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Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck (ORCA)

Primary Purpose

Carcinoma, Squamous Cell

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
olaparib
cisplatin
Intensity Modulated Radiotherapy
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Squamous Cell focused on measuring Radiotherapy, Biomarkers, pharmacological, Pharmacokinetics, Genetic Markers, Cisplatin, Poly(ADP-ribose) Polymerases, AZD 2281, Radiotherapy, Intensity-Modulated, Head and Neck, Chemoradiotherapy, SCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    single arm

    Arm Description

    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

    Outcomes

    Primary Outcome Measures

    Frequency of dose limiting toxicities

    Secondary Outcome Measures

    Complete response rate
    Time to loco-regional progression

    Full Information

    First Posted
    December 9, 2011
    Last Updated
    May 29, 2012
    Sponsor
    University College, London
    Collaborators
    AstraZeneca
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01491139
    Brief Title
    Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck
    Acronym
    ORCA
    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)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2012
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Study stopped due to issues surrounding development and formulation of olaparib
    Study Start Date
    undefined (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University College, London
    Collaborators
    AstraZeneca

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Carcinoma, Squamous Cell
    Keywords
    Radiotherapy, Biomarkers, pharmacological, Pharmacokinetics, Genetic Markers, Cisplatin, Poly(ADP-ribose) Polymerases, AZD 2281, Radiotherapy, Intensity-Modulated, Head and Neck, Chemoradiotherapy, SCC

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    single arm
    Arm Type
    Experimental
    Arm Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    olaparib
    Other Intervention Name(s)
    AZ2281
    Intervention Description
    Given twice daily. Exposure will escalate by daily dose and duration.
    Intervention Type
    Drug
    Intervention Name(s)
    cisplatin
    Intervention Description
    Dose will be 35mg/m2 i.v. once weekly.
    Intervention Type
    Radiation
    Intervention Name(s)
    Intensity Modulated Radiotherapy
    Intervention Description
    Total dose will be 70Gy in 35 fractions over 7 weeks.
    Primary Outcome Measure Information:
    Title
    Frequency of dose limiting toxicities
    Time Frame
    6 weeks post completion of treatment
    Secondary Outcome Measure Information:
    Title
    Complete response rate
    Time Frame
    12 weeks post completion of treatment
    Title
    Time to loco-regional progression
    Time Frame
    2 years post completion of treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Martin D Forster, MBBS
    Organizational Affiliation
    University College London Hospitals
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Phase I Study of Olaparib With Cisplatin Based Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

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