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Squamous Cell CarcinomasPhase 3NCT01706939

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

A Phase 3 study testing Reduced Dose Radiation, Standard Dose Radiation and Carboplatin in people with Squamous Cell Carcinomas, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Carcinomas
What is being tested?
Reduced Dose Radiation, Standard Dose Radiation and Carboplatin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
1 siteUnited States
Study dates
1 Sep 2012to 1 May 2035
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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:
  • Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry
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  • History of significant neurologic or psychiatric disorders including dementia or seizures
  • Active clinically significant uncontrolled infection
  • Active peptic ulcer disease defined as unhealed or clinically active
  • Hypercalcemia
  • Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis
  • 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
  • Autoimmune disease requiring therapy, prior organ transplant, or HIV infection
  • Interstitial lung disease
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Reduced Dose Radiation, Standard Dose Radiation, Carboplatin
Keywords
Reduced radiotherapy, Randomization, Phase III, Reduced radiation therapy, head and neck, oropharynx, unknown primary (cervical lymph nodes), nasopharynx primary, HPV, p16
Medical subject headings
Carcinoma, Squamous Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Reduced Dose RadiationRadiation

    Reduced Dose Radiation (5600 cGy) dose radiotherapy

  • Standard Dose RadiationRadiation

    Standard Dose Radiation (7000 cGy) dose radiotherapy

  • CarboplatinDrug

    Day 1, every 7 days ( + 2 days)

Study groups in NCT01706939
Study groupRoleWhat they receive
Reduced Dose RadiationExperimentalPatients randomized to receive a reduced (5600 cGy) dose radiotherapy with weekly Carboplatin
Receives: Radiation: Reduced Dose Radiation; Drug: Carboplatin
Standard Dose RadiationActive comparatorPatients randomized to receive a standard (7000 cGy) dose radiotherapy with carboplatin
Receives: Radiation: Standard Dose Radiation; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Progression Free Survival (PFS)

    Progression free survival (PFS) at 5 years in patients with advanced HPV related oropharynx cancer, nasopharynx cancer or unknown primary treated with reduced or standard dose radiation.

    Measured: at 3 and 5 years

Secondary outcomes (9)

  1. Number of Participants With Local-regional Control

    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.

    Measured: at 3 years

  2. Number of Participants With Overall Survival at 5 Years

    Overall Survival (OS) 5 years treated with reduced or standard dose CRT.

    Measured: at 5 years

  3. Number of Participants With Acute Toxicity of Chemoradiotherapy (CRT)

    Number of participants with acute toxicity treated with reduced or standard dose CRT.

    Measured: at 5 years

  4. Biomarkers Predictive of Failure

    To determine biomarkers predictive of failure with either reduced or standard dose radiotherapy.

    Measured: at 5 years

  5. Overall Survival at 15 Years

    Measured: at 15 years

  6. Change in MD Anderson Dysphagia Inventory (MDADI) From Baseline

    MDADI is a questionnaire of 20 questions and contains a global subscale, and three other categories of questions (emotional, functional, and physical). The scores are summed and a mean score is calculated. This mean score was multiplied by 20 to obtain a score, with a range of 0 (extremely low functioning) to 100 (high functioning). Thus, a higher MDADI score represented better day-to-day functioning and better QOL.

    Measured: Baseline and 5 years

  7. Change in MD Anderson Symptom Inventory Symptom Inventory and Severity (MDASI-HN SI and SS)

    MD Anderson Symptom Inventory Symptom Inventory and Severity (MDASI-HN SI and SS) MDASI Head and Neck is a site-specific MDASI module which includes the core MDASI 13 symptom severity items (SS) and 6 symptom interference items (SI), alongside 9 items relevant to head and neck cancer. The scores are summed and a mean score is calculated on a scale of 0 (low severity or interference) to 10 (high severity or complete interference). In order to calculate the mean score, a majority of the subscale's items must have been completed.

    A lower or negative score reflects a better quality of life compared to baseline.

    Measured: Baseline and 5 years

  8. Change in Xerostomia Questionnaire (XQ)

    XQ is a nine questions survey developed specifically for xerostomia symptoms. The scores are summed and a mean score is calculated on a scale of 0 (low xerostomia interference) to 10 (high xerostomia interference). A lower or negative score reflects a better quality of life compared to baseline.

