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

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ClinicalTrials.gov Identifier: NCT01706939
Recruitment Status : Active, not recruiting
First Posted : October 15, 2012
Last Update Posted : March 23, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinomas Radiation: Reduced Dose Radiation Radiation: Standard Dose Radiation Phase 3

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : September 2012
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021
Arms and Interventions

Arm Intervention/treatment
Experimental: Reduced Dose Radiation
Patients randomized to receive a reduced (5600 cGy) dose radiotherapy with weekly Carboplatin
Radiation: Reduced Dose Radiation
Reduced Dose Radiation (5600 cGy) dose radiotherapy with weekly Carboplatin
Active Comparator: Standard Dose Radiation
Patients randomized to receive a standard (7000 cGy) dose radiotherapy with carboplatin
Radiation: Standard Dose Radiation
Standard Dose Radiation (7000 cGy) dose radiotherapy with carboplatin

Outcome Measures

Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: at 3 years ]
    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 :
  1. Rate of local-regional control [ Time Frame: at 3 years ]
    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.

  2. Overall Survival [ Time Frame: at 5 years ]
    To determine Overall Survival (OS) 5 years treated with reduced or standard dose CRT.

  3. Acute Toxicity of CRT [ Time Frame: at 5 years ]
    To compare acute toxicity in patients treated with reduced or standard dose CRT.

  4. Biomarkers predictive of failure [ Time Frame: at 5 years ]
    To determine biomarkers predictive of failure with either reduced or standard dose radiotherapy.

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01706939

United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
The Biodesign Institute
Arizona State University
Principal Investigator: Marshall Posner, M.D. Icahn School of Medicine at Mount Sinai
More Information

Forastiere A, Maor M, Weber R, Pajak, T, Glisson B, Trotti A, Ridge J, et al. Long term results of Intergroup RTOG 91-11: A Phase III trial to preserve the larynx - Induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy. Proceedings of the American Society of Clinical Oncology. 2006:5517.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Marshall Posner, Director, Head and Neck Medical Oncology, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01706939     History of Changes
Other Study ID Numbers: GCO 12-1050
First Posted: October 15, 2012    Key Record Dates
Last Update Posted: March 23, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: randomized trial should not be shared until trial is over.

Keywords provided by Marshall Posner, Icahn School of Medicine at Mount Sinai:
Reduced radiotherapy
Randomization, Phase III
Reduced radiation therapy
head and neck
unknown primary (cervical lymph nodes)
nasopharynx primary

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Antineoplastic Agents