Clinical Trials /

Chemoradiation Followed by Durvalumab in Poor Risk and/or Elderly Patients With Stage III NSCLC

NCT04441138

Description:

Elderly (age 70 years or older) or >18 years old AND poor risk (ECOG 2) newly diagnosed stage IIIA-C (AJCC 8th edition) inoperable non-small cell lung cancer (NSCLC) patients are eligible to participate in this phase II open label study of concurrent, split course chemoradiation followed by Durvalumab (MEDI4736).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Chemoradiation Followed by Durvalumab in Poor Risk and/or Elderly Patients With Stage III NSCLC
  • Official Title: Phase II Trial of Concurrent, Split Course Chemoradiation Followed by Durvalumab (MEDI4736) in Poor Risk and/or Elderly Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: ESR 18-14205
  • NCT ID: NCT04441138

Conditions

  • Stage III Non-small-cell Lung Cancer

Interventions

DrugSynonymsArms
DurvalumabMEDI4736, imfinziConcurrent, Split Course Chemoradiation Followed by Durvalumab

Purpose

Elderly (age 70 years or older) or >18 years old AND poor risk (ECOG 2) newly diagnosed stage IIIA-C (AJCC 8th edition) inoperable non-small cell lung cancer (NSCLC) patients are eligible to participate in this phase II open label study of concurrent, split course chemoradiation followed by Durvalumab (MEDI4736).

Detailed Description

      The rationale for the study is to identify another cohort of stage III NSCLC for whom
      adjuvant Durvalumab can be safely given, expanding its utilization and benefits. With a
      unique, extremely well-tolerated 4-phase split course CRT regimen preceding the
      administration of Durvalumab, we expect to be able to offer adjuvant Durvalumab to a
      significant proportion of patients on study.

      Patients who have completed four cycles of chemoradiation (Radiation is 60 Gy in 30 fractions
      administered over 12 weeks with 1-1.5 week breaks between cycles; Chemotherapy is once every
      3 weeks for up to 4 cycles) will go on to receive durvalumab (MEDI4736) monotherapy as 1500mg
      durvalumab (MEDI4736) via IV infusion Q4W for up to a maximum of 12 months (up to 13
      doses/cycles) with the last administration on week 48 until confirmed disease progression
      unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation
      criterion is met.

      Primary objectives are:

        1. To determine the percentage of poor risk and/or elderly unresectable stage III NSCLC
           patients who complete split course chemoradiation

        2. To determine the safety and tolerability of durvalumab (MEDI4736) after completion of
           chemoradiation in this group of patients.

      Secondary Objectives are:

        1. To determine the 1-year overall survival rate

        2. To determine the 1-year progression-free survival rate

        3. To determine the 1-year loco-regional progression-free survival rate

        4. To determine rate of grade 3 and 4 toxicities with this regimen in the selected patient
           population
    

Trial Arms

NameTypeDescriptionInterventions
Concurrent, Split Course Chemoradiation Followed by DurvalumabExperimentalConcurrent, Split Course Chemoradiation Followed by Durvalumab (MEDI4736) in Poor Risk and/or Elderly Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          1. Participants must have histologically or cytologically confirmed stage IIIA-C (AJCC
             8th edition) non-small cell lung cancer, that will be treated with curative intent.

          2. Participants must have been deemed medically inoperable by multidisciplinary
             team/tumor board

          3. Participants must have been staged with a PET/CT within 30 days of enrollment

          4. Patients must have undergone an MRI Brain w/IV contrast, or CT brain if MRI not
             feasible, confirming no evidence of brain metastases, within 30 days of enrollment.

          5. Participants must be elderly (age 70 years or older and PS 0-1) or >18 years old AND
             poor risk (ECOG 2)

          6. Participants ideally have endobronchial ultrasound biopsy (EBUS) or mediastinoscopy to
             confirm nodal status, but can be deferred if PET/CT imaging characteristics are highly
             suggestive of nodal metastases

          7. Participants should have a life expectancy of >6 months

          8. Participants must have normal organ and marrow function: Leukocytes >3000/mcL; ANC
             >1500/mcL; PLT>100000/mcL; Hemoglobin ≥9.0 g/dL

          9. Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)

         10. AST/ALT <2.5 x institutional upper limit of normal

         11. Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by
             the Cockcroft-Gault formula

             Males:

             Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)

             Females:

             Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine
             (mg/dL)

         12. Patients must be capable of giving signed informed consent which includes compliance
             with the requirements and restrictions listed in the informed consent form (ICF) and
             in this protocol. Written informed consent and any locally required authorization (eg,
             Health Insurance Portability and Accountability Act in the US, European Union [EU]
             Data Privacy Directive in the EU) obtained from the patient/legal representative prior
             to performing any protocol-related procedures, including screening evaluations. If
             study includes Japan add (For patients aged <20 years and enrolling in Japan, a
             written informed consent should be obtained from the patient and his or her legally
             acceptable representative.)

