Sunitinib and Irradiated Donor Lymphocytes in Treating Patients With Metastatic Kidney Cancer

Phase II Study of Sunitinib Plus Extended Courses of Irradiated Allogeneic Lymphocytes for Patients With Renal Cell Carcinoma (SPECIAL Trial)

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Cancer
• Intervention / Treatment: Biological: therapeutic allogeneic lymphocytes; Drug: sunitinib malate

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sunitinib plus Irradiated Allogeneic Lymphocytes

Biological: 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; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): February 22, 2014
• Study Completion (Actual): February 22, 2014

Study Registration Dates

• First Submitted: February 27, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (Estimate): March 2, 2009

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; clear cell renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: 0220080220 (Other Identifier: IRB); P30CA072720 (U.S. NIH Grant/Contract); CDR0000635763 (Other Identifier: NCI); 080708 (Other Identifier: Rutgers Cancer Institute of New Jersey)