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ADePT

Name of Study: Accelerating the Development and implementation of Personalised Treatments of DNA Damage Response agents and radiotherapy +/- immunotherapy for head and neck squamous cell cancer

Acronym: ADePT-DDR

Summary and Eligibility:

The ADePT-DDR trial has been set up to evaluate the safety and efficacy of different DNA Damage Repair (DDR) agents together with radiotherapy in patients with head and neck squamous cell carcinoma being treated curatively. The purpose of this study is to determine maximum tolerated dose of Ceralasertib in combination with radiotherapy for HNSCC patients.

If eligible for the trial, patients will be registered to the experimental arm (Ceralasertib with radiotherapy) or the Control Group (radiotherapy only).

General Inclusion Criteria:

  • Patients aged ≥ 18 years of age, and able to give consent.
  • Primary head and neck squamous cell carcinoma (laryngeal, hypopharyngeal, oropharyngeal) with recommendation by consultant for treatment with radical radiotherapy.
  • Not had previous treatment for head and neck cancer.
  • At least one measurable lesion at baseline by CT scan or MRI.
  • ECOG performance status of 0 or 1 prior to registration.
  • Patients must have normal organ and bone marrow function prior to registration.
  • Females must not be breast feeding and have a negative urine/serum pregnancy test upon trial entry.
  • Willingness to comply with trial protocol.
  • For the optional biomarker research, patients must provide informed consent for biomarker research.

General Exclusion Criteria:

  • Tumour staging outside of protocol parameters.
  • A diagnosis of ataxia telangiectasia or other radiosensitivity syndrome.
  • Cytotoxic chemotherapy, hormonal or non-hormonal targeted therapy within 21 days of treatment start is not permitted.
  • Any unresolved toxicities from prior therapy ≥ Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade 2 (except alopecia and CTCAE grade 2 neuropathy).
  • Any of the following cardiac diseases currently or within the last 6 months:
  1. Unstable angina pectoris
  2. Congestive heart failure or known reduced left ventricular ejection fraction (LVEF) < 50%
  3. Acute myocardial infarction
  4. Conduction abnormality not controlled with pacemaker or medication
  5. Significant ventricular or supraventricular arrhythmias
  6. Patients at risk of brain perfusion problems.
  7. Uncontrolled hypertension (CTCAE v5.0, grade 2+) requiring clinical intervention.
  • Mean resting corrected QT interval (QTc) >470 msec for females and >450 for men.
  • Patients with relative hypotension (<90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of > 20 mm Hg.
  • Concomitant use of known potent cytochrome P(CYP)3A and potent cytochrome P450 inducers.
  • As judged by the Investigator, any evidence of severe/uncontrolled systemic diseases that places the patient at unacceptable risk of toxicity or non-compliance. Screening for chronic conditions is not required.
  • Known hypersensitivity to Ceralasertib.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of Ceralasertib.

Status: Open

Lead Centre: Queen Elizabeth Hospital, Birmingham

Study Coordinator:

Jasmin Cheang

ADePT-DDR Trial Coordinator

Cancer Research UK Clinical Trials Unit (CRCTU)

Institute of Cancer and Genomic Sciences

University of Birmingham

Edgbaston

Birmingham B15 2TT

 

Trial Schema

ADePT Trial Schema