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

May 29, 2012 updated by: University College, London

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)

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: olaparib
Given twice daily. Exposure will escalate by daily dose and duration.
Other Names:
  • AZ2281
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of dose limiting toxicities
Time Frame: 6 weeks post completion of treatment
6 weeks post completion of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Complete response rate
Time Frame: 12 weeks post completion of treatment
12 weeks post completion of treatment
Time to loco-regional progression
Time Frame: 2 years post completion of treatment
2 years post completion of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Martin D Forster, MBBS, University College London Hospitals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 7, 2022

Primary Completion

December 7, 2022

Study Completion

December 7, 2022

Study Registration Dates

First Submitted

December 9, 2011

First Submitted That Met QC Criteria

December 12, 2011

First Posted (Estimate)

December 13, 2011

Study Record Updates

Last Update Posted (Estimate)

May 30, 2012

Last Update Submitted That Met QC Criteria

May 29, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-023599-24
  • 62346992 (Registry Identifier: ISRCTN)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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