NCT01491139

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.

Trial Health

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 9, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 13, 2011

Completed
Last Updated

May 30, 2012

Status Verified

May 1, 2012

First QC Date

December 9, 2011

Last Update Submit

May 29, 2012

Conditions

Keywords

RadiotherapyBiomarkers, pharmacologicalPharmacokineticsGenetic MarkersCisplatinPoly(ADP-ribose) PolymerasesAZD 2281Radiotherapy, Intensity-ModulatedHead and NeckChemoradiotherapySCC

Outcome Measures

Primary Outcomes (1)

  • Frequency of dose limiting toxicities

    6 weeks post completion of treatment

Secondary Outcomes (2)

  • Complete response rate

    12 weeks post completion of treatment

  • Time to loco-regional progression

    2 years post completion of treatment

Study Arms (1)

single arm

EXPERIMENTAL

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: olaparibDrug: cisplatinRadiation: Intensity Modulated Radiotherapy

Interventions

Given twice daily. Exposure will escalate by daily dose and duration.

Also known as: AZ2281
single arm

Dose will be 35mg/m2 i.v. once weekly.

single arm

Total dose will be 70Gy in 35 fractions over 7 weeks.

single arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

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),
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Carcinoma, Squamous Cell

Interventions

olaparibCisplatinRadiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsRadiotherapy, ConformalRadiotherapy, Computer-AssistedRadiotherapyTherapeutics

Study Officials

  • Martin D Forster, MBBS

    University College London Hospitals

    PRINCIPAL INVESTIGATOR
0

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 9, 2011

First Posted

December 13, 2011

Last Updated

May 30, 2012

Record last verified: 2012-05