Clinical Trial 21534

• Overview

  Study Title:

  Randomized Phase III Trial of MEDI4736 (Durvalumab) as Concurrent and Consolidative Therapy or Consolidative Therapy Alone for Unresectable Stage 3 NSCLC

  Summary:

  This phase III trial studies how well an antibody (durvalumab) with chemotherapy and radiation therapy (chemoradiation) works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery (unresectable).

  Objective:

  Primary Objectives * The primary objective of this trial is to evaluate whether there is an improvement in overall survival with concomitant chemotherapy/radiation therapy/MEDI4736 (durvalumab) followed by one year (12 cycles) of MEDI4736 (durvalumab) as compared to concomitant chemotherapy/radiation followed by one year (12 cycles) of MEDI4736 (durvalumab). Secondary Objectives * Best objective response rate (ORR): To evaluate the difference in response using RECIST 1.1 criteria to assess whether or not MEDI4736 (durvalumab) added to concomitant chemo/radiation results in an improvement in response rates. * Progression-free survival (PFS): To evaluate any difference in PFS with concomitant chemotherapy/radiation therapy/MEDI4736 (durvalumab) followed by one year (12 cycles) of MEDI4736 (durvalumab) as compared to concomitant chemotherapy/radiotherapy followed by one year of MEDI4736 (durvalumab). * Recurrence patterns (RP) (local vs distant): To evaluate whether the incidence of recurrence and recurrence pattern is affected by giving MEDI4736 (durvalumab) during chemo/radiation. Local recurrence will be defined as any recurrence confined to the ipsilateral lung or the N1-N3 nodal areas. All other recurrences will be considered distal recurrences. * Toxicity: To evaluate any difference in toxicity when MEDI4736 (durvalumab) is added to concomitant chemo/radiation using the CTCAE.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy; Radiotherapy

  Medications:

  AMP-514 (Durvalumab); Alimta (Pemetrexed); Durvalumab (); MEDI4736 (Durvalumab); Paraplatin (carboplatin); Pemetrexed (); Radiotherapy (); Taxol (paclitaxel); carboplatin (); cisplatin (); etoposide (); paclitaxel ()

• Inclusion Criteria

  Inclusion Criteria: STEP 1 INCLUSION CRITERIA
  • Patient must have one of the following: (a) Newly diagnosed stage IIIA/B/C non-small cell lung cancer (NSCLC) (per the American Joint Committee on Cancer [AJCC] 8th edition) that is unresectable and is histologically and/or cytologically confirmed (b) Nodal recurrence after surgery for early stage NSCLC
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patient must have a body weight > 30 kg
  • Patient must not have unintentional weight loss > 10% within 30 days prior to registration
  • Patient must have a baseline electrocardiography (ECG) obtained within 6 weeks prior to registration.
  • Patient must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Baseline imaging assessments and measurements used to evaluate all measurable or non-measurable sites of disease must be done within 4 weeks prior to registration
  • Lab values as defined per protocol
  • Patient must have pulmonary function tests (PFTs) with both forced expiratory volume in 1 second (FEV1) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% of predicted, obtained within 5 months prior to registration.
  • Patient is expected to have lung volume (V)20 of => Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met: (a) No prior chemotherapy or radiation was ever administered for this lung cancer originally or for recurrence prior to entering this protocol (b) Prior curative-intent surgery was at least 90 days prior to the nodal recurrence (c) No prior radiation was administered to the region of study cancer that would cause overlap of treatment fields
  • Patients who are human immunodeficiency virus (HIV) positive may participate in the study IF they meet all of the following eligibility requirements: (a) They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective (b) They must have a CD4 count of greater than 250 cells/mcL, within 6 months of registration (c) They must not be receiving prophylactic therapy for an opportunistic infection
  • Patients with a prior or concurrent 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 must not have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
  • Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
  • All patients of childbearing potential must have a negative blood test or urine study, with a minimum sensitivity 50 mlU/L or equivalent units of human chorionic gonadotropin (HCG), within 7 days prior to registration to rule out pregnancy. A patient of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months)
  • Additional criteria apply

• Exclusion Criteria

  Exclusion Criteria: STEP 1 EXCLUSION ELIGIBILITY CRITERIA - CONCURRENT THERAPY
  • Patient must not have any active, known or suspected autoimmune disease and neuromuscular paraneoplastic syndromes including, but not limited to myasthenia gravis, Lambert-Eaton myasthenic syndrome, limbic encephalitis, myositis, Guillain-Barré, systemic lupus erythematosus, and systemic sclerosis. Patients with type I diabetes mellitus requiring insulin, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are eligible
  • Patient must not have a history of active hepatitis B (chronic or acute) or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for hepatitis C virus ribonucleic acid (HCV RNA)
  • Patient must not have a known active tuberculosis infection
  • Patient must not have any severe infections within 4 weeks prior to registration including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Patient must not have signs or symptoms of severe infection (sepsis) within 2 weeks prior registration
  • Patient must not have been treated with systemic immunostimulatory agents (including but not limited to interferon-a [IFN-a], interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to registration; or treated with an investigational agent within 4 weeks prior to registration (or within five half-lives of the investigational agent, whichever is longer)
  • Patient must not have a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patient must not have been treated with systemic immunosuppressive medications (equivalent to > 10 mg prednisone per day) or other immunosuppressive medications within 7 days of registration. Inhaled or topical steroids and adrenal replacement steroid doses equivalent to > 10 mg prednisone per day are permitted in the absence of active autoimmune disease
  • Patient must not have had a prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • Patient must not have a history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan within 4 weeks of registration
  • Patient must not have had any prior systemic treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
  • Patient with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment and severity of cardiac symptoms. Symptoms should be stable over the past 3 months. Specifically, patient must not have coronary artery bypass grafting, myocardial infarction, acute coronary syndrome severe/unstable angina, stroke, transient ischemic attack, or heart failure hospitalization within 3 months prior to registration
  • Additional Criteria Apply

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