A Study to Investigate Biomarker Effects of Pre-Surgical Treatment With DNA Damage Repair (DDR) Agents in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC).
Condition: Head and Neck Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Study type: Interventional
Phase: Phase 1

Summary: 
      This biomarker study has been designed to assess the effects of different agents in both
      tumour tissue and peripheral samples to help inform the best combinations of DDR agents with
      immuno-oncology (IO) therapies. In the first instance 2 DDR agents will be assessed
      separately as monotherapy. Additional arms may be added later to evaluate other DDR agents
      and/or DDR and immunotherapy agents in combination or in sequence. The primary objective of
      the study is to investigate immune activation due to DDR inhibition by assessing tumour and
      blood samples of patients treated with study investigational agent(s).
    

Detailed description: 
      Patients are dosed for a minimum of nine days with drug. Surgery or biopsy can then take
      place at any time between Day 10 and Day 21 (depending on when it can be scheduled), but must
      occur with 24 hrs following three consecutive treatment days. During the treatment period,
      safety assessments must be completed at least weekly.

      Follow-up will be completed after surgical resection or biopsy has been completed and can be
      part of standard post-surgery follow-up. If this follow-up visit occurs prior to 30 days
      after the final dose, a further visit or telephone call must be conducted to assess that any
      toxicity has resolved and to check for late toxicity.
    

Intervention name(s): Ceralasertib; Olaparib
Intervention type(s): Drug; Drug
Intervention description(s): Ceralasertib is an oral agent and will be dosed at 160 mg. Ceralasertib tablets should be taken at the same time each day, approximately 12 hours apart (maximum ± 2 hour window) with one glass of water.
Ceralasertib is a potent, selective inhibitor of the serine/threonine-specific protein kinase, ataxia telangiectasia and Rad3-related protein (ATR), with good selectivity against other phosphatidylinositol 3-kinase-related kinase (PIKK) family members.; Olaparib is available as a green film-coated tablet containing 100 mg or 150 mg of Olaparib. Patients will be administered Olaparib orally twice daily at 300 mg bid. The Olaprib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water.
Olaparib (AZD2281, KU-0059436) is a potent Polyadenosine 5'diphosphoribose [poly (ADP ribose)] polymerisation (PARP) inhibitor (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anti-cancer agents.
Other intervention name(s): AZD6738; AZD2281
Intervention MeSH terms: Olaparib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Treatment naïve- or a second tumour; Head and Neck Squamous Cell Carcinoma (HNSCC); DNA Damage Repair (DDR)