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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This study has been withdrawn prior to enrollment.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)
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01491139
First received: December 9, 2011
Last updated: May 29, 2012
Last verified: May 2012
  Purpose

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: Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Complete response rate [ Time Frame: 12 weeks post completion of treatment ] [ Designated as safety issue: No ]
  • Time to loco-regional progression [ Time Frame: 2 years post completion of treatment ] [ Designated as safety issue: No ]

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01491139

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

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01491139     History of Changes
Other Study ID Numbers: 2010-023599-24, 62346992
Study First Received: December 9, 2011
Last Updated: May 29, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Cisplatin
Antineoplastic Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014