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Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2009
First Received: January 19, 2007   Last Updated: May 27, 2009   History of Changes
Sponsors and Collaborators: Oregon Health and Science University
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00425386
  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 II

Study Type: Interventional
Study Design: Treatment, Open Label
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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of erlotinib hydrochloride [ Designated as safety issue: Yes ]
  • Progression-free survival at 8 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Median time to progression [ Designated as safety issue: No ]
  • Proportion of patients whose best overall response is complete response, partial response, stable disease, or progressive disease [ Designated as safety issue: No ]
  • Maximum percent reduction in tumor measurement [ Designated as safety issue: No ]

Estimated Enrollment: 49
Study Start Date: November 2006
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
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:

  • 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)
  • AST and 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 QTc interval to > 450 msec for males or to > 470 msec for females
  • LVEF normal by 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00425386

Locations
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea     503-494-1080     trials@ohsu.edu    
Providence Cancer Center at Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213-2967
Contact: Clinical Trials Office - Providence Cancer Center at Providenc     503-215-6412        
Sponsors and Collaborators
Oregon Health and Science University
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: Knight Cancer Institute at Oregon Health and Science University ( Christopher W. Ryan )
Study ID Numbers: CDR0000526204, OHSU-2683, OHSU-SOL-06051-LM
Study First Received: January 19, 2007
Last Updated: May 27, 2009
ClinicalTrials.gov Identifier: NCT00425386     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage III renal cell cancer
stage IV renal cell cancer
clear cell renal cell carcinoma
recurrent renal cell cancer

Study placed in the following topic categories:
Erlotinib
Urinary Tract Neoplasm
Kidney Cancer
Urogenital Neoplasms
Urologic Neoplasms
Angiogenesis Inhibitors
Protein Kinase Inhibitors
Recurrence
Carcinoma
Renal Cancer
Urologic Diseases
Sunitinib
Kidney Neoplasms
Carcinoma, Renal Cell
Clear Cell Renal Cell Carcinoma
Kidney Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial

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

ClinicalTrials.gov processed this record on September 02, 2009