Clinical trial NCT00425386: Sunitinib and Erlotinib in Treating Patients With Unresectable or Metastatic Kidney Cancer
Official title: A Dose Escalation Phase II Study of Sunitinib Plus Erlotinib in Advanced Renal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: stage III renal cell cancer
stage IV renal cell cancer
clear cell renal cell carcinoma
recurrent renal cell cancer
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-01-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Erlotinib Hydrochloride When Used in Combination With Sunitinib.
timeFrame: 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
measure: Progression-free Survival at 8 Months
timeFrame: 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
Secondary outcomes:
measure: To Determine the Safety of Sunitinib in Combination With Erlotinib
timeFrame: For the duration of the study, up to 7 years
measure: Median Time to Progression
timeFrame: For the duration of the study, up to 7 years
measure: Proportion of Patients Whose Best Overall Response is Complete Response, Partial Response, Stable Disease, or Progressive Disease
timeFrame: From the start of treatment until the criteria for response is met.
measure: Maximum Percent Change in Tumor Measurement
timeFrame: Baseline through end of study, up to 7 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Salem
country: United States
facility: Salem Hospital
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Christopher W. Ryan, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: Feng Z, Curti BD, Quinn DI, Strother JM, Chen Z, Agnor R, Beer TM, Ryan CW. A Phase II, Single-arm Trial of Sunitinib and Erlotinib in Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2022 Oct;20(5):415-422. doi: 10.1016/j.clgc.2022.04.018. Epub 2022 May 5.