Phase I Study of Olaparib Combined With Cisplatin-based Chemoradiotherapy to Treat Locally Advanced Head and Neck Cancer

NCT02308072 | Completed Phase 1 DMC

• 2 other identifiers: UCL/13/06962014-002525-35
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Head and Neck Cancer

Keywords

Squamous Cell Carcinoma; Head and Neck Cancer; Locally Advanced; Olaparib; Cisplatin; IMRT; Chemoradiotherapy; PARP; HNSCC

Outcome Measures

Primary Outcomes (1)

• Occurrence of Dose Limiting Toxicity

  Detailed adverse event monitoring will be conducted according to CTCAE v4.03. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that is considered to be trial treatment related and commencing anytime during the DLT evaluation period (from start of week 1 of olaparib + CRT until 6 weeks after end of olaparib + CRT).

  From start of week 1 to 6 weeks after end of combination treatment (combination treatment = 7 weeks)

Secondary Outcomes (6)

• Occurrence and Severity of Adverse Events

  From date of registration until 12 weeks after completion of trial treatment

• Best Overall Response

  Determined from imaging/scans performed pre-registration, during treatment and follow-up until disease progression or up to 2 years from date of registration

• Time to Loco-Regional Progression

  From date of registration to date of documented disease progression, assessed up to 2 years from date of registration

• Time to Progression

  From date of registration to date of documented objective disease progression

• Progression Free Survival

  From date of registration to date of documented disease progression or death from any cause, whichever comes first. Assessed up to 2 years from date of registration.

Study Arms (1)

Olaparib + Cisplatin + IMRT

EXPERIMENTAL

Olaparib: 50, 100, 150 or 200 mg twice a day for between 3-5 sequential days, depending on cohort allocation, in combination with Cisplatin: 35 mg/m\^2 on day 1, and IMRT: 2 Gy radiotherapy given on days 1-5 Treatment will start on day 1 of every week. Patients will receive up to 7 weeks of combination chemotherapy and radiotherapy treatment.

Drug: Olaparib; Drug: Cisplatin; Radiation: IMRT

Interventions

Olaparib DRUG

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.

Olaparib + Cisplatin + IMRT

Cisplatin DRUG

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)

Olaparib + Cisplatin + IMRT

IMRT RADIATION

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)

Olaparib + Cisplatin + IMRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed high-risk locally advanced HNSCC, patients who would normally be offered cisplatin-based radical chemoradiotherapy
• Estimated life expectancy of at least 16 weeks
• WHO performance status 0 or 1
• Aged ≥18 years
• Adequate bone marrow function: absolute neutrophils grade 0 or 1, platelets grade 0 or 1, haemoglobin grade 0 or 1
• 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)
• Adequate liver function: Serum bilirubin grade 0 or 1, AST or ALT grade 0 or 1
• Patients must be able to swallow olaparib tablets
• Willing to use contraception for the duration of the trial treatment and for six months after completion of treatment
• Able to give informed consent
• Patients willing and able to comply with the protocol for the duration of the study

You may not qualify if:

• 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)
• Confirmed distant metastatic disease
• Previous chemotherapy or radiotherapy for the treatment of HNSCC tumour
• Previous therapy with a PARP inhibitor
• Chemotherapy, immunotherapy or radiotherapy within 28 days prior to registration
• 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
• Women who are pregnant or lactating
• Pre-existing gastrointestinal disorders that may interfere with the delivery or absorption of olaparib
• 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.
• 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
• Known hepatitis B or C infection (testing for Hepatitis and HIV for the trial is not mandatory)
• Immunocompromised patients (e.g. known HIV positive status)
• Active uncontrolled infection
• The current use of drugs which are known to inhibit or induce CYP3A4
• Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator
• AstraZeneca: collaborator

Study Sites (3)

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Velindre Cancer Centre

Wales, CF14 2TL, United Kingdom

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

olaparib; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Martin Forster

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 4, 2014
• Study Start: September 1, 2015
• Primary Completion: June 1, 2020
• Study Completion: April 24, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

GB (3)