Combination Radiation and PD-1 Inhibition in Metastatic or Recurrent Renal Cell Carcinoma (RCC)

Combination Radiation and PD-1 Inhibition in Metastatic or Recurrent RCC

There are two primary aims in the study: 1) to determine the tolerability and feasibility of combination hypofractionated radiation therapy and PD-1 inhibition with nivolumab, and 2) to determine the ability of hypofractionated radiation therapy to enhance response rate from PD-1 inhibition versus PD-1 inhibition alone by comparing the observed response rate under the combination therapy with a previously reported response rate under inhibition alone.

Study Overview

• Status: Withdrawn
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: Nivolumab; Radiation: Radiation

Detailed Description

Patients with metastatic or recurrent renal cell cancer who have progressed on standard Tyrosine Kinase Inhibitor (TKI) therapy and who have metastatic or primary tumors suitable for palliative radiation will be eligible for this study. Treatment will consist of nivolumab plus hypofractionated radiation therapy. The primary endpoint will be objective response rate, which will be compared against the historical control of 25% using nivolumab alone as established in the CHECKMATE 025 clinical trial. Patients will continue on nivolumab until disease progression or withdrawal of consent. Follow-up will continue for 2 years.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

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:

1. Histologically confirmed history of renal cell carcinoma (all variants are acceptable)
2. Progression or recurrence after at least one prior tyrosine kinase inhibitor therapy including, but not limited to: sunitinib, pazopanib, axitinib.

3. At least 1 site (primary or metastasis) amenable to hypofractionated radiation therapy and appropriate for radiation therapy as part of standard of care per medical, urologic or radiation oncologist discretion. NOTE: CT / MRI imaging to have been completed no more than 30 days before enrollment on study.

   Potential indications for radiation therapy include (but are not limited to):

   • Painful bone or soft tissue metastasis
   • Symptoms from mass effect caused by tumor
   • Prevention of impending symptoms from tumor
   • Hemoptysis due to tumor
   • Limited oligometastasis
   • Isolated region of progression
4. Patients with prior IL-2 treatment are eligible
5. At least 14 days since any prior therapy
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 3

7. Adequate organ and marrow function as defined below:

   • leukocytes ≥ 2,000/mcL
   • absolute neutrophil count ≥ 1,000/mcL
   • platelets ≥ 100,000/mcL
   • total bilirubin within normal institutional limits
   • AST(SGOT) ≤ 2.5 X institutional upper limit of normal
   • ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
8. Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception. Men of child-bearing potential must not donate sperm while on this study and for 90 days after their last study treatment.

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
2. Men who are trying to father a child.
3. Presence of a condition or abnormality that in the opinion of the study-delegated investigator would compromise the safety of the patient or the quality of the data.

4. Requirement for high dose steroids: dexamethasone > 2 mg per day or equivalent

   • NOTE: Per OPDIVO (Nivolumab) package insert, no formal pharmacokinetic drug-drug interaction studies have been conducted with OPDIVO (Nivolumab) - therefore, no other concomitant medications will exclude potential participants.
5. Life expectancy < 6 months.
6. Other active malignancy (patients with no evidence of disease (NED) or are in remission are eligible).
7. Patient has untreated brain metastases. Patients are eligible after documented stable or improved brain metastases at least 1 month after treatment of brain metastases.
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD-1 Inhibitors used in study.
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
10. Patients with active, known or suspected autoimmune disease (not including type 1 diabetes mellitus, hypothyroidism, skin disorders not requiring systemic treatment or conditions not expected to recur).
11. Patients with interstitial lung disease
12. Patients receiving concurrent other cancer-directed therapy including, but not limited to, Tyrosine Kinase Inhibitor (TKI), Mammalian Target Of Rapamycin (mTOR) inhibition and/or chemotherapy.

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: Nivolumab plus radiation	Drug: Nivolumab; 240 mg per IV infusion over 60 minutes every 14 days (+/- 2 days) until disease progression or participant withdrawal from study; Other Names: OPDIVO; Radiation: Radiation; Radiation to at least 1 site (up to 3) of primary or metastasis, 5 fractions - delivered over 2 weeks, starting 1-3 days post-nivolumab administration. Recommended dose range is 6 Gy-12 Gy per fraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Objective response rate (ORR) defined as the sum of partial response (PR) and complete response (CR). Timeframe will be best response from registration to end of treatment.	Every 3 months up to 2 years or progression

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival (PFS)	12 months
ORR at irradiated sites	Every 3 months up to 2 years or progression
ORR at un-irradiated sites	Every 3 months up to 2 years or progression

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center

Study record dates

Study Major Dates

• Primary Completion (Actual): February 2, 2017

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): March 5, 2018
• Last Update Submitted That Met QC Criteria: March 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: cancer; kidney; metastatic; recurrent; renal cell
• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: IIT2016XSGURadPlusPD1RenalCC