Clinical Trials /

The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer

NCT01706939

Description:

This trial aims to directly compare a reduced radiation dose to the standard of care in HPVOPC for non-inferiority, thus allowing for direct comparison of outcomes between the two groups. The study hypothesis is that LRC and PFS at 3 years for reduced dose CRT are non-inferior to standard dose CRT.

Related Conditions:
  • Nasopharyngeal Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

The Quarterback Trial: Reduced Dose <span class="go-doc-concept go-doc-intervention">Radiotherapy</span> for HPV+ Oropharynx <span class="go-doc-concept go-doc-disease">Cancer</span>

Title

  • Brief Title: The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
  • Official Title: The Quarterback Trial: A Randomized Phase III Clinical Trial Comparing Reduced and Standard Radiation Therapy Doses for Locally Advanced HPV Positive Oropharynx Cancer
  • Clinical Trial IDs

    NCT ID: NCT01706939

    ORG ID: GCO 12-1050

    NCI ID: HS 12-00359

    Trial Conditions

    Squamous Cell Carcinomas

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This trial aims to directly compare a reduced radiation dose to the standard of care in
    HPVOPC for non-inferiority, thus allowing for direct comparison of outcomes between the two
    groups. The study hypothesis is that LRC and PFS at 3 years for reduced dose CRT are
    non-inferior to standard dose CRT.

    Detailed Description

    This is a randomized Phase III study comparing two doses of definitive radiation therapy
    given with induction and concurrent chemotherapy in HPV-positive oropharynx, unknown primary
    or nasopharynx cancer. Eligible, consented and registered patients will receive three cycles
    of Docetaxel Cisplatin and 5-FU (TPF) induction chemotherapy. After 3 cycles, the patients
    will be assessed for clinical, radiographic and pathologic response to TPF. Patients with a
    clinical or radiographic CR or PR will be randomized on the second phase of this study,
    where patients will undergo a 2:1 randomization to reduced (5600 cGy) or standard (7000 cGy)
    dose radiotherapy with weekly Carboplatin. Patients not meeting the response criteria will
    be treated with standard dose CRT. Patients not completing 3 cycles TPF for reasons of
    toxicity, progressive disease, choice, or other medical necessity will be treated with
    standard dose CRT or surgery depending on their primary site and overall medical condition
    and followed for survival. Toxicity will be assessed by Symptom scores, QOL and SAE
    monitoring. The primary end point of the trial is equivalent local regional control and PFS
    at 3 years. Patients will be followed for 5 years.

    Trial Arms

    Name Type Description Interventions
    Reduced Dose Radiation Experimental Patients randomized to receive a reduced (5600 cGy) dose radiotherapy with weekly Carboplatin
    Standard Dose Radiation Active Comparator Patients randomized to receive a standard (7000 cGy) dose radiotherapy with carboplatin

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must have histologically or cytologically confirmed squamous cell
    carcinoma of the oropharynx, unknown primary, or nasopharynx that is HPV positive as
    determined by PCR and p16 positive as determined by IHC. Tissue from the primary site
    must be available for biomarker studies. PCR and IHC must be performed in the central
    laboratory (Zhang, MSSM)

    - Stage 3 or 4 disease without evidence of distant metastases.

    - At least one clinically evaluable or uni- or bi-dimensionally measurable lesion by
    RECIST 1.1 criteria.

    - Age > 18 years.

    - No previous surgery, radiation therapy or chemotherapy for SSCHN (other than biopsy
    or tonsillectomy) is allowed at time of study entry.

    - ECOG performance status of 0 or 1.

    - No active alcohol addiction (as assessed by medical caregiver and defined as at least
    6 months without activity).

    - Participants must have adequate bone marrow, hepatic and renal functions as defined
    in the protocol.

    - Ability to understand and the willingness to sign a written informed consent
    document.

    - Patients with Gilbert's Disease and absent hepatic pathology by history and clinical
    assessment maybe treated on study with bilirubins > the ULN for the institution if
    other liver function studies are within the normal range

    Exclusion Criteria:

    - Pregnant or breast feeding women, or women and men of childbearing potential not
    willing to use adequate contraception while on treatment and for at least 3 months
    thereafter.

    - Previous or current malignancies at other sites, with the exception of adequately
    treated in situ carcinoma of the cervix, basal or squamous cell carcinoma of the
    skin, thyroid cancer, or other cancer curatively treated by surgery and with no
    current evidence of disease for at least 5 years.

    - Symptomatic peripheral neuropathy grade 2 by NCI Common Terminology Criteria
    (NCI-CTC) version 4.

    - Symptomatic altered hearing > grade 2 by NCI-CTCv4 criteria.

    - Other serious illnesses or medical conditions including but not limited to:

    1. Unstable cardiac disease despite treatment, myocardial infarction within 6
    months prior to study entry

    2. History of significant neurologic or psychiatric disorders including dementia or
    seizures

    3. Active clinically significant uncontrolled infection

    4. Active peptic ulcer disease defined as unhealed or clinically active

    5. Hypercalcemia

    6. Active drug addiction including alcohol, cocaine or intravenous drug use defined
    as occurring within the 6 months preceding diagnosis

    7. Chronic Obstructive Pulmonary Disease, defined as being associated with a
    hospitalization for pneumonia or respiratory decompensation within 12 months of
    diagnosis. This does not include obstruction from tumor

    8. Autoimmune disease requiring therapy, prior organ transplant, or HIV infection

    9. Interstitial lung disease

    10. Hepatitis C (test required)

    - Patients that have experienced an involuntary weight loss of more than 25% of their
    body weight in the 2 months preceding study entry.

    - Concurrent treatment with any other anticancer therapy.

    - Participation in an investigational therapeutic drug trial within 30 days of study
    entry.

    - Active smoking within the past 20 years with a cumulative Pack Year history of > 20
    Pack Years or active smoking (Defined as > 1 cigarette per day) within the last 2
    years

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival (PFS)

    Secondary Outcome Measures

    Rate of local-regional control

    Overall Survival

    Acute Toxicity of CRT

    Biomarkers predictive of failure

    Trial Keywords

    Reduced radiotherapy

    Randomization, Phase III

    Reduced radiation therapy

    head and neck

    oropharynx

    unknown primary (cervical lymph nodes)

    nasopharynx primary

    HPV

    p16