Phase 2 Study of Nivolumab in Solid Tumors Induced by Prior Radiation Exposure

The purpose of this study is to determine whether Nivolumab is effective in the treatment of radiation-induced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors Induced by Prior Radiation Exposure
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Cancer Center @ Johns Hopkins

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:

• Histologically confirmed metastatic or unresectable solid tumor which standard curative or palliative measures do not exist or are no longer effective. The primary site of the metastatic or unresectable tumor must have arisen within a previously irradiated site and be considered a radiation-induced tumor.
• Pre-treatment tumor specimen available. Patients with no available archived specimen must be willing to undergo a pre-treatment tumor biopsy.
• Measurable disease.
• Progressive disease on study entry.
• Received adjuvant or neoadjuvant chemotherapy and developed recurrent or metastatic disease within 6 months of completing therapy.
• Age >18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status <2.
• Life expectancy of greater than 3 months.
• Adequate organ and marrow function as defined below:
• White Blood Cell >2,000/per microliter
• Absolute neutrophil count >1,500/per microliter
• Platelets >100,000/per microliter
• Hemoglobin ≥9.0 g/dL
• Total bilirubin ≤1.5 times the institutional upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
• Aspartate Aminotransferase(SGOT)/Alanine Aminotransferase (SGPT) <3 X institutional ULN
• Creatinine ≤1.5 X institutional ULN OR
• Creatinine clearance >40 mL/min for patients with creatinine Levels above institutional normal (calculated using the Cockcroft-Gault formula below)
• Female Creatinine Clearance = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
• Male Creatinine Clearance = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
• Women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation and up to 31 weeks after the last dose of nivolumab.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of nivolumab.
• Ability to understand and the willingness to sign a written informed consent document.
• Biopsiable disease at the time of enrollment as biopsies after progression are required for participation.

Exclusion Criteria:

• Any active, known or suspected autoimmune disease.
• Requiring continuous supplemental oxygen.
• Chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or unresolved toxicity due to agents administered more than 2 weeks earlier.
• Uncontrolled brain metastases.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
• Uncontrolled inter-current illness.
• Pregnant or currently breastfeeding.
• Receiving any other anticancer therapy.
• Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA- 4 antibody therapies, any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
• History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating ongoing acute or chronic infection.
• Requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation-Induced Metastatic Sarcoma; a flat dose of Nivolumab 240 mg will be administered intravenously every 2 weeks until disease progression.	Drug: Nivolumab; Other Names: BMS-936558; MDX-1106
Experimental: Radiation-Induced Non-Sarcoma Metastatic Solid Tumors; a flat dose of Nivolumab 240 mg will be administered intravenously every 2 weeks until disease progression.	Drug: Nivolumab; Other Names: BMS-936558; MDX-1106

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Objective Response Rate	Number of participants with response. Response will be assessed at baseline (within 4 weeks prior to starting nivolumab) and then every 8 weeks while on Nivolumab, up to 24 weeks. The best objective response will be assessed at 24 weeks. Response will be defined based on RECIST 1.1 criteria where complete response (CR)= disappearance of all target lesions, partial response (PR) is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Progression-free at 24 Weeks From the Time of Enrollment	Disease status at 24 weeks will be compared to disease status at the time of enrollment, and response coded based on RECIST 1.1 criteria.	24 weeks
Progression-free Survival	Number of participants alive without progression.	Up to 22 months
Duration of Response	The duration of overall response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, accessed up to 3 years.	Up to 22 months
Number of Participants With Treatment-related Adverse Events	Number of participants with treatment-related adverse events as defined by CTCAE 4.0 criteria.	up to 100 days post-intervention
Overall Survival	Overall survival was planned to be measured at 5 years post-intervention as the time from enrollment until death. Instead, due to early termination for low accrual, the number of participants alive at the time of study termination is reported.	Up to 22 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Patrick Forde, MB, BCH, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimate): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Nivolumab; Phase 2 study; radiation-induced solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: J1695; IRB00105682 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

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