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

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ClinicalTrials.gov Identifier: NCT00425386
Recruitment Status : Completed
First Posted : January 23, 2007
Results First Posted : February 16, 2012
Last Update Posted : May 3, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Christopher Ryan, OHSU Knight Cancer Institute

Tracking Information
First Submitted Date  ICMJE January 19, 2007
First Posted Date  ICMJE January 23, 2007
Results First Submitted Date  ICMJE January 12, 2012
Results First Posted Date  ICMJE February 16, 2012
Last Update Posted Date May 3, 2017
Study Start Date  ICMJE August 2006
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 19, 2015)
  • Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib. [ Time Frame: Participants assessed for DLTs weekly during the first cycle of treatment and every 3 weeks in subsequent cycles until at least one DLT occurs in 33% or more of participants at that dose; participants assessed for the duration of the study, up to 7 years ]
    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 ]
    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).
Original Primary Outcome Measures  ICMJE
 (submitted: January 19, 2007)
  • Maximum tolerated dose of erlotinib hydrochloride
  • Progression-free Survival at 8 Months
Change History Complete list of historical versions of study NCT00425386 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2015)
  • To Determine the Safety of Sunitinib in Combination With Erlotinib [ Time Frame: For the duration of the study, up to 7 years ]
  • Median Time to Progression [ Time Frame: For the duration of the study, up to 7 years ]
    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. ]
  • Maximum Percent Change in Tumor Measurement [ Time Frame: Baseline through end of study, up to 7 years ]
    The maximum percent change in Tumor Measurement is the greatest percent change in longest diameter (LD) for the target lesions from the baseline LD. For patients with no change in LD, the maximum percent change is the lowest increase in LD from the baseline LD.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2007)
  • Safety
  • Median Time to Progression
  • Proportion of Patients Whose Best Overall Response is Complete Response, Partial Response, Stable Disease, or Progressive Disease
  • Maximum Percent Reduction in Tumor Measurement
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer
Official Title  ICMJE A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Kidney Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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

Interventions:
  • Drug: erlotinib hydrochloride
  • Drug: sunitinib malate
  • Procedure: biopsy
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 9, 2011)
60
Original Enrollment  ICMJE
 (submitted: January 19, 2007)
49
Actual Study Completion Date  ICMJE March 2014
Actual Primary Completion Date August 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00425386
Other Study ID Numbers  ICMJE CDR0000526204
P30CA069533 ( U.S. NIH Grant/Contract )
OHSU-2683 ( Other Identifier: Oregon Health & Science University IRB )
OHSU-SOL-06051-LM ( Other Identifier: OHSU Knight Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Christopher Ryan, OHSU Knight Cancer Institute
Study Sponsor  ICMJE OHSU Knight Cancer Institute
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Christopher W. Ryan, MD OHSU Knight Cancer Institute
PRS Account OHSU Knight Cancer Institute
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP