Advanced Non-Small Cell Lung Cancer Progressing After at Least One Prior Therapy For Metastatic Disease

Nivolumab and Ablation For Patients With Advanced Non-Small Cell Lung Cancer Progressing After at Least One Prior Therapy For Metastatic Disease: A Brown University Oncology Research Group Phase II Study

Nivolumab releases the inhibition of the immune system against human cancers. Dramatic and sustained activity has been observed in advanced lung cancer. Ablation may stimulate the immune system by exposing new tumor antigens. Since tumors that express PD-L1 may be more likely to respond to nivolumab, if ablation increases PD-L1 expression (which has not been studied) this treatment may enhance the activity of nivolumab at both the treated site and in other, non-treated, tumors. Ablation is already an FDA approved treatment for cancer. Nivolumab was recently FDA approved for second line treatment of advanced squamous cell NSCLC. The goal of the study will be to determine if the combination of nivolumab and ablation has higher systemic activity than previously reported with nivolumab alone.

Study Overview

• Status: Terminated
• Conditions: NSCLC; Lung Cancer; Metastatic Lung Cancer; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: nivolumab and ablation

Detailed Description

See summary above

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital

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:

• Pathologically or cytologically confirmed NSCLC
• Stage IIIB or stage IV.
• Patient to meet either criterion A or B:

A) Progression after at least 1 line of systemic treatment (IV or oral) for metastatic or locally advanced disease. Must provide documentation systemic treatment was for either locally advanced or metastatic and also scan or assessment to show progression. Radiation does not count as 1 line.

B) Patients progressing within 6 months of completion of neoadjuvant or adjuvant chemotherapy are also eligible without having treatment for metastatic disease (for example patient with stage I disease undergoes resection, receives systemic chemotherapy and then progresses to the liver (now stage IV) within 6 months of chemotherapy). Radiation does not count as 1 line.

• Ablation for advanced lung cancer is being considered by the treating physician for treatment or prevention of symptoms such as pain, bleeding or obstruction- Documentation is required in writing by MD for this criterion.
• At least 1 site of measurable disease that will not be treated with ablation. Sites to send confirmation on which lesion of measurable disease will not be ablated for tracking of response.
• At least 3 weeks since prior chemotherapy and radiation therapy
• No brain metastases except for patients whose metastases have been removed by surgical resection or have had stereotactic radiation or gamma knife with no evidence of active disease on MRI within 28 days of starting treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Life expectancy of at least 12 weeks.
• Required entry laboratory parameters within 14 days of study entry: Granulocytes ≥ 1000/µl; platelet count ≥75,000/µl; absolute lymphocyte count ≥ 500/ µl; Creatinine ≤ 1.5x upper limit normal mg/dl; Bilirubin < 1.5x upper limit normal; AST ≤ 3 x upper limit of normal.
• Age > 18 years
• Men and women of childbearing potential enrolled in this study must agree to use adequate barrier birth control measures during the course of the study and up to 2 months after.
• Written informed consent.

Exclusion Criteria:

• Patients with a history of clinically significant chronic autoimmune disease
• Prior therapy with antibodies that modulate T-cell function defined as anti-CTLA-4, anti-PD-1, and anti-PD-L1
• Conditions currently requiring immunosuppressive medications
• Known history of HIV or hepatitis B or C
• Bleeding diathesis or coagulopathy that in the investigators opinion would prevent ablation from being safely performed.
• Patients with unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• History of organ allograft even if not taking immunosuppressive medications
• Pregnant or breast-feeding.

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 with ablation; 3mg/kg IV over 60 minutes on Day 1 +/- 3 days every 2 weeks until progression for a maximum of 2 years. Either cryoablation or thermal ablation may be performed as per standard institutional policies. As of amendment # 7 submitted to sites November 17, 2017, the dosing for Nivolumab per the FDA guidance was amended to a flat dose of 240mg IV Q2 weeks. As of amendment #8 sent to sites February 22, 2017 the dose of Nivolumab was updated to 3 mg/kg with a maximum dose of 240 mg for patients with weights that would correlate to exceed that dose instead of a flat dose secondary to the standard institutional practice and the FDA guidance .

Drug: nivolumab and ablation; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate of the Combination of Ablation and the PD-1 Inhibitor Nivolumab for Patients With Non-small Cell Lung Cancer (NSCLC) Who Have Progressed Following at Least 1 Prior Chemotherapy Regimen for Metastatic or Locally Advanced Disease.	Assessment of tumor response by scan 12 weeks post the first dose of Nivolumab and approximately every 12 weeks after. Post progression by RECIST a 1 month confirmatory scan will be done and that will be the indicator of Progression.	Up to 5 years.

Collaborators and Investigators

• Sponsor: howard safran
• Collaborators: The Miriam Hospital; Rhode Island Hospital
• Investigators: Principal Investigator: Howard Safran, MD, BrUOG

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: June 8, 2015
• First Submitted That Met QC Criteria: June 9, 2015
• First Posted (Estimate): June 11, 2015

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: BrUOG 317

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.: No