Sunitinib in Treating Patients With Kidney Cancer That Cannot Be Removed by Surgery

A Phase II Study of Sunitinib Malate in Patients With Renal Cell Carcinoma and Unresectable Primary Tumors

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00459979

Enrollment

Registered

2007-04-13

Start date

2007-03-31

Completion date

2013-09-30

Last updated

2014-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Cancer

Keywords

clear cell renal cell carcinoma, stage III renal cell cancer, stage IV renal cell cancer, papillary renal cell carcinoma

Brief summary

RATIONALE: Sunitinib may stop the growth of kidney cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and how well sunitinib works in treating patients with kidney cancer that cannot be removed by surgery.

Detailed description

OBJECTIVES: * To determine the percentage of patients with renal cell carcinoma and unresectable primary tumors who can achieve sufficient tumor response, according to the operating surgeon, to undergo nephrectomy after sunitinib therapy. * To evaluate the safety of sunitinib in patients with renal cell carcinoma and unresectable primary tumors, including analysis of the morbidity of surgery after sunitinib therapy * To evaluate the objective response rate of patients with renal cell carcinoma and unresectable primary tumors who receive sunitinib therapy. OUTLINE: A single arm phase II study of sunitinib in patients with unresectable renal cell carcinoma (RCC) will be conducted, including patients with and without distant metastases. Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity. Surgery is performed if and when primary tumor becomes resectable. Patients with residual and/or metastatic disease may resume sunitinib malate within 8 weeks after surgery. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 31 patients will be accrued for this study.

Interventions

DRUGsunitinib malate

Sunitinib will be dosed at 50 mg p.o. daily

PROCEDUREconventional surgery

nephrectomy

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Histologically or cytologically confirmed renal cell carcinoma (any histology) based on prior biopsy or biopsy performed and reviewed at Cleveland Clinic Foundation. This can include pathology read as adenocarcinoma consistent with renal origin. * Unresectable primary tumor due to any of the following factors or various combinations thereof: * Large tumor size (\> 15 cm) * Bulky lymphadenopathy (\> 4 cm or encasement of renal vessels or great vessels) * Venous thrombosis (high level/invasive disease requiring inferior vena cava reconstruction or hypothermic circulatory arrest) * Proximity to vital structures (e.g., mesenteric vasculature) * Any one of these factors may or may not constitute unresectability, but for consideration for this trial, the surgical and medical oncologist must agree that the particular constellation of findings for the patient under consideration would likely entail a low probability (\<50%) that the tumor would be resectable (with negative margins) or that the potential morbidity associated with an attempt at surgical resection would not be clinically acceptable. The numerical thresholds noted above are only a guideline and the clinical judgment of the surgeon and medical oncologist will determine unresectability. * Patients with history of brain metastases can be enrolled 2 weeks following the completion of gamma knife or whole brain radiotherapy. * ECOG performance status (PS) 0-1 or Karnofsky PS \>/=70% * Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 times upper limit of normal (ULN) * Total Serum Bilirubin ≤ 1.5 times ULN * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 8.0 g/dL (transfusion allowed) * Serum calcium ≤ 12.0 mg/dL * Creatinine ≤ 2.5 mg/dL * Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment * Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion criteria

* The presence of any of the following will exclude a patient from study enrollment: * Prior systemic treatment for RCC. * Evidence of bleeding diathesis or coagulopathy. Patients with hematuria from the primary renal tumor are eligible provided all other eligibility criteria are met. * Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolism. * Hypertension that cannot be controlled by medications to \< 160/90 mmHg. * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. * Pregnancy or breastfeeding. * Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Design outcomes

Primary

Measure	Time frame	Description
Response to Sunitinib Therapy	1 year from start of treatment	Defined as a reduction in tumor burden to such an extent that nephrectomy is permitted within 1 year of the start of therapy. No response to sunitinib therapy is defined as a nephrectomy not being permitted within 1 year of the start of therapy or removal from the study for any reason

Secondary

Measure	Time frame	Description
Progression Free Survival	1 year from start of treatment	Progression free survival is defined as the amount of time (in months) between the start of treatment and documented RECIST defined progression. RECIST progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition to an absolute increase of at least 5mm.
Percent Decrease of Diameter of Primary Tumors	1 year from start of treatment	Median percent decrease in size in all primary renal cell carcinoma tumors. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.
The Number of Patients With Any Type of Complication or Adverse Event	1 year from start of treatment	The safety of sunitinib will be assessed by recording the number of patients with any type of complication or adverse event within 1 year of the start of therapy.
Number of Tumors With 30% Reduction in Size	1 year from start of treatment	Number of tumors with at least 30% reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.
Median Size Reduction Among Tumors With Some Shrinkage	1 year from start of treatment	The median size reduction in the largest diameter of the primary RCC tumor among the tumors with at least some shrinkage in diameter
Number of Tumors Which Decreased in Size	1 year from start of treatment	Number of tumors with at least some reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Sunitinib sunitinib malate : Sunitinib will be dosed at 50 mg p.o. daily conventional surgery : nephrectomy	30
Total	30

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Protocol Violation	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Sunitinib
Age, Continuous Median age	61 Years FULL_RANGE 10
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) White	27 Participants
Region of Enrollment United States	30 participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	21 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	28 / 28
serious Total, serious adverse events	16 / 28

Outcome results

Primary

Response to Sunitinib Therapy

Defined as a reduction in tumor burden to such an extent that nephrectomy is permitted within 1 year of the start of therapy. No response to sunitinib therapy is defined as a nephrectomy not being permitted within 1 year of the start of therapy or removal from the study for any reason