Clinical Trials /

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

NCT04093167

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: BR36
  • SECONDARY ID: CRI-CCTG-002
  • NCT ID: NCT04093167

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimental200mg IV every 3 weeks
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Concordance rate between molecular response and radiologic response
Time Frame:18 months
Safety Issue:
Description:Molecular response will be assessed by measuring changes in ctDNA levels in plasma

Secondary Outcome Measures

Measure:Time to molecular response
Time Frame:18 months
Safety Issue:
Description:
Measure:Correlate molecular response to RECIST response based on changes in ctDNA levels
Time Frame:18 months
Safety Issue:
Description:
Measure:Correlate molecular response to progression-free survival based on changes in ctDNA levels
Time Frame:18 months
Safety Issue:
Description:
Measure:Correlate molecular response to overall survival based on changes in ctDNA levels
Time Frame:18 months
Safety Issue:
Description:
Measure:Explore the degree of ctDNA reduction with clinical outcomes assessed by measuring changes in ctDNA levels in plasma
Time Frame:18 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Canadian Cancer Trials Group

Last Updated

April 2, 2020