Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

NCT ID: NCT01491139

Last Updated: 2012-05-30

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL

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.

Conditions

Carcinoma, Squamous Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

single arm

All patients will receive induction chemotherapy (cisplatin and 5-FU), followed by cisplatin chemotherapy and radiotherapy in addition to oral olaparib.

Induction chemotherapy (21 day cycle)

• Drug: cisplatin 80mg/m2 (day 1)
• Drug: 5-FU (fluorouracil) 1000mg/m2/day (day 1-4 continuous infusion)

olaparib plus chemoradiotherapy (8 weeks)

• Drug: olaparib
• Drug: Cisplatin
• Radiation

Group Type: EXPERIMENTAL

olaparib

Intervention Type: DRUG

Given twice daily. Exposure will escalate by daily dose and duration.

cisplatin

Intervention Type: DRUG

Dose will be 35mg/m2 i.v. once weekly.

Intensity Modulated Radiotherapy

Intervention Type: RADIATION

Total dose will be 70Gy in 35 fractions over 7 weeks.

Interventions

olaparib

Given twice daily. Exposure will escalate by daily dose and duration.

Intervention Type: DRUG

cisplatin

Dose will be 35mg/m2 i.v. once weekly.

Intervention Type: DRUG

Intensity Modulated Radiotherapy

Total dose will be 70Gy in 35 fractions over 7 weeks.

Intervention Type: RADIATION

Other Intervention Names

AZ2281

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin D Forster, MBBS

Role: PRINCIPAL_INVESTIGATOR

University College London Hospitals

Other Identifiers

62346992

Identifier Type: REGISTRY

Identifier Source: secondary_id

2010-023599-24

Identifier Type: -

Identifier Source: org_study_id