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

NCT00782275 | Completed Phase 2 Results DMC

• 1 other identifier: 08-184
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

Brief Summary

This is a single-arm phase II trial evaluating the combination of avastin and temsirolimus in patients with metastatic renal cell cancer (RCC) including both histologically confirmed clear cell (cc) or non-clear cell (ncc) subtypes. Patients must have experienced disease progression or intolerable toxicity with a vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitor (TKI) (e.g. sorafenib, sunitinib, pazopanib). Only 2 prior VEGF therapies are allowed. The purpose of this research study is to evaluate efficacy of the combination against an historical control. 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.

Conditions

Renal Cell Carcinoma; Kidney Cancer

Keywords

RCC; avastin; temsirolimus

Outcome Measures

Primary Outcomes (1)

• 4-month Progression-Free Survival Rate

  4-month progression-free survival rate was defined as the percentage of participants absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

  Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment. Relevant for this endpoint was disease status at 4 months.

Secondary Outcomes (2)

• Objective Response Rate

  Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment; Treatment continued until disease progression or unacceptable toxicity. Median (range) of treatment duration for this study cohort was 5 cycles (1-39) [1 cycle=28days].

• Overall Survival

  Median follow-up for survival in this study cohort is 56 months.

Study Arms (1)

bevacizumab and temsirolimus

EXPERIMENTAL

bevacizumab: given intravenously at a dose of 10mg/kg every 2 weeks (days 1 and 15) temsirolimus: given intravenously at a dose of 25mg weekly on days 1, 8, 15, and 22 1 cycle=28-days There were no dose reductions for bevacizumab allowed. If bevacizumab was held, the same dose would be used if treatment were resumed. If temsirolimus was held, the same or a reduced dose (15mg IV weekly) could be used upon resumption of therapy. Treatment was continued until the development of unacceptable toxicity or progression.

Drug: bevacizumab; Drug: temsirolimus

Interventions

bevacizumab DRUG

Also known as: avastin

bevacizumab and temsirolimus

temsirolimus DRUG

Also known as: torisel

bevacizumab and temsirolimus

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Genentech, Inc.: collaborator
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Vanderbilt Univeristy Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Mahoney KM, Jacobus S, Bhatt RS, Song J, Carvo I, Cheng SC, Simpson M, Fay AP, Puzanov I, Michaelson MD, Atkins MB, McDermott DF, Signoretti S, Choueiri TK. Phase 2 Study of Bevacizumab and Temsirolimus After VEGFR TKI in Metastatic Renal Cell Carcinoma. Clin Genitourin Cancer. 2016 Aug;14(4):304-313.e6. doi: 10.1016/j.clgc.2016.02.007. Epub 2016 Feb 23.

  PMID: 27036973 RESULT

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Bevacizumab; temsirolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: David F. McDermott MD PhD
• Organization: Beth Israel Deaconess Medical Center

dmcdermo@bidmc.harvard.edu

617-632-9262

Study Officials

• David McDermott, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 29, 2008
• First Posted: October 31, 2008
• Study Start: April 1, 2009
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: January 24, 2018
• Results First Posted: December 20, 2017

Record last verified: 2018-01

Locations

US (3)