Clinical trial NCT01491139: Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck
Official title: A Phase I/II Study of Olaparib in Addition to Cisplatin Based Concurrent Chemoradiotherapy for Patients With High Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Carcinoma, Squamous Cell
Keywords: Radiotherapy
Biomarkers, pharmacological
Pharmacokinetics
Genetic Markers
Cisplatin
Poly(ADP-ribose) Polymerases
AZD 2281
Radiotherapy, Intensity-Modulated
Head and Neck
Chemoradiotherapy
SCC
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2011-12-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to find the safe dose and best dosing schedule of olaparib to give in combination with cisplatin based chemoradiotherapy (CRT) in patients with locally advanced head and neck cancer. The dose decided on in this part of the study will become the recommended dose for the randomised Phase II trial.

Detailed description: This is a dose escalating Phase I/II trial evaluating the safety and tolerability of the addition of olaparib to CRT in high risk locally advanced human papillomavirus (HPV) negative Squamous Cell Carcinoma of the Head and Neck (HNSCC). A fixed dose of weekly cisplatin and intensity-modulated radiation therapy (IMRT) will be used, with doses of olaparib escalating for consecutive days and both dose level and duration will be increased through each cohort.

This Phase I trial will assess how olaparib, a poly ADP ribose polymerase (PARP) inhibitor is tolerated when added to standard chemoradiotherapy treatment.

Patients will be recruited from sites in the UK only.

A placebo controlled, randomised Phase II trial will follow once the recommended dose and schedule of olaparib has been established.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed high risk, locally advanced HNSCC patients (TNM staging: T-any N2/3 M0, bulky T3 or T4 N-any M0) who would normally be offered cisplatin-based radical chemoradiotherapy
* Estimated life expectancy of at least 12 weeks
* WHO performance status of 0 or 1
* Aged ≥18 years of age
* Adequate major organ function
* Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
* Able to give informed consent
* Willing and able to comply with the protocol for the duration of the study

Exclusion Criteria:

* Head \& neck cancers of the following types:
* Nasopharyngeal and paranasal sinus tumours,
* Oral squamous cell carcinomas (tumours of the oral cavity),
* Human Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
* Confirmed distant metastatic disease
* Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
* Previous therapy with a PARP inhibitor
* Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
* Grade 3 or 4 peripheral neuropathy
* Significant hearing difficulties or tinnitus (deaf patients can be included)
* The current use of drugs which are known to inhibit or induce CYP3A4

Primary outcomes:
measure: Frequency of dose limiting toxicities
timeFrame: 6 weeks post completion of treatment
Secondary outcomes:
measure: Complete response rate
timeFrame: 12 weeks post completion of treatment
measure: Time to loco-regional progression
timeFrame: 2 years post completion of treatment
Other outcomes:
Locations:
Study officials:
affiliation: University College London Hospitals
name: Martin D Forster, MBBS
role: PRINCIPAL_INVESTIGATOR
References: