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

This study has been withdrawn prior to enrollment.
(Study stopped due to issues surrounding development and formulation of olaparib)
Information provided by (Responsible Party):
University College, London Identifier:
First received: December 9, 2011
Last updated: May 29, 2012
Last verified: May 2012
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.

Condition Intervention Phase
Carcinoma, Squamous Cell
Drug: olaparib
Drug: cisplatin
Radiation: Intensity Modulated Radiotherapy
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:

Further study details as provided by University College, London:

Primary Outcome Measures:
  • Frequency of dose limiting toxicities [ Time Frame: 6 weeks post completion of treatment ]

Secondary Outcome Measures:
  • Complete response rate [ Time Frame: 12 weeks post completion of treatment ]
  • Time to loco-regional progression [ Time Frame: 2 years post completion of treatment ]

Enrollment: 0
Arms Assigned Interventions
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 Name: 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.

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01491139

Sponsors and Collaborators
University College, London
Principal Investigator: Martin D Forster, MBBS University College London, UK
  More Information

Responsible Party: University College, London Identifier: NCT01491139     History of Changes
Other Study ID Numbers: 2010-023599-24
62346992 ( Registry Identifier: ISRCTN )
Study First Received: December 9, 2011
Last Updated: May 29, 2012

Keywords provided by University College, London:
Biomarkers, pharmacological
Genetic Markers
Poly(ADP-ribose) Polymerases
AZD 2281
Radiotherapy, Intensity-Modulated
Head and Neck

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 27, 2017