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

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

  • ORG STUDY ID: GCO 12-1050
  • NCT ID: NCT01706939

Conditions

  • Squamous Cell Carcinomas

Interventions

DrugSynonymsArms
CarboplatinReduced Dose Radiation

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

NameTypeDescriptionInterventions
Reduced Dose RadiationExperimentalPatients randomized to receive a reduced (5600 cGy) dose radiotherapy with weekly Carboplatin
  • Carboplatin
Standard Dose RadiationActive ComparatorPatients randomized to receive a standard (7000 cGy) dose radiotherapy with carboplatin
  • 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:at 3 years
Safety Issue:
Description:To determine the comparative rate of progression free survival (PFS) at 3 years in patients with advanced HPV related oropharynx cancer, nasopharynx cancer or unknown primary treated with reduced or standard dose radiation.

Secondary Outcome Measures

Measure:Rate of local-regional control
Time Frame:at 3 years
Safety Issue:
Description:To determine the comparative rate of local-regional control (LRC) at 3 years in patients with advanced HPV related oropharynx cancer or unknown primary treated with reduced or standard dose radiation.
Measure:Overall Survival
Time Frame:at 5 years
Safety Issue:
Description:To determine Overall Survival (OS) 5 years treated with reduced or standard dose CRT.
Measure:Acute Toxicity of CRT
Time Frame:at 5 years
Safety Issue:
Description:To compare acute toxicity in patients treated with reduced or standard dose CRT.
Measure:Biomarkers predictive of failure
Time Frame:at 5 years
Safety Issue:
Description:To determine biomarkers predictive of failure with either reduced or standard dose radiotherapy.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Icahn School of Medicine at Mount Sinai

Trial Keywords

  • Reduced radiotherapy
  • Randomization, Phase III
  • Reduced radiation therapy
  • head and neck
  • oropharynx
  • unknown primary (cervical lymph nodes)
  • nasopharynx primary
  • HPV
  • p16

Last Updated

January 28, 2021