Clinical Trials /

Adjuvant Durvalumab for Early Stage NSCLC Patients With ctDNA Minimal Residual Disease

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Description:

In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual blood cancer. If residual cancer using this blood test is detected there may be at higher risk of having the cancer return. The study is going to test whether or not the number of circulating cancer cells detected in the blood can be reduced by administration durvalumab after the standard treatment if you are tested positive for the residual cancer.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Durvalumab for Early Stage NSCLC Patients With ctDNA Minimal Residual Disease
  • Official Title: Adjuvant Durvalumab for Early comStage NSCLC Patients With ctDNA Minimal Residual Disease

Clinical Trial IDs

  • ORG STUDY ID: IRB-54622
  • SECONDARY ID: LUN0115
  • NCT ID: NCT04585477

Conditions

  • Non-small Cell Lung Cancer
  • Non-small Cell Lung Cancer Stage I
  • Non-small Cell Lung Cancer Stage II
  • Non-small Cell Lung Cancer Stage III

Interventions

DrugSynonymsArms
DurvalumabIMFINZI, MEDI4736Cohort 1 minimal residue disease positive(MRD+)

Purpose

In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual blood cancer. If residual cancer using this blood test is detected there may be at higher risk of having the cancer return. The study is going to test whether or not the number of circulating cancer cells detected in the blood can be reduced by administration durvalumab after the standard treatment if you are tested positive for the residual cancer.

Detailed Description

      Primary Objective:

      The primary objective of this study is to measure the change in ctDNA from trial enrollment
      to after 2 cycles of adjuvant durvalumab in subjects with stage I to III NSCLC who had
      positive ctDNA following definitive treatment with surgery or radiation and completion of
      adjuvant standard of care chemotherapy. Secondary Objectives

        1. To compare disease free survival (DFS)

        2. To compare overall survival (OS)

        3. To evaluate the frequency and severity of toxicity

        4. To evaluate the severity of toxicity
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 minimal residue disease positive(MRD+)ExperimentalSubjects with detectable ctDNA (MRD+) will receive up to 12 cycles of durvalumab (1500mg dose by intravenous (by vein) injection every 28 days). ctDNA will be re checked following 2 cycles (8 weeks) of durvalumab and compared to baseline levels. In the absence of progression or toxicity after 2 cycles, subject will continue with durvalumab to complete 1 year of treatment about 10 additional cycles). Subjects will be monitored for secondary endpoints of progression free survival (PFS) and overall survival (OS).
  • Durvalumab
Cohort 2 minimal residue disease negative (MRD-)Active ComparatorSubjects with undetectable ctDNA (MRD) will receive Standard of care and no treatment

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Histologically or cytologically documented NSCLC who present with stage I to III)
                 disease (Version 8 of American Joint Committee on Cancer(AJCC) Staging Manual)
    
              2. Must have received primary treatment with surgery or definitive stereotactic body
                 radiation therapy (SBRT), and not have known disease progression.
    
              3. Aged 18 years or older
    
              4. Life expectancy ³ 12 weeks
    
              5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix B)
    
              6. Absolute neutrophil count > 1.0 x 109/L (1000/mm3)
    
              7. Platelets > 75 x 109/L (100,000/mm3)
    
              8. Hemoglobin ³ 9.0 g/dL (5.59 mmol/L)
    
              9. Measured creatinine clearance > 40 mL/min, by either 24 hour urine collection or the
                 Cockcroft Gault formula
    
                 Males:
    
                 Mass(kg) x (140-Age) / 72 x serum creatinine (mg/dL)
    
                 Females:
    
                 Mass(kg) x (140-Age) x 0.85 / 72 x serum creatinine (mg/dL)
    
             10. Serum bilirubin £ 1.5 x upper limit of normal (ULN). This will not apply to subjects
                 with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is
                 predominantly unconjugated in the absence of evidence of hemolysis or hepatic
                 pathology) who will be allowed in consultation with their physician.
    
             11. Aspartate Aminotransferase (AST) (SGOT)/Alanine Aminotransferase (ALT) (SGPT) £ 2.5 x
                 institutional upper limit of normal (ULN) unless liver metastases are present, in
                 which case it must be £ 5 x ULN
    
             12. AVENIO ctDNA Surveillance Kit Circulating tumor DNA (ctDNA) test result demonstrating
                 either minimal residual disease (MRD) positivity or negativity. Prospective subjects
                 that have indeterminate or no results are NOT ELIGIBLE, but may re test (all other
                 criteria must be met in window).
    
             13. Ability to understand and the willingness to sign the written IRB approved informed
                 consent document.
    
            Exclusion Criteria:
    
            results are NOT ELIGIBLE, but may re test (all other criteria must be met in window).
    
            13.Ability to understand and the willingness to sign the written IRB approved informed
            consent document.
    
            Identify exclusion criteria.
    
