SBRT (Stereotactic Body Radiation Therapy) in Combination With Nivolumab/Ipilimumab in Renal Cell Carcinoma (RCC) / Kidney Cancer Patients

NCT03065179 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STU 072016-044
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable metastatic lesion that is not being irradiated).

Conditions

Kidney Cancer Metastatic; Kidney Cancer; Kidney Cancer, Stage IV

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-related Adverse Events Grade 3 or Higher as Assessed by CTCAE v4.0

  An adverse event (AE) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  up to 35 months

• Number of Participants Needing Corticosteroids

  up to 35 months

• Objective Response Rate (ORR)

  The ORR is defined as the number of participants with a BOR of CR (Complete response) or PR (Partial response) divided by the number of treated participants. The BOR (Best overall response) is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy including radiotherapy, tumor-directed surgery, or systemic anticancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment

  up to 35 months

Study Arms (1)

Nivolumab/Ipilimumab plus SBRT

EXPERIMENTAL

Induction Dual Immune Checkpoint Inhibition with nivolumab and ipilimumab plus SBRT to 1-2 metastatic sites, followed by nivolumab monotherapy

Drug: Nivolumab/Ipilimumab; Radiation: SBRT

Interventions

Nivolumab/Ipilimumab DRUG

IV immunotherapy

Also known as: Opdivo, Yervoy

Nivolumab/Ipilimumab plus SBRT

SBRT RADIATION

SBRT will be delivered in conjunction with immunotherapy

Also known as: stereotactic radiation

Nivolumab/Ipilimumab plus SBRT

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of RCC with a clear-cell component
• Metastatic (AJCC Stage IV) RCC
• Prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred = or \> 6 months after the last dose of the adjuvant or neoadjuvant therapy
• Any number of prior systemic treatment regimen in the advanced/metastatic setting is allowed (cytokine, anti-angiogenic, mammalian target of rapamycin (mTOR) inhibitor or clinical trial) including previously untreated patients
• Karnofsky Performance Status (KPS) of at least 70%
• Life expectancy of at least 3 months
• At least 2 metastatic sites of which at least 1 must be measurable as per RECIST 1.1
• Archival Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for correlative studies (Note: Fine Needle Aspiration (FNA) and bone metastases samples are not acceptable for submission)
• Patients with favorable, intermediate and poor risk categories will be eligible for the study. Patients must be categorized according to favorable versus intermediate/poor risk status at registration. International Metastatic RCC Database Consortium (IMDC) must be used to determine prognostic factors

You may not qualify if:

• Subjects with previously treated brain or CNS (Central nervous system) metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to study drug administration. Liver metastases will not be included as part of the radiated lesions to be treated.
• Medical History and Concurrent Diseases:
• Prior treatment with an anti-Programmed cell death(PD) -1, anti-PD-L1, anti-PD-L2, anti-CD137(cluster of differentiation), or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein ) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Prior treatment with high dose interleukin (HD IL)-2 is allowed.
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Patients with psoriasis not requiring active, systemic treatment are allowed.
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Uncontrolled adrenal insufficiency
• Requirement for anti-coagulation with Coumadin, low molecular weight heparin and anti-thrombin inhibitors will be accepted if anticoagulation has been stable for at least 4 weeks and no recent history of prior bleeding complications.
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast or low risk Gleason 6 prostate cancer
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection
• Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study drug
• Anti-cancer therapy less than 14 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug
• Presence of any toxicities attributed to prior anti-cancer therapy, other than alopecia, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before administration of study drug
• Physical and Laboratory Test Findings:

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (2)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Nivolumab; Ipilimumab; Radiosurgery

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Hans Hammers
• Organization: UT Southwestern Medical Center

Hans.Hammers@UTSouthwestern.edu

214/645-7445

Study Officials

• Hans Hammers, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Internal Medicine

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 27, 2017
• Study Start: March 1, 2017
• Primary Completion: February 20, 2020
• Study Completion: November 17, 2020
• Last Updated: March 30, 2021
• Results First Posted: March 30, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)