Clinical trial NCT00331409: Everolimus and Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Kidney Cancer
Official title: A Phase II Study of the Mammalian Target of Rapamycin (mTOR) Inhibitor RAD001 in Combination With Imatinib Mesylate in Patients With Previously Treated 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: 2006-05-31
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Everolimus and imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Everolimus may also block blood flow to the tumor. Giving everolimus together with imatinib mesylate may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving everolimus together with imatinib mesylate works in treating patients with metastatic or unresectable kidney cancer.

Detailed description: OBJECTIVES:

Primary

* Estimate the proportion of patients with previously treated metastatic or unresectable clear cell carcinoma of the kidney who are progression free (complete response \[CR\], partial response \[PR\], or stable disease \[SD\]) at 3 months after treatment with everolimus and imatinib mesylate.

Secondary

* Estimate median time to progression in patients treated with this regimen.
* Determine the proportion of patients whose best overall response are CR, PR, SD, or progressive disease.
* Evaluate the mean and range of the maximum percent reduction in tumor size.
* Describe the toxicities of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral imatinib mesylate and oral everolimus once daily beginning on day 1 and continuing in the absence of disease progression.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed clear cell kidney cancer, meeting 1 of the following criteria:

  * Measurable metastatic disease
  * Locally unresectable disease
* No history of known brain metastases that have not been adequately treated with radiotherapy and/or surgery
* Must have received ≥ 1 prior systemic therapy for metastatic or unresectable renal cell carcinoma

PATIENT CHARACTERISTICS:

* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Absolute neutrophil count \> 1,500/mm³
* Platelet count \> 100,000/mm³
* Hemoglobin \> 8 g/dL
* Bilirubin \< 1.5 times upper limit of normal (ULN)
* Serum glutamic oxaloacetic transaminase(SGOT) and Serum glutamic pyruvic transaminase(SGPT) \< 2.5 times ULN
* Creatinine \< 1.5 times ULN
* No New York Heat Association grade III-IV cardiac disease
* No other malignancy within the past 5 years except basal cell skin cancer, cervical carcinoma in situ, or insignificant or inactive disease
* No chronic liver disease (i.e., chronic active hepatitis or cirrhosis)
* No severe or uncontrolled medical disease
* No gastrointestinal disease or impairment that would hinder the absorption of everolimus
* No uncontrolled diabetes
* No chronic renal disease
* No active uncontrolled infection
* No congestive heart failure
* No myocardial infarction within the past 6 months

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 2 weeks since prior major surgery
* More than 4 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin C)
* More than 4 weeks since prior immunotherapy
* More than 4 weeks since other prior investigational agents
* No prior radiotherapy to \> 25% of bone marrow
* No prior treatment with an mammalian target of rapamycin(mTOR) inhibitor
* No concurrent therapeutic warfarin

Primary outcomes:
measure: Progression-free Survival at 3 Months
timeFrame: 3 months post 1st dose
measure: Overall Number of Participants Who Achieve a Response Rate (Complete Response, Partial Response, and Stable Disease) at 3 Months
timeFrame: Up to 4 years
Secondary outcomes:
measure: Median Time to Progression
timeFrame: Time to progression
measure: Number of Subjects That Demonstrated a Reduction in Tumor Measurements.
timeFrame: Up to 4 years
measure: Number of Participants With Adverse Events
timeFrame: Duration of study, Up to 4 years
Other outcomes:
Locations:
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Christopher W. Ryan, MD
role: STUDY_CHAIR
References: