Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung
Primary Purpose
Lung Cancer, Adenocarcinoma of the Lung
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Nivolumab
GM.CD40L Vaccine
Sponsored by
About this trial
This is an interventional treatment trial for Lung Cancer focused on measuring advanced, metastatic, lung disease, adenocarcinoma, non-small cell lung cancer (NSCLC)
Eligibility Criteria
Inclusion Criteria:
- Histologic or cytologic diagnosis of advanced/metastatic adenocarcinoma of the lung
- Eastern Cooperative Oncology Group (ECOG) performance status of 0/1
- Chemotherapy naïve or have completed adjuvant chemotherapy for non-small cell lung cancer (NSCLC) >6 months prior
- Adequate bone marrow, renal and hepatic function
- Must have measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
- Mandatory archival tissue or willingness to undergo a fresh biopsy
- Life expectancy of greater than 6 months
Exclusion Criteria:
- Symptomatic brain metastasis or uncontrolled central nervous system (CNS) metastasis
- Pregnancy or breast feeding
- Serious uncontrolled medical disorder or active infection that would impair the participant's ability to receive study treatment
- Prior use of a PD1 or PDL1 inhibitor
- Concurrent use of other anticancer approved or investigational agents is not allowed
- Autoimmune disorders
- Prior malignancy in past 2 years
- Systemic steroids at doses greater than 10 mg/day of prednisone or the equivalent
- Any other pre-existing immunodeficiency condition (including known HIV infection)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Phase I and Phase II Treatment Arm
Phase II Control Arm
Arm Description
Participants will receive nivolumab and GM.CD40L. Treatment will be administered on an outpatient basis. The nivolumab will be given first followed by the GM.CD40L vaccine for those enrolled on this arm.
Nivolumab treatment without GM.CD40L. Nivolumab will be given every 2 weeks at a dose of 3mg/kg.
Outcomes
Primary Outcome Measures
Phase I: Recommended Phase II Dose
The recommended Phase II dose will be defined as the highest dose level of GMCD40L vaccine in combination with nivolumab that induced dose limiting toxicity (DLT) in fewer than 33% of patients.
Phase II: Objective Response Rate (ORR)
Objective tumor response per treatment arm. ORR: Complete Response (CR) = disappearance of all target lesions + Partial Response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
Secondary Outcome Measures
Phase II: Overall Survival (OS)
OS per treatment arm. Overall survival is defined as the time from randomization until death from any cause.
Phase II: Progression-free Survival (PFS)
PFS per treatment arm. Progressive Disease (PD): = 20% increase in the sum of the longest diameter of target lesions.
Full Information
NCT ID
NCT02466568
First Posted
June 5, 2015
Last Updated
September 6, 2019
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02466568
Brief Title
Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung
Official Title
A Randomized Phase I/II Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Withdrawn
Why Stopped
Funding unavailable
Study Start Date
July 2018 (Anticipated)
Primary Completion Date
July 2019 (Anticipated)
Study Completion Date
July 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to find out what effects (good and bad) a tumor vaccine (GM.CD40L) used in combination with Nivolumab will have on participants and their cancer. Another purpose of the study is to find out the maximum tolerated dose of nivolumab in combination with GM.CD40L vaccine. Investigators also want to find out if the combination of GM.CD40L and nivolumab can boost the immune system of participants like you, and how their immune system reacts, both before and after the treatment.
Detailed Description
This study has two parts and participants may be involved in either Phase I part or Phase II.
Phase I: Investigators plan to enroll participants in cohorts of 6 and monitor side effects over a 21 day period to determine the maximum tolerated dose (MTD) of nivolumab, which will be given in combination with GM.CD40L. This is being done since this study involves a combination of treatments that have not been studied in humans before and to find the best dose for the Phase II part of the study.
Phase II: Investigators plan to compare any clinical benefit in the participants who receive the combination of GM.CD40L vaccine with nivolumab, to participants that receive only nivolumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer, Adenocarcinoma of the Lung
Keywords
advanced, metastatic, lung disease, adenocarcinoma, non-small cell lung cancer (NSCLC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase I and Phase II Treatment Arm
Arm Type
Experimental
Arm Description
Participants will receive nivolumab and GM.CD40L. Treatment will be administered on an outpatient basis. The nivolumab will be given first followed by the GM.CD40L vaccine for those enrolled on this arm.
Arm Title
Phase II Control Arm
Arm Type
Active Comparator
Arm Description
Nivolumab treatment without GM.CD40L. Nivolumab will be given every 2 weeks at a dose of 3mg/kg.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo, Anti-PD-1
Intervention Description
Participants will receive treatment with nivolumab as a 60-minute +/-5 minutes intravenous (IV) infusion on Day 1 and 15 of each 28-day cycle.
Intervention Type
Biological
Intervention Name(s)
GM.CD40L Vaccine
Other Intervention Name(s)
Immunotherapy, Cell Vaccine
Intervention Description
GM.CD40L will be injected intradermally every 2 weeks for 4 injections, then every month for 4 injections, then every 3 months until the patient is off treatment.
Primary Outcome Measure Information:
Title
Phase I: Recommended Phase II Dose
Description
The recommended Phase II dose will be defined as the highest dose level of GMCD40L vaccine in combination with nivolumab that induced dose limiting toxicity (DLT) in fewer than 33% of patients.
Time Frame
Up to 2 months
Title
Phase II: Objective Response Rate (ORR)
Description
Objective tumor response per treatment arm. ORR: Complete Response (CR) = disappearance of all target lesions + Partial Response (PR) = 30% decrease in the sum of the longest diameter of target lesions.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Phase II: Overall Survival (OS)
Description
OS per treatment arm. Overall survival is defined as the time from randomization until death from any cause.
Time Frame
Up to 2 years
Title
Phase II: Progression-free Survival (PFS)
Description
PFS per treatment arm. Progressive Disease (PD): = 20% increase in the sum of the longest diameter of target lesions.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologic or cytologic diagnosis of advanced/metastatic adenocarcinoma of the lung
Eastern Cooperative Oncology Group (ECOG) performance status of 0/1
Chemotherapy naïve or have completed adjuvant chemotherapy for non-small cell lung cancer (NSCLC) >6 months prior
Adequate bone marrow, renal and hepatic function
Must have measurable metastatic disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
Mandatory archival tissue or willingness to undergo a fresh biopsy
Life expectancy of greater than 6 months
Exclusion Criteria:
Symptomatic brain metastasis or uncontrolled central nervous system (CNS) metastasis
Pregnancy or breast feeding
Serious uncontrolled medical disorder or active infection that would impair the participant's ability to receive study treatment
Prior use of a PD1 or PDL1 inhibitor
Concurrent use of other anticancer approved or investigational agents is not allowed
Autoimmune disorders
Prior malignancy in past 2 years
Systemic steroids at doses greater than 10 mg/day of prednisone or the equivalent
Any other pre-existing immunodeficiency condition (including known HIV infection)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jhanelle Gray, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung
We'll reach out to this number within 24 hrs