criteria:

- Known CNS disease, except for treated brain metastases

- Previously treated with avastin or mTOR inhibitors

- Other then VEFG-targeted TKI, patients may only have had prior immunotherapy or

chemotherapy for stage IV disease

- History of allergic reaction to Chinese hamster ovary cell products, other

recombinant antibodies, or compounds of similar chemical or biologic composition to avastin or temsirolimus

- History of bleeding diathesis or coagulopathy. Therapeutic anticoagulants are

allowed

- Patients with clinically significant cardiovascular disease

- Patients receiving enzyme-inducing antiepileptic drugs or any other CYP3A4 inducer

such as rifampin or St. John's wort

- No serious non-healing wound, ulcer or bone fracture

- No uncontrolled intercurrent illness including , but not limited to, ongoing active

infection requiring parental antibiotics or psychiatric illness/social situations that would limit compliance with study requirements

- HIV-positive receiving combination anti-retroviral therapy

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days

prior to study enrollment or anticipation of need for major surgical procedure during the course of the study

- Core biopsy or other minor surgical procedure, excluding placement of vascular access

device, within 7 days prior to enrollment on study

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal

abscess within 6 months prior to study enrollment

- Known hypersensitivity to any component of avastin or temsirolimus

- Life expectancy of less than 12 weeks

- History of hemoptysis within 1 month prior to day 1

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, United States

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

Vanderbilt Univeristy Medical Center, Nashville, Tennessee 37232, United States

Starting date: January 2009
Last updated: January 26, 2015