Kidney Cancer
Conditions
Keywords
clear cell renal cell carcinoma, stage IV renal cell cancer
Brief summary
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Infusing irradiated donor lymphocytes into the patient may help the patient's immune system kill tumor cells. Giving sunitinib together with irradiated donor lymphocytes may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sunitinib together with irradiated donor lymphocytes works in treating patients with metastatic kidney cancer.
Detailed description
OBJECTIVES: Primary * Determine progression-free survival of patients with metastatic clear cell renal cell carcinoma treated with sunitinib and irradiated allogeneic lymphocytes. Secondary * Determine rates and kinetics of clinical/radiographic response in these patients. * Determine toxicities associated with treatment in these patients. * Assess stable disease at 6 months in these patients. * Assess overall survival of these patients. OUTLINE: Patients receive oral sunitinib malate once daily for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Beginning with course 2 of sunitinib malate, patients also receive irradiated allogeneic lymphocytes IV over 1 hour every 8-16 weeks for up to 6 infusions in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 60 days.
Interventions
BIOLOGICALtherapeutic allogeneic lymphocytes
Patients with a partially HLA-matched family member who can serve as a hematopoietic stem cell transplant donor will receive partially HLA-matched irradiated donor lymphocytes approximately every 8 weeks depending upon response
DRUGsunitinib malate
Sunitinib will be administered orally at a dose of 50 mg qd for 4 consecutive weeks followed by 2 weeks off for every cycle.
Sponsors
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
Rutgers, The State University of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed renal cell carcinoma * Primary lesion or metastatic site demonstrating clear cell variant with \< 25% of any other histology * Radiographically measurable disease by RECIST criteria * Initiated treatment with sunitinib malate ≤ 6 weeks ago * No radiographically detectable brain metastases by MRI or CT scan * HLA-partially matched related donor available, as determined by serologic and/or DNA typing * Appropriate HLA match (≥ 2/6 HLA A, B, DR match) PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Absolute neutrophil count \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Total bilirubin ≤ 2.0 times upper limit of normal (ULN) * AST ≤ 3.0 times ULN * Calculated creatinine clearance ≥ 40 mL/min * Cardiac ejection fraction ≥ 50% * QTc interval \< 500 msec by EKG * Not pregnant * Negative pregnancy test * Fertile patients must use effective contraception * No known HIV positivity * None of the following within the past 6 months: * Myocardial infarction * Severe/unstable angina * Coronary/peripheral artery bypass graft * Symptomatic congestive heart failure * Cerebrovascular accident or transient ischemic attack * Pulmonary embolism * No ongoing ventricular cardiac dysrhythmias ≥ grade 2, according to NCI CTCAE v3.0 * No history of serious ventricular arrhythmia (e.g., ventricular tachycardia \> 3 beats in a row) * No ongoing atrial fibrillation * No other malignancies within the past 3 years, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, or ductal or lobular carcinoma in situ of the breast * No other concurrent serious illness PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior systemic therapy for metastatic renal cell carcinoma * No prior immunotherapy * No prior VEGF-targeted or mTOR-targeted therapies * No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), St. John's wort, ketoconazole, dexamethasone, dysrhythmic drugs (e.g., terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice * No other concurrent investigational anticancer agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, on average up to 1 year. | Determined as the time from treatment with combination sunitinib with irradiated allogeneic lymphocytes to progressive disease or death whichever occurred first. Progression is determined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0) as 20% increase in the sum of the of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Best responseFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year. | Per response evaluation criteria in solid tumors criteria (RECIST v 1.0) for target lesions and assessed by MRI; Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Stable disease - not meeting criteria for response or progression. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited through the Rutgers Cancer Institute of New Jersey. The study was open to accrual on 02/03/2009 and closed to accrual on 05/07/2013 because of slow accrual.
Pre-assignment details
We are reporting results on 10 eligible patients. Five patients were deemed ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Plus Irradiated Allogeneic Lymphocytes therapeutic allogeneic lymphocytes: Patients with a partially HLA-matched family member who can serve as a hematopoietic stem cell transplant donor will receive partially HLA-matched irradiated donor lymphocytes approximately every 8 weeks depending upon response
sunitinib malate: Sunitinib will be administered orally at a dose of 50 mg qd for 4 consecutive weeks followed by 2 weeks off for every cycle. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study participant's donor was CMV + | 1 |
Baseline characteristics
| Characteristic | Sunitinib Plus Irradiated Allogeneic Lymphocytes |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Progression-free Survival
Determined as the time from treatment with combination sunitinib with irradiated allogeneic lymphocytes to progressive disease or death whichever occurred first. Progression is determined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0) as 20% increase in the sum of the of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, on average up to 1 year.
Population: Study was terminated early due to slow accrual.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib Plus Irradiated Allogeneic Lymphocytes | Progression-free Survival | 137 days |
Secondary
Response Rate
Per response evaluation criteria in solid tumors criteria (RECIST v 1.0) for target lesions and assessed by MRI; Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Stable disease - not meeting criteria for response or progression.
Time frame: Best responseFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib Plus Irradiated Allogeneic Lymphocytes | Response Rate | PR | 3 participants |
| Sunitinib Plus Irradiated Allogeneic Lymphocytes | Response Rate | Progressive Disease | 2 participants |
| Sunitinib Plus Irradiated Allogeneic Lymphocytes | Response Rate | Stable Disease | 5 participants |