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

Pilot Study of Local Tumor Irradiation With Autologous T-Cell Infusion for Metastatic Renal Cell Carcinoma

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics

Participation Criteria

Eligibility Criteria

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

Description

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)

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

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: Treatment (SBRT, autologous PBMC infusion); 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.

Other: laboratory biomarker analysis; Correlative studies; Drug: cyclophosphamide; Given PO; Other Names: Cytoxan; Endoxan; CPM; CTX; Endoxana; Radiation: stereotactic body radiation therapy; Undergo SBRT; Other Names: SBRT; stereotactic radiation therapy; stereotactic radiotherapy; Biological: therapeutic autologous lymphocytes; Undergo autologous PBMC infusion; Other Names: AL; Autologous Lymphocytes; autologous T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Adverse events will be tabulated by type and grade at each follow-up interval.	Within 30 days after infusion of PBMCs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	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.	1 year
Progression-free survival (PFS)	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.	The duration from SBRT treatment to documented disease progression or death, assessed at 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of circulating tumor cells (CTCs)	The correlations of CTCs and changes in signaling as measured by nano-immunoassay (NIA) to clinical response will be assessed. NIA measurements for 20 protein isoforms will be analyzed. Measurements will be analyzed as continuous variables for each sample. The distribution of each isoform will be summarized with medians and interquartile ranges. Quantile plot and box-Cox models will be used to determine whether to transform the data prior to analysis. A protein isoform signature predictive of clinical response will be constructed using the Lasso R glmnet package.	Up to 2 years
Changes in signaling as measured by NIA	The correlations of CTCs and changes in signaling as measured by NIA to clinical response will be assessed. NIA measurements for 20 protein isoforms will be analyzed. Measurements will be analyzed as continuous variables for each sample. The distribution of each isoform will be summarized with medians and interquartile ranges. Quantile plot and box-Cox models will be used to determine whether to transform the data prior to analysis. A protein isoform signature predictive of clinical response will be constructed using the Lasso R glmnet package.	Up to 2 years

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sandy Srinivas, Stanford University Hospitals and Clinics

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 11, 2013
• First Submitted That Met QC Criteria: September 11, 2013
• First Posted (Estimate): September 16, 2013

Study Record Updates

• Last Update Posted (Actual): March 15, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: RENAL0027 (Other Identifier: Stanford University Hospitals and Clinics); P30CA124435 (U.S. NIH Grant/Contract); NCI-2013-01688 (Registry Identifier: CTRP (Clinical Trial Reporting Program))