Clinical Trials /

Durvalumab Followed by Chemoradiation and Consolidation Durvalumab for Stage III Non-small Cell Lung Cancer

NCT04364048

Description:

Single arm study of induction durvalumab (1500 mg IV) for 1 cycle (every 4 weeks), administered prior to starting concurrent definitive chemoradiation, followed by consolidation durvalumab (1500 mg IV every 4 weeks) for up to 12 cycles. The study will include an initial safety run-in portion. Patients in the safety run-in will be monitored through completion of induction durvalumab, chemoradiation, and 2 cycles of consolidation durvalumab for assessment of safety prior to completion of enrollment.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab Followed by Chemoradiation and Consolidation Durvalumab for Stage III Non-small Cell Lung Cancer
  • Official Title: Induction Durvalumab Followed by Chemoradiation and Consolidation Durvalumab (MEDI4736) for Stage III Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: LUN18-357
  • NCT ID: NCT04364048

Conditions

  • Lung Cancer
  • Non-small Cell Carcinoma

Interventions

DrugSynonymsArms
Induction DurvalumabIMFINZIInduction durvalumab, chemoradiation, consolidation durvalumab
Chemotherapycisplatin, carboplatin, etoposide, pemetrexed, taxaneInduction durvalumab, chemoradiation, consolidation durvalumab
Consolidation durvalumabIMFINZIInduction durvalumab, chemoradiation, consolidation durvalumab

Purpose

Single arm study of induction durvalumab (1500 mg IV) for 1 cycle (every 4 weeks), administered prior to starting concurrent definitive chemoradiation, followed by consolidation durvalumab (1500 mg IV every 4 weeks) for up to 12 cycles. The study will include an initial safety run-in portion. Patients in the safety run-in will be monitored through completion of induction durvalumab, chemoradiation, and 2 cycles of consolidation durvalumab for assessment of safety prior to completion of enrollment.

Trial Arms

NameTypeDescriptionInterventions
Induction durvalumab, chemoradiation, consolidation durvalumabExperimentalInduction durvalumab at 1500 mg intravenously (IV) on Day 1 of a four week cycle for 1 cycle, followed by concurrent definitive chemoradiation, followed by consolidation durvalumab at 1500 mg IV Day 1 of every 4 week cycle for up to 12 cycles.
  • Induction Durvalumab
  • Chemotherapy
  • Consolidation durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent and HIPAA authorization for release of personal health
             information prior to registration. NOTE: HIPAA authorization may be included in the
             informed consent or obtained separately.

          -  Age ≥ 18 years at the time of consent.

          -  ECOG Performance Status of 0 or 1.

          -  Histological or cytological confirmation of stage III non-small cell lung cancer per
             AJCC, 8th edition, eligible for curative-intent concurrent chemoradiation. NOTE:
             subjects are not candidates for surgical resection either due to medical inoperability
             or surgically unresectable disease.

          -  Measurable disease according to RECIST 1.1 criteria.

          -  Plan for treatment with concurrent chemoradiation with a dose of radiation ranging
             from 54-66 Gy:

               -  Planned mean dose delivery to the lung <20 Gy

               -  V20 <35%

          -  No prior therapy for stage III NSCLC.

          -  Demonstrate adequate organ function as defined in the table below. All screening labs
             to be obtained within 14 days prior to registration.

               -  Hemoglobin ≥ 9.0 g/dL

               -  White blood cell (WBC) ≥ 3,000/mm3

               -  Absolute neutrophil count (ANC) ≥ 1,500/mm3

               -  Platelet count ≥ 100,000/mm3

               -  Calculated creatinine clearance ≥ 40 mL/min

               -  Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) ≤ 2.5 x institutional ULN

               -  Alanine aminotransferase (ALT) ≤ 2.5 x institutional ULN

          -  Females of childbearing potential must have a negative serum pregnancy test within 14
             days prior to registration. NOTE: Females are considered of child bearing potential
             unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least
             12 consecutive months.

