Stereotactic Body Radiation Therapy and T-Cell Infusion in Treating Patients With Metastatic Kidney Cancer

Phase 1

Terminated

• Conditions: Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage IV Renal Cell Cancer
• Interventions: Radiation: stereotactic body radiation therapy; Drug: cyclophosphamide; Biological: therapeutic autologous lymphocytes; Other: laboratory biomarker analysis

• Registration Number: NCT01943188
• Lead Sponsor: Stanford University

Brief Summary

This pilot phase I trial studies the side effects and best way to give stereotactic body radiation therapy and T-cell infusion in treating patients with metastatic kidney cancer. Giving total body irradiation before a T-cell infusion stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. Chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the radiation therapy.

Detailed Description

PRIMARY OBJECTIVES:

I. Conduct a safety and feasibility study of stereotactic radiotherapy with autologous T-cell infusion for patients with metastatic renal cell carcinoma.

SECONDARY OBJECTIVES:

I. Determine the progression free survival at one year. II. Determine the overall survival at one year.

OUTLINE:

STEREOTACTIC BODY RADIATION THERAPY (SBRT): Patients undergo standard of care SBRT over 1-2 weeks according to tumor volume and location.

LYMPHODEPLETION: Beginning 3 weeks later, patients receive cyclophosphamide orally (PO) twice daily (BID) for 3 days.

REINFUSION OF PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC): Within 3-14 days of completing lymphodepletion with cyclophosphamide, patients undergo autologous PBMC infusion.

After completion of study treatment, patients are followed up at 1 week, 4 weeks, and monthly thereafter.

Study Timeline

• Study First Submitted: 2013-09-11
• Study First Submitted QC: 2013-09-11
• Study First Posted: 2013-09-16
• Study Start: 2014-05
• Primary Completion: 2016-03
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-13
• Last Update Posted: 2017-03-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Histologically confirmed carcinoma of the kidney (clear-cell predominance)
• Have had at least 2 prior systemic treatments for renal cell carcinoma (RCC)
• Have at least 1 extracranial metastasis that is amenable to radiation and at least 1 other site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST)
• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Absolute neutrophil count (ANC) >= 0.75 x 10^9/L
• Absolute lymphocyte count (ALC) >= 0.5 X 10^9/L
• Hemoglobin >= 8 g/dL
• Platelets >= 50 X 10^9/L
• Total bilirubin =< 3 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 X ULN
• Serum creatinine =< 2.1 X ULN (or creatinine clearance of > 50 cc/min)

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Exclusion Criteria

• History of other malignancies within 5 years prior to enrollment except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma, squamous-cell carcinoma of the skin, carcinoma in situ of the cervix, early-stage bladder cancer, or low-grade endometrial cancer

  • Malignancies that have undergone a putative surgical cure (i.e., localized prostate cancer post-prostatectomy) within 5 years prior to enrollment may be discussed with the lead primary investigator

• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for more than 1 week within 6 months prior enrollment

• Presence of uncontrolled infection

• Evidence of active bleeding or bleeding diathesis; any medical condition requiring systemic anticoagulation (including anti-platelet agents)

• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to procedures

• Pregnant and breastfeeding women are excluded; as well as women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the duration of the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (SBRT, autologous PBMC infusion)	stereotactic body radiation therapy	SBRT: Patients undergo standard of care SBRT over 1-2 weeks according to tumor volume and location. LYMPHODEPLETION: Beginning 3 weeks later, patients receive cyclophosphamide PO BID for 3 days. REINFUSION OF PBMC: Within 3-14 days of completing lymphodepletion with cyclophosphamide , patients undergo autologous PBMC infusion.
Treatment (SBRT, autologous PBMC infusion)	therapeutic autologous lymphocytes	SBRT: Patients undergo standard of care SBRT over 1-2 weeks according to tumor volume and location. LYMPHODEPLETION: Beginning 3 weeks later, patients receive cyclophosphamide PO BID for 3 days. REINFUSION OF PBMC: Within 3-14 days of completing lymphodepletion with cyclophosphamide , patients undergo autologous PBMC infusion.
Treatment (SBRT, autologous PBMC infusion)	laboratory biomarker analysis	SBRT: Patients undergo standard of care SBRT over 1-2 weeks according to tumor volume and location. LYMPHODEPLETION: Beginning 3 weeks later, patients receive cyclophosphamide PO BID for 3 days. REINFUSION OF PBMC: Within 3-14 days of completing lymphodepletion with cyclophosphamide , patients undergo autologous PBMC infusion.
Treatment (SBRT, autologous PBMC infusion)	cyclophosphamide	SBRT: Patients undergo standard of care SBRT over 1-2 weeks according to tumor volume and location. LYMPHODEPLETION: Beginning 3 weeks later, patients receive cyclophosphamide PO BID for 3 days. REINFUSION OF PBMC: Within 3-14 days of completing lymphodepletion with cyclophosphamide , patients undergo autologous PBMC infusion.

Primary Outcome Measures

Name	Time	Method
Frequency of treatment-related grade 3-5 toxicities, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	Within 30 days after infusion of PBMCs	Adverse events will be tabulated by type and grade at each follow-up interval.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	1 year	The level of OS will be tabulated at each follow-up interval, and will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals.
Progression-free survival (PFS)	The duration from SBRT treatment to documented disease progression or death, assessed at 1 year	The level of PFS will be tabulated at each follow-up interval. The percentage of individuals free from disease progression will be computed with exact 95% confidence intervals. PFS will be summarized using Kaplan-Meier curves and medians with 95% confidence intervals.

Trial Locations

Locations (1)

Stanford University Hospitals and Clinics; 🇺🇸 Stanford, California, United States