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

Carcinoma, Squamous Cell Clinical Trial

— ORCA  

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01491139
• Other study ID #: 2010-023599-24
• Secondary ID: 62346992
• Status: Withdrawn
• Phase: Phase 1
• First received: December 9, 2011
• Last updated: May 29, 2012

Study information

• Verified date: May 2012
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms

Intervention

Drug:
• olaparib
Given twice daily. Exposure will escalate by daily dose and duration.
• cisplatin
Dose will be 35mg/m2 i.v. once weekly.

Radiation:
• Intensity Modulated Radiotherapy
Total dose will be 70Gy in 35 fractions over 7 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	AstraZeneca

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of dose limiting toxicities		6 weeks post completion of treatment	Yes
Secondary	Complete response rate		12 weeks post completion of treatment	No
Secondary	Time to loco-regional progression		2 years post completion of treatment	No