Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02469701
Recruitment Status : Terminated (Lack of accrual)
First Posted : June 11, 2015
Results First Posted : May 7, 2018
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
Rhode Island Hospital
The Miriam Hospital
Information provided by (Responsible Party):
howard safran, Brown University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Lung Cancer Metastatic Lung Cancer NSCLC Drug: nivolumab and ablation Phase 2

Detailed Description:
See summary above

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : February 2016
Actual Primary Completion Date : July 2017
Actual Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Nivolumab

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 Name: Opdivo




Primary Outcome Measures :
  1. 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. [ Time Frame: Up to 5 years. ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02469701


Locations
Layout table for location information
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
The Miriam Hospital
Providence, Rhode Island, United States, 02906
Sponsors and Collaborators
howard safran
Rhode Island Hospital
The Miriam Hospital
Investigators
Layout table for investigator information
Principal Investigator: Howard Safran, MD BrUOG
  Study Documents (Full-Text)

Documents provided by howard safran, Brown University:
Study Protocol  [PDF] May 22, 2017
Statistical Analysis Plan  [PDF] May 22, 2017

Layout table for additonal information
Responsible Party: howard safran, Prinicipal Investigator, Brown University
ClinicalTrials.gov Identifier: NCT02469701    
Other Study ID Numbers: BrUOG 317
First Posted: June 11, 2015    Key Record Dates
Results First Posted: May 7, 2018
Last Update Posted: February 17, 2020
Last Verified: February 2020

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action