search
Back to results

Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC

Primary Purpose

Non-Small Cell Lung Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pembrolizumab
Sponsored by
Canadian Cancer Trials Group
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:

  • Histologically or cytologically confirmed metastatic NSCLC. Patients with stage III disease are eligible if they are not candidates for surgical resection or definitive chemoradiation. Patients with Large Cell Neuroendocrine Carcinoma (LCNEC) are not eligible.
  • Confirmed EGFR and ALK mutation-negative disease. Testing for EGFR and ALK is not required for patients with squamous histology.
  • Patients must have a PD-L1 test result from a certified laboratory indicating PD-L1 expression Tumour Proportion Score (TPS) ≥ 1%.
  • No prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for locally advanced Stage III disease is allowed if at least 6 months have elapsed since the prior therapy and enrollment. Local therapy, e.g. palliative extra-cranial radiation, is allowed as long as a period of 2 weeks has passed since completion as ctDNA levels may be altered by radiotherapy. There is no requirement for delay for patients who have received brain radiation.
  • Patients must have recovered to ≤ grade 1 from all reversible toxicity related to prior systemic or radiation therapy.
  • Previous major surgery is permitted provided that surgery occurred at least 28 days prior to patient enrollment and that wound healing has occurred.
  • Eligible to receive treatment with pembrolizumab. Reimbursement of pembrolizumab may not be uniform across all sites. In the event that the site/investigator is unable to provide access to the drug, the patient will not be eligible for this trial.
  • Must be ≥ 18 years of age.
  • ECOG performance status 0 or 1.
  • Clinically and/or radiologically documented disease with at least one lesion measurable as defined by RECIST 1.1.
  • Imaging investigations including CT of the chest, abdomen and pelvis and MRI of the brain (if known brain metastases) or other scans as necessary to document all sites of disease must be done within 28 days prior to enrollment.
  • Adequate hematology and organ function as defined below (must be done within 14 days prior to enrollment).

    • White Blood Cells ≥ 2.0 x 10^9/L (2000/μL)
    • Absolute neutrophils ≥ 1.5 x 10^9/L (1500/μL)
    • Platelets ≥ 100 x 10^9/L (100 x 10^3/μL)
    • Bilirubin ≤ 1.5 x ULN (upper limit of normal)*
    • AST and/or ALT ≤ 3 x ULN, < 5 x ULN for patients with liver metastases
    • Serum creatinine or Creatinine clearance ≤ 1.5 x ULN OR ≥ 40 mL/min
  • Patients must consent to provision of, and investigator must agree to submit, a representative archival formalin-fixed paraffin block of tumour tissue for correlative analyses when tumour tissue is available.
  • Patients must consent to collection of liquid biopsy (blood) samples for ctDNA analysis by CLIA central laboratory and for correlative analysis by a research central laboratory.
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment to the trial to document their willingness to participate.
  • Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, collection of blood samples, response assessments and follow-up. Patients must agree to return to their primary care facility for response assessments as well as any adverse events which may occur through the course of the trial.
  • In accordance with CCTG policy, protocol treatment with pembrolizumab is to begin within 2 working days of patient enrollment.
  • Women/men of childbearing potential must have agreed to use a highly effective contraceptive method. Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation.

Exclusion Criteria:

  • Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients with symptomatic central nervous system (CNS) metastases and/or CNS metastases requiring immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents). Patients with known central nervous system metastases who are asymptomatic and on a stable dose of corticosteroids ≤ 10 mg/day prednisone equivalents prior to enrollment are eligible.
  • Patients who are not suitable candidates for treatment with pembrolizumab according to the current guidance/indications described in the Product Monograph (Canada) or Drug Label (U.S.) including but not limited to patients with active infection, autoimmune disease, conditions that require systemic immunosuppressive therapy (such as transplant patients) and patients with a history of severe immune-mediated adverse reactions, or known hypersensitivity to pembrolizumab or its components. Patients with pre-existing conditions such as colitis, hepatic impairment, respiratory or endocrine disorders (such as hypo or hyperthyroidism or diabetes mellitus), can be considered for enrollment to this study provided pembrolizumab is administered with caution and patients are closely monitored
  • History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
  • Concurrent treatment with other anti-cancer therapy or other investigational anti-cancer agents
  • Pregnant or lactating women.
  • Men who are sexually active with women of childbearing potential and women of childbearing potential must agree to use adequate contraception.

