Repositioning Immunotherapy in VetArans With Lung Cancer (RIVAL)

Repositioning Immunotherapy in Veterans With Lung Cancer

This study is a multicenter Phase II single arm trial to assess the safety and efficacy of chemotherapy and immunotherapy followed by radiotherapy in patients with unresectable Stage III NSCLC.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael D Green; Phone Number: (734) 845-3914; Email: Michael.Green4@va.gov
• Study Contact Backup: Name: Nithya Ramnath, MD; Email: nithya.ramnath@va.gov

Study Locations

• United States
  • California
    • West Los Angeles, California, United States, 90073-1003
      • Not yet recruiting
      • VA Greater Los Angeles Healthcare System, West Los Angeles, CA
      • Contact: Daniel Shin, MD; Phone Number: 310-478-3711; Email: Daniel.Shin@va.gov
      • Contact: Michelle Treadwell; Phone Number: 45003 3104783711; Email: Michelle.Treadwell@va.gov
  • Connecticut
    • West Haven, Connecticut, United States, 06516-2770
      • Recruiting
      • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
      • Contact: Michal Rose, MD; Phone Number: 2832 203-932-5711; Email: Michal.Rose@va.gov
      • Contact: Alicia Roy; Phone Number: 3006 2039325711; Email: Alicia.Roy@va.gov
  • Michigan
    • Ann Arbor, Michigan, United States, 48105-2303
      • Recruiting
      • VA Ann Arbor Healthcare System, Ann Arbor, MI
      • Contact: Brittany M Pannecouk, BS; Phone Number: 734-845-3966; Email: brittany.pannecouk@va.gov
      • Principal Investigator: Nithya Ramnath, MD
      • Contact: Laura A Randolph, BA; Phone Number: (734) 845-5091; Email: Laura.Randolph@va.gov
      • Principal Investigator: Michael D Green
  • Nebraska
    • Omaha, Nebraska, United States, 68105-1850
      • Not yet recruiting
      • Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
      • Contact: Apar Kishor P Ganti, MD; Phone Number: 3846 402-346-8800; Email: Aparkishor.Ganti@va.gov
      • Contact: Anna Kellogg; Phone Number: 4029954143; Email: Anna.Kellogg@va.gov
  • North Carolina
    • Durham, North Carolina, United States, 27705-3875
      • Not yet recruiting
      • Durham VA Medical Center, Durham, NC
      • Contact: Michael Kelley, MD; Phone Number: 172199 919-286-0411; Email: michael.kelley6@va.gov
      • Contact: Maya Robinson; Phone Number: 9192866926; Email: Maya.Robinson@va.gov
  • Ohio
    • Cleveland, Ohio, United States, 44106-1702
      • Not yet recruiting
      • Louis Stokes VA Medical Center, Cleveland, OH
      • Contact: Charles Nock, MD; Phone Number: 64825 216-791-3800; Email: Charles.Nock@va.gov
      • Contact: Margaret Titkin; Phone Number: 36241 2167913800; Email: MargaretTiktin@va.gov
  • Virginia
    • Richmond, Virginia, United States, 23249-0001
      • Not yet recruiting
      • Hunter Holmes McGuire VA Medical Center, Richmond, VA
      • Contact: Bhaumik Patel, MD; Phone Number: 804-675-5446; Email: Bhaumik.Patel@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be more than 18 years of age.
• Patient must have a performance status of 0-1 (ECOG Performance Scale).
• Patient must be a candidate for concurrent chemoradiation.
• Unresectable Stage III NSCLC as assessed by investigator or multidisciplinary tumor board assessment
• PD-L1 tumor expression greater than or equal to 1%
• Presence of measurable disease according to RECIST v1.1
• Adequate organ function
• Available tissue (archival FFPE preferred) with adequate tumor content ( 20% tumor cellularity).

Exclusion Criteria:

• Active autoimmune disease that has requires immunosuppressive therapy in the previous year.
• Uncontrolled primary or acquired immunodeficiency (including HIV)
• Baseline corticosteroid usage (>10 mg prednisone or equivalent daily) aside from supportive medication use.
• Tumor with known EGFR, ALK, ROS1, MET or RET mutations/fusions.
• Presence of significant comorbidities precluding participation in a clinical study as determined by investigator.
• Prior thoracic radiotherapy or prior systemic treatment for stage IIIB/IV NSCLC
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Has known active Hepatitis B or Hepatitis C.
• Has received a live vaccine within 30 days of enrollment.
• Known diagnosis of Interstitial Lung Disease
• Inability to provide informed consent.

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: Chemoimmunotherapy followed by radiotherapy; Nivolumab (Opdivo) + plus platinum-doublet chemotherapy followed by radiotherapy	Drug: Nivolumab; Carboplatin, paclitaxel, and nivolumab for three cycles (for squamous cell lung cancer) or Carboplatin, pemetrexed, and nivolumab for three cycles (for lung adenocarcinoma) Followed by radiotherapy (60 Gy in 30 fractions) Followed by adjuvant nivolumab (six cycles); Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Defined as the time from start of treatment to radiographic/clinical progression (per irRECIST1.1), or death from any cause, whichever occurs first.	Approximately two years after enrollment
Treatment Tolerance	Proportion of patients able to complete prescribed treatment course (all planned cycles of systemic therapy and all fractions of radiotherapy).	Approximately three years after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Frequency of adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria 5.0 classified by body system, grade, and attribution.	Approximately two years after enrollment
Best overall response rate (BOR)	Defined as the proportion of participants who achieve a confirmed either a best response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by central review.	Approximately two years after enrollment
Overall survival	Defined as the time from start of treatment to the date of death from any cause..	Approximately two years after enrollment

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Nithya Ramnath, MD, VA Ann Arbor Healthcare System, Ann Arbor, MI; Principal Investigator: Michael D Green, VA Ann Arbor Healthcare System, Ann Arbor, MI

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: February 16, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: SPLP-002-23F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes