Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck (ORCA)
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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) |
- Frequency of dose limiting toxicities [ Time Frame: 6 weeks post completion of treatment ] [ Designated as safety issue: Yes ]
- 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)
olaparib plus chemoradiotherapy (8 weeks)
|
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 |
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 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, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell |
Neoplasms by Site Cisplatin Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 18, 2013