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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01491139
Recruitment Status : Withdrawn (Study stopped due to issues surrounding development and formulation of olaparib)
First Posted : December 13, 2011
Last Update Posted : May 30, 2012
Information provided by (Responsible Party):
University College, London

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.

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

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  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (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 the National Library of Medicine

U.S. FDA Resources

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 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.

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

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

Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01491139

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

Responsible Party: University College, London Identifier: NCT01491139     History of Changes
Other Study ID Numbers: 2010-023599-24
62346992 ( Registry Identifier: ISRCTN )
First Posted: December 13, 2011    Key Record Dates
Last Update Posted: May 30, 2012
Last Verified: May 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