A Phase II, Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer
Condition: Platinum Refractory Extensive-Stage Small Cell Lung Carcinoma
MeSH terms: Carcinoma; Lung Neoplasms; Small Cell Lung Carcinoma
Study type: Interventional
Phase: Phase 2

Summary: 
      Study design This is a Phase II, open-label, multi-drug, multi-center, multi-arm,
      signal-searching study in patients with extensive-stage small-cell lung cancer (SCLC) who
      have refractory or resistant disease from prior platinum-based chemotherapy.
    

Detailed description: 
      This study is modular in design, allowing evaluation of the preliminary efficacy, safety,
      tolerability, and immunogenicity of novel combinations of immunotherapies and/or
      deoxyribonucleic acid (DNA) damage repair inhibitors in patients with platinum refractory or
      resistant extensive-stage-disease SCLC. Patients who have progressive disease (PD) during
      first-line platinum-based chemotherapy (platinum refractory) or PD within 90 days after
      completing first-line platinum-based chemotherapy (platinum resistant) will be enrolled to
      the study. The primary objective of the study is to assess the preliminary efficacy of each
      treatment arm based on objective response rate (ORR).

      This study consists of a number of arms (sub-studies), each evaluating the efficacy, safety,
      and tolerability of a specific agent or combination. This study was initially open with 2
      arms (Arms A and B), and additional arms may open, provided there is compelling rationale for
      the combination and safe and tolerable doses and schedules have been determined from ongoing
      Phase I studies. There are 2 pre-defined arms:

      A. Durvalumab + tremelimumab followed by durvalumab monotherapy B. AZD1775 + carboplatin
      (CBDP)

      Further arm was added in amendment 3:

      C. AZD6738 + olaparib Amendment #4 was updated with possibility to allow expansion of any
      arm, to a total of 40 eligible subjects, based on Review Committee assessment of data from
      the first 20 subjects (from Stage 1 and Stage 2). Currently Arm A will enroll 20 additional
      patients into expansion.
    

Intervention name(s): Durvalumab and Tremelimumab; AZD1775 and carboplatin (CBPT); AZD6738 and olaparib
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Durvalumab + tremelimumab via intravenous (IV) infusion every 4 weeks (q4w), starting on Week 0, for up to a total of 4 months (4 cycles) followed by durvalumab monotherapy via IV infusion q4w, starting on Week 16 until PD, or for other discontinuation criteria.; AZD1775 twice daily (oral) for 2.5 days from Day 1 + CBDP area under the curve 5 (Day1) (IV); every 3 weeks.; AZD6738 once a day (oral) for 7 days from Day 1 + olaparib twice a day(oral) for 28 days from Day 1, every 4 weeks
Intervention MeSH terms: Carboplatin; Durvalumab; Olaparib; Tremelimumab; Adavosertib
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Platinum Refractory Extensive-Stage Carcinoma, Small Cell Lung; Platinum Refractory Extensive-Stage Oat Cell Carcinoma of Lung; Platinum Refractory Extensive-Stage Oat Cell Lung Cancer; Platinum Refractory Extensive-Stage Small Cell Cancer Of The Lung; Platinum Refractory Extensive-Stage Small Cell Lung Cancer