Sites / Locations

  • The Sidney Kimmel Comprehensive Cancer Centre
  • BCCA - Vancouver Cancer Centre
  • Juravinski Cancer Centre at Hamilton Health Sciences
  • Kingston Health Sciences Centre
  • Ottawa Hospital Research Institute
  • University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab

Arm Description

200mg (or 2mg/kg) IV every 3 weeks for cycles 1-3 then as per standard of care for patients with PD-L1+ EGFR/ALK-NSCLC

Outcomes

Primary Outcome Measures

Concordance rate between molecular response and radiologic response
Molecular response will be assessed by measuring changes in ctDNA levels in plasma

Secondary Outcome Measures

Time to molecular response
Correlate molecular response to RECIST response based on changes in ctDNA levels
Correlate molecular response to progression-free survival based on changes in ctDNA levels
Correlate molecular response to overall survival based on changes in ctDNA levels
Explore the degree of ctDNA reduction with clinical outcomes assessed by measuring changes in ctDNA levels in plasma

Full Information

First Posted
September 12, 2019
Last Updated
August 3, 2023
Sponsor
Canadian Cancer Trials Group
Collaborators
Cancer Research Institute, New York City, Personal Genome Diagnostics (PGDx), Mark Foundation for Cancer Research
search

1. Study Identification

Unique Protocol Identification Number
NCT04093167
Brief Title
Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC
Official Title
A Biomarker-Directed, Open Label, Multi-Centre Phase II Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With Non-Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 26, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
July 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Canadian Cancer Trials Group
Collaborators
Cancer Research Institute, New York City, Personal Genome Diagnostics (PGDx), Mark Foundation for Cancer Research

