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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Stanford University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01943188
First received: September 11, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Recurrent Renal Cell Cancer
Stage IV Renal Cell Cancer
Radiation: stereotactic body radiation therapy
Drug: cyclophosphamide
Biological: therapeutic autologous lymphocytes
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Local Tumor Irradiation With Autologous T-Cell Infusion for Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Stanford University:

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 [ Time Frame: Within 30 days after infusion of PBMCs ] [ Designated as safety issue: Yes ]
    Adverse events will be tabulated by type and grade at each follow-up interval.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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) [ Time Frame: The duration from SBRT treatment to documented disease progression or death, assessed at 1 year ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Level of circulating tumor cells (CTCs) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Changes in signaling as measured by NIA [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 14
Study Start Date: May 2014
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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) 0-1
  • Absolute neutrophil count (ANC) >= 1.5 X 10^9/L
  • Absolute lymphocyte count (ALC) >= 1.5 X 10^9/L
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100 X 10^9/L
  • Total bilirubin =< 1.5 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X ULN
  • Serum creatinine =< 1.8 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01943188

Locations
United States, California
Stanford University Hospitals and Clinics Recruiting
Stanford, California, United States, 94305
Contact: Denise Haas    650-736-1252    dhaas@stanford.edu   
Principal Investigator: Sandy Srinivas         
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Sandy Srinivas Stanford University Hospitals and Clinics
  More Information

No publications provided

Responsible Party: Stanford University
ClinicalTrials.gov Identifier: NCT01943188     History of Changes
Other Study ID Numbers: RENAL0027, NCI-2013-01688, RENAL0027, P30CA124435
Study First Received: September 11, 2013
Last Updated: June 12, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 01, 2014