The Quarterback Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Mount Sinai School of Medicine
Sponsor:
Collaborators:
The Biodesign Institute
Arizona State University
Information provided by (Responsible Party):
Marshall Posner, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01706939
First received: September 14, 2012
Last updated: February 10, 2014
Last verified: February 2014
  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.


Condition Intervention Phase
Squamous Cell Carcinomas
Radiation: Reduced Dose Radiation
Radiation: Standard Dose Radiation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Quarterback Trial: A Randomized Phase III Clinical Trial Comparing Reduced and Standard Radiation Therapy Doses for Locally Advanced HPV16 Positive Oropharynx Cancer

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
    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:
  • Rate of local-regional control [ Time Frame: at 3 years ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: at 5 years ] [ Designated as safety issue: Yes ]
    To determine Overall Survival (OS) 5 years treated with reduced or standard dose CRT.

  • Acute Toxicity of CRT [ Time Frame: at 5 years ] [ Designated as safety issue: Yes ]
    To compare acute toxicity in patients treated with reduced or standard dose CRT.

  • Biomarkers predictive of failure [ Time Frame: at 5 years ] [ Designated as safety issue: Yes ]
    To determine biomarkers predictive of failure with either reduced or standard dose radiotherapy.


Estimated Enrollment: 365
Study Start Date: September 2012
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01706939

Contacts
Contact: Nadia Camille (212) 241-5253 nadia.camille@mountsinai.org
Contact: Sanobar Parkar (212) 824-7403 sanobar.parkar@mssm.edu

Locations
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Jane Haynes    551-996-8018    jhayes@hackensackumc.org   
Principal Investigator: Robert Alter, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Marshall Posner, MD       marshall.posner@mssm.edu   
Contact: Krzysztof Misiukiewicz, MD       krzysztof.misiukiewicz@mssm.edu   
Principal Investigator: Marshall Posner, MD         
Sponsors and Collaborators
Mount Sinai School of Medicine
The Biodesign Institute
Arizona State University
Investigators
Principal Investigator: Marshall Posner, M.D. Mount Sinai School of Medicine
  More Information

Publications:

Responsible Party: Marshall Posner, Director, Head and Neck Medical Oncology, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01706939     History of Changes
Other Study ID Numbers: GCO 12-1050, HS 12-00359, IF 1403412
Study First Received: September 14, 2012
Last Updated: February 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Reduced radiotherapy
Randomization, Phase III
Reduced radiation therapy
head and neck
oropharynx
unknown primary (cervical lymph nodes)
nasopharynx primary
HPV
p16

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 29, 2014