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
The purpose of stage 1 of the study is to find out if blood tests can be used to see how the cancer is responding to treatment with pembrolizumab.
Detailed Description
The standard or usual treatment for this disease is pembrolizumab given by needle every three weeks. This study will be done in two stages. The purpose of stage 1 of the study is to find out if we can use blood tests to see how the cancer is responding to treatment with pembrolizumab. A second stage of the study will take place once stage 1 is completed. In stage 2 blood tests will be used to help determine if patients whose cancer does not seem to be getting better on treatment with pembrolizumab, would do better on a different treatment.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Pembrolizumab
Arm Type
Experimental
Arm Description
200mg (or 2mg/kg) IV every 3 weeks for cycles 1-3 then as per standard of care for patients with PD-L1+ EGFR/ALK-NSCLC
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
200mg IV 2 mg/kg IV 400 mg IV 4 mg/kg IV
Primary Outcome Measure Information:
Title
Concordance rate between molecular response and radiologic response
Description
Molecular response will be assessed by measuring changes in ctDNA levels in plasma
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Time to molecular response
Time Frame
18 months
Title
Correlate molecular response to RECIST response based on changes in ctDNA levels
Time Frame
18 months
Title
Correlate molecular response to progression-free survival based on changes in ctDNA levels
Time Frame
18 months
Title
Correlate molecular response to overall survival based on changes in ctDNA levels
Time Frame
18 months
Title
Explore the degree of ctDNA reduction with clinical outcomes assessed by measuring changes in ctDNA levels in plasma
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed metastatic NSCLC. Patients with stage III disease are eligible if they are not candidates for surgical resection or definitive chemoradiation. Patients with Large Cell Neuroendocrine Carcinoma (LCNEC) are not eligible. Confirmed EGFR and ALK mutation-negative disease. Testing for EGFR and ALK is not required for patients with squamous histology. Patients must have a PD-L1 test result from a certified laboratory indicating PD-L1 expression Tumour Proportion Score (TPS) ≥ 1%. No prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC. Chemotherapy for non-metastatic disease (e.g. adjuvant therapy) or immunotherapy for locally advanced Stage III disease is allowed if at least 6 months have elapsed since the prior therapy and enrollment. Local therapy, e.g. palliative extra-cranial radiation, is allowed as long as a period of 2 weeks has passed since completion as ctDNA levels may be altered by radiotherapy. There is no requirement for delay for patients who have received brain radiation. Patients must have recovered to ≤ grade 1 from all reversible toxicity related to prior systemic or radiation therapy. Previous major surgery is permitted provided that surgery occurred at least 28 days prior to patient enrollment and that wound healing has occurred. Eligible to receive treatment with pembrolizumab. Reimbursement of pembrolizumab may not be uniform across all sites. In the event that the site/investigator is unable to provide access to the drug, the patient will not be eligible for this trial. Must be ≥ 18 years of age. ECOG performance status 0 or 1. Clinically and/or radiologically documented disease with at least one lesion measurable as defined by RECIST 1.1. Imaging investigations including CT of the chest, abdomen and pelvis and MRI of the brain (if known brain metastases) or other scans as necessary to document all sites of disease must be done within 28 days prior to enrollment. Adequate hematology and organ function as defined below (must be done within 14 days prior to enrollment). White Blood Cells ≥ 2.0 x 10^9/L (2000/μL) Absolute neutrophils ≥ 1.5 x 10^9/L (1500/μL) Platelets ≥ 100 x 10^9/L (100 x 10^3/μL) Bilirubin ≤ 1.5 x ULN (upper limit of normal)* AST and/or ALT ≤ 3 x ULN, < 5 x ULN for patients with liver metastases Serum creatinine or Creatinine clearance ≤ 1.5 x ULN OR ≥ 40 mL/min Patients must consent to provision of, and investigator must agree to submit, a representative archival formalin-fixed paraffin block of tumour tissue for correlative analyses when tumour tissue is available. Patients must consent to collection of liquid biopsy (blood) samples for ctDNA analysis by CLIA central laboratory and for correlative analysis by a research central laboratory. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment to the trial to document their willingness to participate. Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, collection of blood samples, response assessments and follow-up. Patients must agree to return to their primary care facility for response assessments as well as any adverse events which may occur through the course of the trial. In accordance with CCTG policy, protocol treatment with pembrolizumab is to begin within 2 working days of patient enrollment. Women/men of childbearing potential must have agreed to use a highly effective contraceptive method. Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation. Exclusion Criteria: Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients with symptomatic central nervous system (CNS) metastases and/or CNS metastases requiring immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents). Patients with known central nervous system metastases who are asymptomatic and on a stable dose of corticosteroids ≤ 10 mg/day prednisone equivalents prior to enrollment are eligible. Patients who are not suitable candidates for treatment with pembrolizumab according to the current guidance/indications described in the Product Monograph (Canada) or Drug Label (U.S.) including but not limited to patients with active infection, autoimmune disease, conditions that require systemic immunosuppressive therapy (such as transplant patients) and patients with a history of severe immune-mediated adverse reactions, or known hypersensitivity to pembrolizumab or its components. Patients with pre-existing conditions such as colitis, hepatic impairment, respiratory or endocrine disorders (such as hypo or hyperthyroidism or diabetes mellitus), can be considered for enrollment to this study provided pembrolizumab is administered with caution and patients are closely monitored History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements. Concurrent treatment with other anti-cancer therapy or other investigational anti-cancer agents Pregnant or lactating women. Men who are sexually active with women of childbearing potential and women of childbearing potential must agree to use adequate contraception.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Valsamo Anagnostou
Organizational Affiliation
Johns Hopkins University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Cheryl Ho
Organizational Affiliation
BCCA - Vancouver Cancer Centre
Official's Role
Study Chair
Facility Information:
Facility Name
The Sidney Kimmel Comprehensive Cancer Centre
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
BCCA - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Juravinski Cancer Centre at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
Kingston Health Sciences Centre
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of Molecular Response Adaptive Immuno-Chemotherapy in Patients With NSCLC

We'll reach out to this number within 24 hrs