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

Primary Purpose

Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

stereotactic body radiation therapy

cyclophosphamide

therapeutic autologous lymphocytes

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University Hospitals and Clinics

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (SBRT, autologous PBMC infusion)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT01943188

First Posted

September 11, 2013

Last Updated

March 13, 2017

Sponsor

Stanford University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01943188

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Terminated

Study Start Date

May 2014 (undefined)

Primary Completion Date

March 2016 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (SBRT, autologous PBMC infusion)

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

stereotactic body radiation therapy

Other Intervention Name(s)

SBRT, stereotactic radiation therapy, stereotactic radiotherapy

Intervention Description

Undergo SBRT

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Other Intervention Name(s)

CPM, CTX, Cytoxan, Endoxan, Endoxana

Intervention Description

Given PO

Intervention Type

Biological

Intervention Name(s)

therapeutic autologous lymphocytes

Other Intervention Name(s)

AL, Autologous Lymphocytes, autologous T cells

Intervention Description

Undergo autologous PBMC infusion

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

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

Description

Adverse events will be tabulated by type and grade at each follow-up interval.

Time Frame

Within 30 days after infusion of PBMCs

Secondary Outcome Measure Information:

Title

Overall survival (OS)

Description

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.

Time Frame

1 year

Title

Progression-free survival (PFS)

Description

Time Frame

The duration from SBRT treatment to documented disease progression or death, assessed at 1 year

Other Pre-specified Outcome Measures:

Title

Level of circulating tumor cells (CTCs)

Description

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.

Time Frame

Up to 2 years

Title

Changes in signaling as measured by NIA

Description

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.

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sandy Srinivas

Organizational Affiliation

Stanford University Hospitals and Clinics

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University Hospitals and Clinics

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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