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The Quarterback Trial: A Randomized Phase III Clinical Trial Comparing Reduced and Standard Radiation Therapy Doses for Locally Advanced HPV16 Positive Oropharynx Cancer

Phase 3
18 Years
Open (Enrolling)
Squamous Cell Carcinomas

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Trial Information

The Quarterback Trial: A Randomized Phase III Clinical Trial Comparing Reduced and Standard Radiation Therapy Doses for Locally Advanced HPV16 Positive Oropharynx Cancer

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 and Erbitux or carboplatin only, respectively.
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.

Inclusion Criteria:

- Participants must have histologically or cytologically confirmed squamous cell
carcinoma of the oropharynx, unknown primary, or nasopharynx that is HPV 16 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

- 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

- 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

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival (PFS)

Outcome 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.

Outcome Time Frame:

at 3 years

Safety Issue:


Principal Investigator

Marshall Posner, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Icahn School of Medicine at Mount Sinai


United States: Institutional Review Board

Study ID:

GCO 12-1050



Start Date:

September 2012

Completion Date:

June 2021

Related Keywords:

  • Squamous Cell Carcinomas
  • Reduced radiotherapy
  • Randomization, Phase III
  • Reduced radiation therapy
  • head and neck
  • oropharynx
  • unknown primary (cervical lymph nodes)
  • nasopharynx primary
  • HPV16
  • p16
  • Carcinoma
  • Carcinoma, Squamous Cell



John Theurer Cancer Center at Hackensack University Medical CenterHackensack, New Jersey  07601
Icahn School of Medicine at Mount SinaiNew York, New York  10029