Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00353301
First received: July 14, 2006
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: Erlotinib hydrochloride
Drug: Sirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™ (Erlotinib Hydrochloride) and Rapamune™ (Sirolimus) in the Treatment of Metastatic Renal Cell Carcinoma.

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: Physical exam assessments were performed every 4 weeks during the treatment phase. Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks. ] [ Designated as safety issue: No ]
    Time to progression was defined as the time from beginning of therapy until disease progression or death. For subjects who had not progressed at the time of statistical analysis, progression-free survival was censored at the date of their last tumor assessment. Kaplan-Meier method was used to estimate median progression-free survival. Progression was defined as radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (year 2000 version), non-compliance in obtaining scans, unequivocal clinical progression or the initiation of another medication for the treatment of renal cell carcinoma.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks. ] [ Designated as safety issue: No ]
    For all subjects who had not died at the time of statistical analysis, duration of survival will was censored at the date of last contact. Kaplan-Meier methodology was used to estimate the magnitude of the treatment effect as described for progression-free survival.


Enrollment: 25
Study Start Date: July 2006
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib and Sirolimus

Erlotinib hydrochloride (Tarceva) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. During the treatment period, patients will receive single-agent Tarceva, 150 mg/day.

Sirolimus (Rapamune) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.

Drug: Erlotinib hydrochloride
Patients will receive single-agent Tarceva, 150 mg/day
Other Name: Tarceva
Drug: Sirolimus
Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.
Other Name: Rapamune

Detailed Description:

Despite recent advances metastatic renal cell carcinoma remains an incurable condition. Currently available treatment with high-dose interleukin-2 can lead to complete responses in a small minority of selected patients but is markedly toxic and not broadly available. FDA-approved multikinase inhibitors (sorafenib and sunitinib malate) often cause partial and transient tumor regression. There is no standard treatment metastatic renal cell carcinoma for patients whose disease progressed on multikinase inhibitors. The kinase mammalian target of rapamycin (mTOR) is overstimulated in a subset of renal cell carcinomas and other malignancies and can be blocked by sirolimus leading to growth arrest. Erlotinib hydrochloride is a drug that blocks the function of the epidermal growth factor receptor (EGFR), often over expressed in kidney cancer. Sirolimus and EGFR inhibitors and been safely used in combination. In vitro experiments show that erlotinib enhances the sirolimus induced growth impairment in a panel of renal cell carcinoma cells. In the present study patients with metastatic renal cell carcinoma whose disease progressed on multikinase inhibitors will be treated with the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™). This is a single arm trial with no placebo or drug-based control arm

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent to participate in this study.
  • Histological diagnosis of renal cell carcinoma.
  • Age greater or equal 18 years.
  • Eastern Cooperative Oncology Group (ECOG) Performance status of 2 or better.
  • Life expectancy of at least 3 months.
  • Failure or intolerance to previous treatment with Sutent® and/or Nexavar®.
  • Most recent systemic treatment at least 1 month from the beginning of treatment.
  • Most recent local treatment (surgery or irradiation) > 2 weeks from the beginning of treatment.
  • At least one site of measurable disease by CT scan or MRI (RECIST criteria).
  • Baseline hemoglobin >9 g/dl, platelets > 100,000/mm3, absolute neutrophil count (ANC >1500/mm3.

Exclusion Criteria:

  • Previous treatment with Tarceva™, Iressa™, Rapamune™, temsirolimus or everolimus.
  • Untreated metastasis to the central nervous system.
  • Previous solid organ, bone marrow or stem-cell transplant.
  • Known AIDS or HIV infection.
  • Symptomatic or poorly controlled chronic heart failure.
  • Chronic renal failure requiring dialysis on a regular basis.
  • Chronic liver failure.
  • Serum aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), alkaline phosphatase or bilirubin >1.5 x the upper limit of normal for the local laboratory.
  • Pregnant or breast-feeding women.
  • Other invasive malignant diseases within 5 years (other than squamous or basal cell carcinoma of the skin).
  • Inability to provide informed consent
  • Any other serious and/or unstable medical, psychiatric, or other condition considered by the P.I. to preclude safe or reasonably compliant participation in the protocol.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00353301

Locations
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80010
Sponsors and Collaborators
University of Colorado, Denver
Genentech
Investigators
Principal Investigator: Thomas W Flaig, MD University of Colorado, Denver
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00353301     History of Changes
Other Study ID Numbers: 05-1135.cc
Study First Received: July 14, 2006
Results First Received: December 23, 2013
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Carcinoma, Renal Cell
Receptor, Epidermal Growth Factor
mTOR protein
Sirolimus
Erlotinib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sirolimus
Everolimus
Erlotinib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014