         13. Body weight >30kg

         14. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

             Women <50 years of age would be considered post-menopausal if they have been
             amenorrheic for 12 months or more following cessation of exogenous hormonal treatments
             and if they have luteinizing hormone and follicle-stimulating hormone levels in the
             post-menopausal range for the institution or underwent surgical sterilization
             (bilateral oophorectomy or hysterectomy).

             Women ≥50 years of age would be considered post-menopausal if they have been
             amenorrheic for 12 months or more following cessation of all exogenous hormonal
             treatments, had radiation-induced menopause with last menses >1 year ago, had
             chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical
             sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

         15. Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up.

        Exclusion Criteria:

          1. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to carboplatin, pemetrexed (for patients with adenocarcinoma), etoposide
             (for patients with squamous cell carcinoma), or immunotherapy

          2. Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or
             psychiatric/social situations that would limit compliance with study requirements.

          3. Pregnant women

          4. HIV positive patients

          5. Participation in another clinical study with an investigational product during the
             last 6 months

          6. Concurrent enrolment in another clinical study, unless it is an observational
             (non-interventional) clinical study or during the follow-up period of an
             interventional study

          7. Receipt of the last dose of anticancer therapy (CRT) ≤7 days prior to the first dose
             of study drug. If sufficient wash-out time has not occurred due to the schedule or PK
             properties of an agent, a longer wash-out period will be required, as agreed by
             AstraZeneca/MedImmune and the investigator

          8. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
             criteria

               1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after
                  consultation with the Study Physician.

               2. Patients with irreversible toxicity not reasonably expected to be exacerbated by
                  treatment with durvalumab may be included only after consultation with the Study
                  Physician.

          9. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
             Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
             replacement therapy) is acceptable.

         10. 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.

         11. History of allogenic organ transplantation.

         12. Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., 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 are exceptions to this
             criterion:

               1. Patients with vitiligo or alopecia

               2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement

               3. Any chronic skin condition that does not require systemic therapy

               4. Patients without active disease in the last 5 years may be included but only
                  after consultation with the study physician

               5. Patients with celiac disease controlled by diet alone

         13. 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, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirement, substantially increase
             risk of incurring AEs or compromise the ability of the patient to give written
             informed consent

         14. History of another primary malignancy except for

               1. Malignancy treated with curative intent and with no known active disease ≥5 years
                  before the first dose of IP and of low potential risk for recurrence

               2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               3. Adequately treated carcinoma in situ without evidence of disease

         15. History of leptomeningeal carcinomatosis

         16. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
             calculated from 3 ECGs (within 15 minutes at 5 minutes apart) <<for durvalumab
             monotherapy.

         17. History of active primary immunodeficiency

         18. 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, or human immunodeficiency virus (positive HIV 1/2 antibodies). 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.

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

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

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

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

         20. 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.

         21. 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.

         22. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients.

         23. Prior randomisation or treatment in a previous durvalumab clinical study regardless of
             treatment arm assignment.

         24. Patients who have received prior anti-PD-1, anti PD-L1, including durvalumab or anti
             CTLA-4:

               1. Must not have experienced a toxicity that led to permanent discontinuation of
                  prior immunotherapy.

               2. All AEs while receiving prior immunotherapy must have completely resolved or
                  resolved to baseline prior to screening for this study.

               3. Must not have experienced a ≥Grade 3 immune related AE or an immune related
                  neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE:
                  Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably
                  maintained on appropriate replacement therapy and are asymptomatic.

               4. Must not have required the use of additional immunosuppression other than
                  corticosteroids for the management of an AE, not have experienced recurrence of
                  an AE if re-challenged, and not currently require maintenance doses of > 10 mg
                  prednisone or equivalent per day.

         25. Judgment by the investigator that the patient is unsuitable to participate in the
             study and the patient is unlikely to comply with study procedures, restrictions and
             requirements.

        Procedures for withdrawal of incorrectly enrolled patients are presented in Section 4.3
        Withdrawal of patients from study treatment and/or study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of split course chemoradiation completion
Time Frame:3 months
Safety Issue:
Description:To determine the percentage of poor risk and/or elderly unresectable stage III NSCLC patients who complete split course chemoradiation. Objective will be assessed as a binary endpoint of yes/no completion for each patient.

Secondary Outcome Measures

Measure:One-year Overall Survival (OS)
Time Frame:1 year
Safety Issue:
Description:To determine the 1-year overall survival rate
Measure:One-year Progression-Free Survival (PFS) according to RECIST 1.1
Time Frame:1 year
Safety Issue:
Description:To determine the 1-year progression-free survival rate
Measure:One-Year Loco-regional Progression-free Survival (PFS) according to RECIST 1.1
Time Frame:1 year
Safety Issue:
Description:To determine the 1-year loco-regional progression-free survival rate
Measure:Rate of grade 3 and 4 toxicities assessed by CTCAE v 5.0
Time Frame:1 year
Safety Issue:
Description:To determine rate of grade 3 and 4 toxicities with this regimen in the selected patient population

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rush University Medical Center

Trial Keywords

  • Stage III NSCLC
  • Durvalumab
  • Elderly
  • Poor-risk
  • chemoradiation

Last Updated

March 10, 2021