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Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00425386
First received: January 19, 2007
Last updated: July 26, 2014
Last verified: July 2014
  Purpose

RATIONALE: Sunitinib and erlotinib may stop the growth of tumor cell by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying the best dose of erlotinib when given together with sunitinib and to see how well they work in treating patients with unresectable or metastatic kidney cancer.


Condition Intervention Phase
Kidney Cancer
Drug: erlotinib hydrochloride
Drug: sunitinib malate
Procedure: biopsy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib. [ Time Frame: Evaluated at each dose level for the duration of the study. ] [ Designated as safety issue: Yes ]
    The MTD is defined as the dose that produces dose limiting toxicity (DLT) in 33% of the patients.

  • Progression-free Survival at 8 Months [ Time Frame: 8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney ] [ Designated as safety issue: No ]
    Defined as the proportion of patients who are progression free (CR, PR and SD) at 8 months after initiating treatment with sunitinib in combination with erlotinib in patients with metastatic or unresectable clear cell or papillary carcinoma of the kidney. Complete Response (CR)= disappearance of all target lesions, Partial Response (PR)= At least a 30% decrease in the sum of the longest diameter of target lesions, and Stable Disease (SD)= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (20% increase in the sum).


Secondary Outcome Measures:
  • To Determine the Safety of Sunitinib in Combination With Erlotinib [ Time Frame: For the duration of the study. ] [ Designated as safety issue: Yes ]
  • Median Time to Progression [ Time Frame: For the duration of the study ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used to estimate the median time to progression.

  • Proportion of Patients Whose Best Overall Response is Complete Response, Partial Response, Stable Disease, or Progressive Disease [ Time Frame: From the start of treatment until the criteria for response is met. ] [ Designated as safety issue: No ]
  • Maximum Percent Reduction in Tumor Measurement [ Time Frame: Baseline through end of study ] [ Designated as safety issue: No ]
    The maximum percent reduction in Tumor Measurement is the greatest percent reduction in longest diameter (LD) for the target lesions from the baseline LD. For patients with no reduction in LD, the maximum percent reduction is the lowest increase in LD from the baseline LD.


Enrollment: 60
Study Start Date: August 2006
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib and Sunitinib

Drug: erlotinib hydrochloride Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily;

  1. 100 mg/day, continuous daily; 1.5= 125 mg/day, continuous daily;
  2. 150 mg/day, continuous daily

Drug: sunitinib malate Will be administered at 50 mg daily, 4 weeks on, 2 weeks off

Drug: erlotinib hydrochloride

Dose Level 0 = 50 mg/day, continuous daily; 0.5= 75 mg/day, continuous daily;

  1. 100 mg/day, continuous daily; 1.5= 125 mg/day, continuous daily;
  2. 150 mg/day, continuous daily
Drug: sunitinib malate
Will be administered at 50 mg daily, 4 weeks on, 2 weeks off
Procedure: biopsy
Paraffin block (or unstained slides) of the primary tumor and/or metastatic lesions (as available) and a plasma sample for future correlative studies will be collected. A paraffin block (or at least 10 unstained slides, each of 10 micromillimeter thickness) from the original paraffin-embedded biopsy material taken at the diagnosis will be stored at 4 degrees Celsius.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of erlotinib hydrochloride when administered with sunitinib malate in patients with unresectable or metastatic renal cell carcinoma.
  • Determine the 8-month progression-free survival of patients treated with this regimen.

Secondary

  • Determine the safety of sunitinib malate and erlotinib hydrochloride in these patients.
  • Determine the duration of response in these patients.
  • Determine the proportion of patients whose best overall response is complete response, partial response, stable disease, or progressive disease.
  • Determine the overall survival of patients treated with this regimen.
  • Determine the maximum percent reduction in tumor measurement in patients treated with this regimen.
  • Collect blood and tissue from these patients for future correlative studies.

OUTLINE: This is an open-label, multicenter, dose-escalation study of erlotinib hydrochloride.

Patients receive oral sunitinib malate once daily on days 1-28 and oral erlotinib hydrochloride once daily on days 1-42. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 33% of patients experience dose-limiting toxicity. Once the MTD is determined, patients are treated with erlotinib hydrochloride at the MTD and sunitinib malate.

Patients undergo blood and tumor specimen collection periodically during study for future correlative studies.

PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed renal cell carcinoma with a component of clear cell or papillary carcinoma

    • Unresectable or metastatic disease (radiologically or clinically confirmed)
  • Measurable disease (≥ 1 site)
  • No known brain metastasis that has not been adequately treated with radiotherapy and/or surgery

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • No grade 3 hemorrhage within the past 4 weeks
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times ULN (< 5 times ULN if due to underlying disease)
  • No chronic liver disease (i.e., chronic active hepatitis or cirrhosis)
  • Creatinine ≤ 1.5 times ULN
  • None of the following cardiovascular conditions within the past 12 months:

    • Myocardial infarction
    • Severe/unstable angina
    • Coronary/peripheral artery bypass graft
    • Symptomatic congestive heart failure
    • Cerebrovascular accident or transient ischemic attack
    • Pulmonary embolism
    • Ongoing cardiac dysrhythmia ≥ grade 2
    • Atrial fibrillation of any grade
    • Prolongation of the corrected QT (QTc) interval to > 450 msec for males or to > 470 msec for females
  • Left Ventricular Ejection Fraction (LVEF) normal by Multigated Acquisition (MUGA) or echocardiogram
  • No hypertension uncontrolled with medical therapy
  • No other active malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ
  • No uncontrolled adrenal insufficiency
  • No uncontrolled hypothyroidism
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)
  • No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs
  • No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 4 weeks since prior major surgery
  • More than 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior radiotherapy
  • No prior radiotherapy to > 25% of the bone marrow
  • More than 28 days since prior investigational agents
  • No prior sunitinib malate
  • No prior anti-epidermal growth factor receptor therapy (e.g., erlotinib hydrochloride, panitumumab, cetuximab, or gefitinib)
  • No concurrent therapeutic warfarin

    • Low-dose oral warfarin ≤ 2 mg daily for deep vein thrombosis prophylaxis is allowed after the maximum tolerated dose of erlotinib hydrochloride is determined
  • No concurrent Hypericum perforatum (St. John's wort)
  • No concurrent chemotherapy or biologic therapy
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00425386

Locations
United States, California
University of Southern California
Los Angeles, California, United States
United States, Oregon
OHSU Knight Cancer Institute
Portland, Oregon, United States, 97239-3098
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, United States, 97213-2967
Salem Hospital
Salem, Oregon, United States, 97301
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Study Chair: Christopher W. Ryan, MD OHSU Knight Cancer Institute
  More Information

Additional Information:
Publications:
Ryan CW, Curti BD, Pattee KJ, et al.: A dose-escalation phase II study of sunitinib (S) plus erlotinib (E) in advanced renal carcinoma (RCC). [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-361, 2008.

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00425386     History of Changes
Other Study ID Numbers: CDR0000526204, P30CA069533, OHSU-2683, OHSU-SOL-06051-LM
Study First Received: January 19, 2007
Results First Received: January 12, 2012
Last Updated: July 26, 2014
Health Authority: United States: Federal Government

Keywords provided by OHSU Knight Cancer Institute:
stage III renal cell cancer
stage IV renal cell cancer
clear cell renal cell carcinoma
recurrent renal cell cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Kidney Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Erlotinib
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014