          -  Females of childbearing potential must be willing to abstain from heterosexual
             activity or to use 2 forms of effective methods of contraception from the time of
             informed consent until 180 days after treatment discontinuation. The two contraception
             methods can be comprised of two barrier methods, or a barrier method plus a hormonal
             method.

          -  Men who are sexually active with WOCBP must use any contraceptive method with a
             failure rate of less than 1% per year. Men receiving study drug and who are sexually
             active with WOCBP will be instructed to adhere to contraception from the time of
             informed consent and for a period of 180 days after treatment discontinuation.

          -  Life expectancy of at least 12 weeks per investigator discretion.

          -  As determined by the enrolling physician or protocol designee, ability of the subject
             to understand and comply with study procedures for the entire length of the study.

        Exclusion Criteria:

          -  Prior therapy for stage III NSCLC

          -  Mixed histology with small cell lung cancer will not be allowed.

          -  Sequential chemoradiation will not be permitted.

          -  Induction and consolidation chemotherapy (separate from concurrent chemoradiation)
             will not be allowed.

          -  Prior exposure to anti-PD-1 or anti-PD-L1 antibodies including durvalumab.

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of durvalumab. The following are exceptions to this criterion:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
                  articular injection)

               -  Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
                  prednisone or its equivalent

               -  Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication)

          -  History of pulmonary fibrosis, interstitial lung disease, or pneumonitis requiring
             steroids.

          -  Active or prior documented autoimmune disease within the last 2 years. Patients with
             vitiligo, stable hypothyroidism, Grave's disease, or psoriasis not requiring systemic
             treatment are not excluded.

          -  Body weight < 30 kg

          -  Active and ongoing steroid use, except for non-systemically absorbed treatments (such
             as inhaled or topical steroid therapy for asthma, COPD, allergic rhinitis).

          -  Active infection requiring systemic therapy.

          -  Uncontrolled current illness that in the opinion of the investigator renders the
             investigational treatment plan unsafe.

          -  Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential who are not willing to employ effective birth control from
             screening to 90 days after the last dose of durvalumab monotherapy.

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
             Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
             30 days after the last dose of IP.

          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of IP. NOTE: Local surgery of isolated lesions for palliative intent is
             acceptable.

          -  Active other malignancy; exceptions include basal cell or squamous cell skin cancer,
             in situ cervical or bladder cancer.

          -  Active infection including tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and TB testing in line with
             local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
             hepatitis C Patients with a past or resolved HBV infection (defined as the presence of
             hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients
             positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction
             is negative for HCV RNA.

          -  Treatment with any investigational drug within 30 days prior to registration.

          -  History of organ transplantation (including allogeneic stem cell transplantation).

          -  Other medical or psychiatric conditions that in the opinion of the site investigator
             would preclude safe participation in this protocol.

        Eligibility Criteria for Consolidation Durvalumab

          -  Patients must have recovered from toxicities associated with prior chemoradiation to
             CTCAE < Grade 2.

          -  Patients must not have progressed following chemoradiation therapy, as measured on
             imaging per RECIST 1.1.

          -  Confirmation of ECOG Performance Status of 0 or 1.

          -  Any grade pneumonitis from prior chemoradiation will not be permitted.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:12 months
Safety Issue:
Description:12-month progression-free survival will be measured using imaging after completion of chemoradiation, prior to C1 consolidation durvalumab (1-42 days after completion of chemoradiation). This will be compared with PACIFIC trial 12-month progression-free survival as historical control.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:12 months
Safety Issue:
Description:ORR will be measured using two timepoints, per RECIST 1.1. "ORR1" will be assessed using baseline imaging in comparison to imaging obtained after completion of induction durvalumab and chemoradiation. "ORR2" will be assessed using imaging after completion of induction durvalumab and chemoradiation in comparison to imaging obtained while receiving, and after completion of, consolidation durvalumab.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rachel Sanborn

Last Updated

July 6, 2020