Kidney Cancer
Conditions
Keywords
recurrent renal cell cancer, stage IV renal cell cancer, clear cell renal cell carcinoma, papillary renal cell carcinoma, clear cell sarcoma of the kidney
Brief summary
RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth or tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving sunitinib malate and gemcitabine hydrochloride together is more effective than sunitinib malate alone in treating patients with kidney cancer. PURPOSE: This randomized phase II clinical trial is studying giving sunitinib malate together with or without gemcitabine hydrochloride to see how well they work in treating patients with advanced kidney cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary * To evaluate the response rate to sunitinib malate with vs without gemcitabine hydrochloride in patients with advanced renal cell carcinoma with sarcomatoid features. Secondary * To evaluate progression-free survival of these patients. * To evaluate overall survival of these patients. * To describe the toxic effects of both sunitinib malate alone and in combination with gemcitabine hydrochloride in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to risk (good risk \[clear cell and \< 20% sarcomatoid and performance status (PS) 0\] vs intermediate risk \[20-50% sarcomatoid and PS 0\] vs poor risk \[non-clear cell or \> 50% sarcomatoid or PS 1 or non-clear cell\]). Patients are randomized to 1 of 2 treatment arms. * Arm A: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 22, and 29 and oral sunitinib malate once daily on days 1-14 and 22-35. * Arm B: Patients receive oral sunitinib malate once daily on days 1-14 and 22-35. In both arms, courses repeat every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year. ACTUAL ACCRUAL: A total of 87 patients (47 in arm A and 40 in arm B) were accrued to this study.
Interventions
DRUGGemcitabine
Given IV
DRUGSunitinib
Given PO
Sponsors
National Cancer Institute (NCI)
ECOG-ACRIN Cancer Research Group
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed\* renal cell carcinoma of any subtype containing any sarcomatoid features NOTE: \*Patients must have a paraffin-embedded tumor specimen from the kidney or metastatic site available for central review and confirmation of tumor histology * Measurable advanced disease that is not resectable by surgery * Patients with resected or radiated brain metastases or those treated with stereotactic radiation therapy are eligible, provided they have been off steroids for at least 2 weeks * More than 2 weeks since prior radiotherapy and recovered * Previously irradiated lesions must not be the sole site of disease * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9.0 g/dL (transfusions allowed) * Serum creatinine clearance ≥ 30 mL/min * serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times upper limit of normal (ULN; ≤ 5 times ULN in the presence of liver metastases) * Total bilirubin ≤ 1.5 times ULN * Baseline corrected QT interval \< 500 msec on EKG * Able to swallow pills * Negative pregnancy test * Fertile patients must use effective contraception before and during study treatment * More than 2 weeks since prior and no concurrent ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice * Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been disease free for the time period considered appropriate to not interfere with the outcome of this study
Exclusion criteria
* Collecting duct or medullary carcinoma * Prior systemic therapy for metastatic disease. One prior therapeutic regimen with a non-tyrosine kinase inhibitor, such as an mtor inhibitor is allowed. Patients who were randomized to placebo on an adjuvant study are eligible * History of stroke within the past 6 months. * Pregnant or nursing * Clinically significant cardiovascular disease, defined as one of the following: * Uncontrolled hypertension (blood pressure \> 150/100 mm Hg at the time of enrollment); patients with hypertension and BP ≤ 150/100 mm Hg on stable antihypertensive regimen are eligible * History of myocardial infarction or unstable angina within the past 24 weeks * New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris * Peripheral vascular disease ≥ grade II * Ongoing ventricular cardiac dysrhythmias ≥ grade 2 as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 * History of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation \> 3 beats in a row) * Ongoing atrial fibrillation * Pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained at less than or within the normal range with medication * Serious concurrent illness or active infection that would jeopardize the ability of the patient to receive study treatment * Known HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Response | Assessed every 3 months for 2 years and every 6 months for year 3. | Response is defined as either complete response (CR, disappearance of all lesions) or partial response (PR, at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters, or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Assessed every 3 months for 2 years and every 6 months for year 3. | Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is defined as follows: * At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. * Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
| Overall Survival | Assessed every 3 months for 2 years and every 6 months for year 3. | Overall survival is defined as the time from randomization to death or date last known alive. |
Countries
United States
Participant flow
Recruitment details
A total of 87 patients were enrolled between June 17, 2010 and November 12, 2015. The first patient was accrued on September 17, 2010.
Participants by arm
| Arm | Count |
|---|---|
| Arm A (Sunitinib + Gemcitabine) Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 22, and 29 and oral sunitinib malate once daily on days 1-14 and 22-35. Each cycle was 42 days (6 weeks) and was to be repeated for a total of one year. | 45 |
| Arm B (Sunitinib) Patients receive oral sunitinib malate once daily on days 1-14 and 22-35. Each cycle was 42 days (6 weeks) and was to be repeated for a total of one year. | 37 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 7 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Ineligible | 1 | 0 |
| Overall Study | Never started treatment | 1 | 3 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Progression | 24 | 25 |
| Overall Study | Symptomatic deterioration | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Arm B (Sunitinib) | Total | Arm A (Sunitinib + Gemcitabine) |
|---|---|---|---|
| Age, Continuous | 61 years | 61 years | 59 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 76 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 32 Participants | 74 Participants | 42 Participants |
| Sex: Female, Male Female | 13 Participants | 28 Participants | 15 Participants |
| Sex: Female, Male Male | 24 Participants | 54 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 41 / 47 | 31 / 40 |
| other Total, other adverse events | 40 / 46 | 27 / 37 |
| serious Total, serious adverse events | 36 / 46 | 17 / 37 |
Outcome results
Primary
Proportion of Patients With Response
Response is defined as either complete response (CR, disappearance of all lesions) or partial response (PR, at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters, or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits).
Time frame: Assessed every 3 months for 2 years and every 6 months for year 3.
Population: Eligible and treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (Sunitinib + Gemcitabine) | Proportion of Patients With Response | 0.18 proportion of participants |
| Arm B (Sunitinib) | Proportion of Patients With Response | 0.11 proportion of participants |
Secondary
Overall Survival
Overall survival is defined as the time from randomization to death or date last known alive.
Time frame: Assessed every 3 months for 2 years and every 6 months for year 3.
Population: Eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (Sunitinib + Gemcitabine) | Overall Survival | 9.4 months |
| Arm B (Sunitinib) | Overall Survival | 7.8 months |
Secondary
Progression-free Survival
Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is defined as follows: * At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. * Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Assessed every 3 months for 2 years and every 6 months for year 3.
Population: Eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (Sunitinib + Gemcitabine) | Progression-free Survival | 4.5 months |
| Arm B (Sunitinib) | Progression-free Survival | 3.6 months |