AZD1775 Combined With Olaparib in Patients With Refractory Solid Tumors
Condition: Refractory Solid Tumours; Relapsed Small Cell Lung Cancer (SCLC)
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this Phase 1b, multi-centre, dose escalation study is to find the maximum
      tolerated dose (MTD) of AZD1775 combined with olaparib in patients with refractory solid
      tumours
    

Detailed description: 
      This is a Phase Ib, multi-centre study of AZD1775 combined with olaparib administered orally
      in patients with refractory solid tumours, or as combination therapy for relapsed small-cell
      lung cancer (SCLC). There are 2 parts to the study:

      Part A: Dose Escalation Part B: Dose Expansion

      In Part A, patients with refractory solid tumours will be assessed for safety, tolerability,
      and pharmacokinetics (PK) of AZD 1775 when combined with olaparib. Different dose levels will
      be administered to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D).

      The dose expansion part (Part B) will further explore the safety, PK, and preliminary
      efficacy of the AZD1775 RP2D and dosing schedule for the treatment of patients with SCLC who
      previously had a confirmed response (either a Complete Response or Partial Response) to
      first-line platinum therapy and then relapsed. Patients who progressed whilst on
      platinum-containing therapy (platinum refractory) are not permitted to enter the study..

      An olaparib pharmacokinetic (PK) sub-study will precede the combined treatment with AZD1775
      and olaparib for all patients in Part A. In the sub-study single agent olaparib will be given
      orally BID for 3 or 5 consecutive days and venous blood samples will be collected on Day 3 or
      Day 5 as appropriate for assessment of the multiple dose pharmacokinetics of single agent
      olaparib. Patients will experience a short gap in treatment (approximately 4-5 days) between
      Day 3 or Day 5 of the olaparib PK sub-study and Cycle 1 Day 1 of the combination treatment.

      Patients will continue to receive treatment with AZD1775 and Olaparib until disease
      progression, intolerable toxicity, or discontinuation criteria have been met.
    

Intervention name(s): AZD1775; Olaparib
Intervention type(s): Drug; Drug
Intervention description(s): AZD1775 will be given twice daily (PO BID) over 3 days (6 doses) on Days 1-3 and 8-10 of each 21 day cycle combined with olaparib PO BID on Days 1-14 of each 21 day cycle.
Olaparib will be given orally BID on Days 1-14.; AZD1775 will be given twice daily (PO BID) over 5 days (10 doses) on Days 1-5 and 8-12 of each 21 day cycle combined with olaparib PO BID on Days 1-14 of each 21 day cycle.
Olaparib will be given orally BID on Days 1-14.
Intervention MeSH terms: Olaparib; Adavosertib
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: AZD1775; Olaparib; AZD1775 plus Olaparib; Refractory Solid Tumours; Small Cell Lung Cancer (SCLC); Relapsed Small Cell Lung Cancer