              1. Involvement in the planning and/or conduct of the study
    
              2. Previous enrollment or randomization in the present study
    
              3. Participation in another clinical study with an investigational product (ie, non
                 standard of care) during the last 4 weeks prior to the first dose of trial treatment
    
              4. Must not be planning to receive additional immunotherapy apart from this protocol
    
              5. Mixed small cell and non small cell lung cancer histology
    
              6. anaplastic lymphoma kinase (ALK) or ROS1 mutations, or has Epidermal Growth Factor
                 Receptor (EGFR) mutations and PD L1 levels < 1%
    
              7. Known progression of disease following definitive surgery or radiation
    
              8. Developed Grade 2 or higher pneumonitis from prior radiation
    
              9. History of another primary malignancy and currently undergoing active treatment (ie,
                 chemotherapy, hormonal therapy, biologics)
    
             10. Current or prior use of immunosuppressive medication within 14 days before enrollment,
                 with the exceptions of intranasal and inhaled corticosteroids or systemic
                 corticosteroids at physiological doses, which are not to exceed 10 mg/day of
                 prednisone, or an equivalent corticosteroid.
    
             11. Any unresolved toxicity CTCAE > Grade 2 from prior therapy with the exception of
                 alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
    
                   -  Subjects with Grade ³ 2 neuropathy will be evaluated on a case by case basis
                      after consultation with the Protocol Director / Principal Investigator
    
                   -  Subjects with irreversible toxicity that is not reasonably expected to be
                      exacerbated by treatment with durvalumab may be included (ie, hearing loss) only
                      after consultation with the Protocol Director / Principal Investigator.
    
             12. Active or prior documented autoimmune or inflammatory disorders which could limit the
                 subjects ability to receive durvalumab on the study (including inflammatory bowel
                 disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of
                 diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener
                 syndrome [granulomatosis with polyangiitis; Graves' disease; rheumatoid arthritis;
                 hypophysitis; uveitis; etc]). The following may be taken in to considerations as
                 exceptions to this criterion:
    
                   1. Vitiligo or alopecia
    
                   2. Hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
    
                   3. Chronic skin condition not requiring systemic therapy
    
                   4. Those without active disease in the last 5 years may be included, but only after
                      consultation with the study physician
    
                   5. Celiac disease controlled by diet alone
    
             13. History of primary immunodeficiency
    
             14. History of organ transplant requiring therapeutic immunosuppression
    
             15. Active infection including but not limited to:
    
                   -  Tuberculosis
    
                   -  Hepatitis B (HBV )[known positive results for HBV surface antigen (HBsAg) within
                      2 months prior to enrollment]. EXCEPTION: Subjects with a past or resolved HBV
                      infection, defined as the presence of hepatitis B core antibody (anti HBc) and
                      absence of HBsAg are eligible.
    
                   -  Hepatitis C (HCV). EXCEPTION: Subjects positive for HCV antibody are eligible
                      only if polymerase chain reaction is negative for HCV RNA
    
             16. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
                 Subjects, if enrolled, should not receive live vaccine while receiving the
                 investigational product (IP), and through 30 days after the last dose of IP.
    
             17. Uncontrolled intercurrent illness, including but not limited to:
    
                   -  Ongoing or active infection
    
                   -  Symptomatic congestive heart failure
    
                   -  Uncontrolled hypertension
    
                   -  Unstable angina pectoris
    
                   -  Cardiac arrhythmia
    
                   -  Interstitial lung disease
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:Accepts Healthy Volunteers

    Primary Outcome Measures

    Measure:Decrease in ctDNA Level
    Time Frame:8 weeks
    Safety Issue:
    Description:Reduction in minimal residual disease (MRD) will be assessed on the basis of reduction of circulating tumor DNA (ctDNA) in the blood of participants in Cohort 1 MRD+ only. ctDNA is an indicator of MRD. The outcome will be reported as the number of participants who have a ≥ 3-fold drop in ctDNA levels after 2 cycles of durvalumab treatment, a number without dispersion.

    Secondary Outcome Measures

    Measure:Presence or absence of detectable ctDNA
    Time Frame:8 weeks
    Safety Issue:
    Description:Circulating tumor DNA (ctDNA) in the blood is an indicator of minimal residual disease (MRD), a risk factor for future relapse or progression. The outcome will be reported as the number of Cohort 1 MRD+ participants for whom, following 2 cycles of durvalumab, ctDNA was detected, not detected, or unable to be determined, each a number without dispersion. Available data for Cohort 2 MRD- participants will also be reported for the 8-week timepoint.
    Measure:Overall survival (OS)
    Time Frame:12 months
    Safety Issue:
    Description:Overall survival (OS) defined as the duration from study registration until death due to any cause. The outcome will be reported as the number of participants in each cohort known to be alive at 12 months after study registration, a number without dispersion.
    Measure:Disease-free survival (DFS)
    Time Frame:8 weeks
    Safety Issue:
    Description:Disease-free survival (DFS) is defined as the number of participants remaining alive without disease progression (DP), symptomatic deterioration, or death due to any cause. DP is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as follows. Complete Response (CR) = Disappearance of all target lesions Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions Progressive disease (PD) = 20% increase in the sum of the diameters of target lesions (must be > 5 mm), unequivocal progression of non-target lesions, and/or the appearance of one or more new lesion(s) Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome will be reported as the number of participants who meet the criteria for DFS, a number without dispersion.
    Measure:Related Adverse Events
    Time Frame:12 months
    Safety Issue:
    Description:Related adverse events (AEs) are deleterious events determined to be possibly, probably, or definitely-related to durvalumab treatment. The outcome will be reported as the number of related AEs experienced by the participants in Cohort 1 MRD+ only (ie, durvalumab treatment cohort), a number without dispersion.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Stanford University

    Last Updated

    October 6, 2020