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

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ClinicalTrials.gov Identifier: NCT04093167
Recruitment Status : Recruiting
First Posted : September 17, 2019
Last Update Posted : April 6, 2020
Sponsor:
Collaborators:
Cancer Research Institute, New York City
Personal Genome Diagnostics (PGDx)
Mark Foundation for Cancer Research
Information provided by (Responsible Party):
Canadian Cancer Trials Group

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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Pembrolizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 17, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab
200mg IV every 3 weeks
Drug: Pembrolizumab
200mg IV




Primary Outcome Measures :
  1. Concordance rate between molecular response and radiologic response [ Time Frame: 18 months ]
    Molecular response will be assessed by measuring changes in ctDNA levels in plasma


Secondary Outcome Measures :
  1. Time to molecular response [ Time Frame: 18 months ]
  2. Correlate molecular response to RECIST response based on changes in ctDNA levels [ Time Frame: 18 months ]
  3. Correlate molecular response to progression-free survival based on changes in ctDNA levels [ Time Frame: 18 months ]
  4. Correlate molecular response to overall survival based on changes in ctDNA levels [ Time Frame: 18 months ]
  5. Explore the degree of ctDNA reduction with clinical outcomes assessed by measuring changes in ctDNA levels in plasma [ Time Frame: 18 months ]


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.


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

Inclusion Criteria:

  • Histologically or cytologically confirmed stage IV non-squamous NSCLC (includes M1a, M1b, and M1c stage disease, AJCC 8th edition). Patients with T4NX disease (Stage IIIB) with nodule in ipsilateral lung lobe are eligible if they are not candidates for combined chemotherapy and radiation. Patients with Large Cell Neuroendocrine Carcinoma (LCNEC) are not eligible.
  • Confirmed EGFR and ALK mutation negative disease
  • Patients must have a PD-L1 test result from a certified laboratory indicating PD-L1 expression Tumour Proportion Score (TPS) ≥ 50%.
  • 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 radiation, is allowed as long as a period of 2 weeks has passed since completion.
  • 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 according to the guidance/indications described in the Product Monograph (Canada) or Drug Label (U.S.). 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 confirm access to and 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 brain metastases or leptomeningeal metastases are eligible if these have been treated and follow up brain imaging shows no evidence of progression or if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents).
  • History of primary immunodeficiency or history of allogeneic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 14 days of study drug administration.
  • Active or prior documented autoimmune or inflammatory disorders. Included are inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions considered to be of low risk for recurrence are permitted to enroll.
  • Serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (including corticosteroid administration), or would put the patient at risk. This includes but is not limited to:

    • History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
    • Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis or any infection requiring systemic therapy).
    • Active peptic ulcer disease or gastritis.
    • Active pneumonitis.
  • Concurrent treatment with other anti-cancer therapy or other investigational anti-cancer agents
  • Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (including unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
  • 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.

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): NCT04093167


Contacts
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Contact: Janet Dancey 613-533-6430 jdancey@ctg.queensu.ca

Locations
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United States, Maryland
The Sidney Kimmel Comprehensive Cancer Centre Recruiting
Baltimore, Maryland, United States, 21231
Contact: Valsamo Anagnostou    410-502-3696      
Canada, British Columbia
BCCA - Vancouver Cancer Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Cheryl Ho    604 877-6000 ext 2445      
Canada, Ontario
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Garth Nicholas    613 737-7700 ext 70178      
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Adrian Sacher    416 946-4501 ext 3550      
Sponsors and Collaborators
Canadian Cancer Trials Group
Cancer Research Institute, New York City
Personal Genome Diagnostics (PGDx)
Mark Foundation for Cancer Research
Investigators
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Study Chair: Valsamo Anagnostou Johns Hopkins University
Study Chair: Cheryl Ho BCCA - Vancouver Cancer Centre

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Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT04093167    
Other Study ID Numbers: BR36
CRI-CCTG-002 ( Other Identifier: CRI )
First Posted: September 17, 2019    Key Record Dates
Last Update Posted: April 6, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents