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

Primary Purpose

Non-small Cell Lung Cancer, Lung Cancer, Metastatic Lung Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
nivolumab and ablation
Sponsored by
howard safran
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Rhode Island Hospital
  • The Miriam Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nivolumab with ablation

Arm Description

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 .

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
June 8, 2015
Last Updated
February 13, 2020
Sponsor
howard safran
Collaborators
Rhode Island Hospital, The Miriam Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02469701
Brief Title
Advanced Non-Small Cell Lung Cancer Progressing After at Least One Prior Therapy For Metastatic Disease
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 Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Why Stopped
Lack of accrual
Study Start Date
February 2016 (undefined)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
howard safran
Collaborators
Rhode Island Hospital, The Miriam Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
See summary above

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer, Lung Cancer, Metastatic Lung Cancer, NSCLC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nivolumab with ablation
Arm Type
Experimental
Arm Description
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 .
Intervention Type
Drug
Intervention Name(s)
nivolumab and ablation
Other Intervention Name(s)
Opdivo
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
Up to 5 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Howard Safran, MD
Organizational Affiliation
BrUOG
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
The Miriam Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States

12. IPD Sharing Statement

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

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