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Trial Title:
Phase I Study of Olaparib Combined With Cisplatin-based Chemoradiotherapy to Treat Locally Advanced Head and Neck Cancer
NCT ID:
NCT02308072
Condition:
Head and Neck Cancer
Conditions: Official terms:
Head and Neck Neoplasms
Olaparib
Conditions: Keywords:
Squamous Cell Carcinoma
Head and Neck Cancer
Locally Advanced
Olaparib
Cisplatin
IMRT
Chemoradiotherapy
PARP
HNSCC
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olaparib
Description:
50 mg, 100 mg, 150 mg or 200 mg taken twice daily (depending on dose under investigation
at time of registration) on days 1-3, 1-4 or 1-5 (depending on allocation of treatment
schedule) of each week of treatment.
Arm group label:
Olaparib + Cisplatin + IMRT
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
35 mg/m^2 IV on day 1 of each week of treatment during radiotherapy for a total of 7
weeks (total overall dose 245 mg/m^2)
Arm group label:
Olaparib + Cisplatin + IMRT
Intervention type:
Radiation
Intervention name:
IMRT
Description:
2 Gy delivered in 35 fractions, on days 1-3, 1-4 or 1-5 each week for up to 7 weeks
(total overall dose delivered 70 Gy)
Arm group label:
Olaparib + Cisplatin + IMRT
Summary:
The phase I trial aims to determine the recommended phase II dose (RP2D) and schedule of
olaparib in combination with standard cisplatin-based chemoradiotherapy, in patients with
high-risk locally advanced squamous cell carcinoma of the head and neck (HNSCC), by
assessing the safety and tolerability of the treatment combination.
Detailed description:
ORCA-2 is a phase I trial in patients with locally advanced, with or without metastatic
nodal disease.
Patients will receive olaparib (a PARP inhibitor) in combination with standard
cisplatin-based chemotherapy and intensity modulated radiotherapy (IMRT).
Olaparib, cisplatin and radiotherapy will be given in combination every week for a
maximum of 7 weeks. Prior to starting combination treatment, olaparib will be started 7
days before the first week of combination treatment. Olaparib will be given twice daily
on days 1-3 of each week of treatment (either alone during week 0 or in combination with
chemotherapy and radiotherapy during weeks 1-7). Cisplatin will be started on day 1 of
each week, and given once a week during radiotherapy treatment for a total of 7 weeks.
Radiotherapy will be delivered on days 1-5 of each week using IMRT, for a total of 7
weeks.
The phase I trial aims to determine the recommended phase II dose of olaparib (50mg,
100mg, 150mg or 200mg bd) - the dose of olaparib patients receive will depend on the dose
under investigation at the time of patient registration.
Dose escalation will be guided by the two-dimensional dose escalation design called
Product of Independent Beta Probabilities escalation (PIPE). It will recommend the choice
of dose/duration combination cohort of olaparib for subsequent patients by estimating the
contour that divides dose/duration combination cohorts to be those above the target
toxicity rate (equal to 33%) and those below. The recommended phase II cohort(s) are
those that have been experimented on during the trial and are also closest to (but not
above) the estimated contour calculated using all trial data.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed high-risk locally advanced HNSCC, patients who would
normally be offered cisplatin-based radical chemoradiotherapy
2. Estimated life expectancy of at least 16 weeks
3. WHO performance status 0 or 1
4. Aged ≥18 years
5. Adequate bone marrow function: absolute neutrophils grade 0 or 1, platelets grade 0
or 1, haemoglobin grade 0 or 1
6. Adequate renal function: Creatinine grade 0 or 1, Calculated GFR ≥60 mL/min (if
calculated value is <60 mL/min then an isotope GFR assessment should be performed or
an estimation from 24h urine collection)
7. Adequate liver function: Serum bilirubin grade 0 or 1, AST or ALT grade 0 or 1
8. Patients must be able to swallow olaparib tablets
9. Willing to use contraception for the duration of the trial treatment and for six
months after completion of treatment
10. Able to give informed consent
11. Patients willing and able to comply with the protocol for the duration of the study
Exclusion Criteria:
1. Head & neck cancers of the following types: Nasopharyngeal and paranasal sinus
tumours, Oral squamous cell carcinomas (tumours of the oral cavity), Low risk Human
Papilloma Virus positive oropharyngeal tumours (tonsillar and tongue base tumours)
2. Confirmed distant metastatic disease
3. Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
4. Previous therapy with a PARP inhibitor
5. Chemotherapy, immunotherapy or radiotherapy within 28 days prior to registration
6. Prior history of malignancy, except for basal cell or squamous cell carcinoma of the
skin, carcinoma in situ of the cervix, breast or prostate. Patient must have been
free of malignancy for a period of 3 years prior to first dose of trial drug
7. Women who are pregnant or lactating
8. Pre-existing gastrointestinal disorders that may interfere with the delivery or
absorption of olaparib
9. Grade 3 or 4 peripheral neuropathy - If considered significant by the treating
clinician a lower grade neuropathy may be considered as exclusion criterion
10. Significant hearing difficulties or tinnitus (deaf patients can be included) -
Whilst not excluded, patients with mildly impaired hearing or tinnitus must be made
aware of potential ototoxicity and may choose not to be included. If included, it is
recommended that audiograms be carried out at baseline.
11. Any serious and/or unstable pre-existing medical, psychiatric or other condition
that, in the treating clinician's judgment, could interfere with patient safety or
obtaining informed consent
12. Known hepatitis B or C infection (testing for Hepatitis and HIV for the trial is not
mandatory)
13. Immunocompromised patients (e.g. known HIV positive status)
14. Active uncontrolled infection
15. The current use of drugs which are known to inhibit or induce CYP3A4
16. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or
family history of long QT syndrome.
17. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
18. Patients with a known hypersensitivity to olaparib or any of the excipients of the
product.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Guy's and St Thomas' NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
University College London Hospitals NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Facility:
Name:
Velindre Cancer Centre
Address:
City:
Wales
Zip:
CF14 2TL
Country:
United Kingdom
Start date:
September 2015
Completion date:
February 2025
Lead sponsor:
Agency:
University College, London
Agency class:
Other
Collaborator:
Agency:
Cancer Research UK
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
University College, London
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02308072