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).
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|ClinicalTrials.gov Identifier: NCT03022409|
Recruitment Status : Completed
First Posted : January 16, 2017
Last Update Posted : March 3, 2021
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Squamous Cell Carcinoma||Drug: Ceralasertib Drug: Olaparib||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Clinical Trial to Investigate Biomarker Effects of Pre-Surgical Treatment With DDR Agents in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) Who Are Planned to Undergo Surgery That is Likely to be Followed by Radiotherapy and/or Chemotherapy.|
|Actual Study Start Date :||September 18, 2017|
|Actual Primary Completion Date :||September 4, 2020|
|Actual Study Completion Date :||September 4, 2020|
AZD6738 (160 mg) tablet twice daily continuous dosing for a minimum of 9 days and a maximum of 21 days.
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.
Other Name: AZD6738
Olaparib (300 mg) tablets administered orally twice daily continuously for a minimum of 9 days and a maximum of 21 days.
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 Name: AZD2281
- Conversion of an immunologically based 25-gene signature from a prognostically unfavourable state to a prognostically favourable state. [ Time Frame: From baseline through Day 31 (Follow up) ]To investigate prognosis-correlated immune activation due to DDR inhibition by monitoring the induction of immunologically relevant genes in tumours of patients treated with study investigational agent(s)
- Transition from a low tumour infiltrating leukocyte (TIL) state (poor prognosis) to a high TIL state (favourable prognosis) shown by TIL enumeration and an increase in CD8+ T-cells [ Time Frame: From baseline through Day 31 (Follow up) ]To investigate the prevalence and localization of TILs associated with prognosis.
- Transition from a low TIL infiltrative state (poor prognosis) to a high TIL infiltrative state (favourable prognosis) shown by TIL enumeration and an increase in CD3+ T-cells [ Time Frame: From baseline through Day 31 (Follow up) ]To investigate the prevalence and localization of tumour infiltrating leukocytes (TILs) associated with prognosis.
- Number of patients with adverse events (AE) / serious adverse events (SAE) [ Time Frame: From time of signature of informed consent throughout the treatment period and including the follow-up period ]Assessment of the safety for each DDR agent in terms of the incidences of the AEs
- Vital signs [ Time Frame: From screening until Day 15 (+ 2 days) ]Assessment of the safety for each DDR agent in terms of the Vital signs
- Clinical chemistry/haematology [ Time Frame: From screening until Day 15 (+ 2 days) ]Assessment of the safety for each DDR agent in terms of the clinical chemistry / haematology assessments
- Number of patients with abnormal findings in Electrocardiograms (ECG) [ Time Frame: At screening and Day 1 ]Assessment of the safety for each DDR agent in terms of the ECG changes. A 12-lead ECG will be performed in triplicate at screening and at a time convenient during the visits (single ECG only required at subsequent visits).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03022409
|United States, Pennsylvania|
|Pittsburgh, Pennsylvania, United States, 15240|
|Toulouse, France, 31300|
|Changhua City, Taiwan, 50006|
|Taipei, Taiwan, 100|
|London, United Kingdom, SE1 9RT|
|Principal Investigator:||Dr. Umamaheshwar Duvvuri||University of Pittsburgh Medical Center (UPMC)|