    Measured: Baseline and 5 years

  9. Change in European Organization for Research and Treatment of Cancer Questionnaire for Head and Neck (EORTC HN)

    The EORTC Head and Neck module was specifically designed and validated for head and neck cancer patients. This 35-item questionnaire contains 7 symptom scales (pain, swallowing, senses, speech, social eating, social contact, and sexuality), 6 single-item scales (difficulties of teeth, mouth opening, dry mouth, sticky saliva, coughing, and feeling ill), and 5 items about the additional use of pain medicine, nutritional supplements, and feeding tube and changes in body weight. All items were transformed to scales from 0 to 100, and divided into respective sub-scores of global health (GHS), functional (FS), and symptom scale (SS). Subscales from 0-100. A high score on global health and functional scale represents a better level of functioning, whereas a high score on a symptom scale and head and neck module indicates more severe symptoms.

    Measured: Baseline and 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2012 (estimated)
  2. Study start1 Sep 2012
  3. Primary completion1 Apr 2020
  4. Study completion1 May 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01706939
Sponsor's protocol ID
GCO 12-1050
Status last verified
Mar 2026
First submitted
14 Sep 2012
Last updated
9 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: randomized trial should not be shared until trial is over.

Publications

  • Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301. doi: 10.1200/JCO.2011.36.4596. Epub 2011 Oct 3.

    PubMed 21969503

  • Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008 Feb 1;26(4):612-9. doi: 10.1200/JCO.2007.14.1713.

    PubMed 18235120

  • Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, Ramqvist T, Lindholm J, Sparen P, Ye W, Dahlstrand H, Munck-Wikland E, Dalianis T. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer. 2009 Jul 15;125(2):362-6. doi: 10.1002/ijc.24339.

    PubMed 19330833

  • Andl T, Kahn T, Pfuhl A, Nicola T, Erber R, Conradt C, Klein W, Helbig M, Dietz A, Weidauer H, Bosch FX. Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control. Cancer Res. 1998 Jan 1;58(1):5-13.

    PubMed 9426048

  • Munger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, Grace M, Huh K. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004 Nov;78(21):11451-60. doi: 10.1128/JVI.78.21.11451-11460.2004. No abstract available.

    PubMed 15479788

  • Psyrri A, DeFilippis RA, Edwards AP, Yates KE, Manuelidis L, DiMaio D. Role of the retinoblastoma pathway in senescence triggered by repression of the human papillomavirus E7 protein in cervical carcinoma cells. Cancer Res. 2004 May 1;64(9):3079-86. doi: 10.1158/0008-5472.can-03-3739.

    PubMed 15126344

  • Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A. Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006 Feb 10;24(5):736-47. doi: 10.1200/JCO.2004.00.3335. Epub 2006 Jan 9.

    PubMed 16401683

  • Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.

    PubMed 20530316

  • Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000 May 3;92(9):709-20. doi: 10.1093/jnci/92.9.709.

    PubMed 10793107

  • Gillison ML. Human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma: implications for clinical research in head and neck cancers. J Clin Oncol. 2006 Dec 20;24(36):5623-5. doi: 10.1200/JCO.2006.07.1829. No abstract available.

    PubMed 17179099

  • Ringstrom E, Peters E, Hasegawa M, Posner M, Liu M, Kelsey KT. Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res. 2002 Oct;8(10):3187-92.

    PubMed 12374687

  • Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol. 2009 Apr 20;27(12):1992-8. doi: 10.1200/JCO.2008.20.2853. Epub 2009 Mar 16.

    PubMed 19289615

  • Licitra L, Perrone F, Bossi P, Suardi S, Mariani L, Artusi R, Oggionni M, Rossini C, Cantu G, Squadrelli M, Quattrone P, Locati LD, Bergamini C, Olmi P, Pierotti MA, Pilotti S. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol. 2006 Dec 20;24(36):5630-6. doi: 10.1200/JCO.2005.04.6136.

    PubMed 17179101

  • Cmelak AJ, Li S, Goldwasser MA, Murphy B, Cannon M, Pinto H, Rosenthal DI, Gillison M, Forastiere AA. Phase II trial of chemoradiation for organ preservation in resectable stage III or IV squamous cell carcinomas of the larynx or oropharynx: results of Eastern Cooperative Oncology Group Study E2399. J Clin Oncol. 2007 Sep 1;25(25):3971-7. doi: 10.1200/JCO.2007.10.8951.

    PubMed 17761982

  • Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, Forastiere A, Gillison ML. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008 Feb 20;100(4):261-9. doi: 10.1093/jnci/djn011. Epub 2008 Feb 12.

    PubMed 18270337

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Reduced Dose Radiation, Standard Dose Radiation and Carboplatin in people with Squamous Cell Carcinomas, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Progression Free Survival (PFS) (time frame: at 3 and 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01706939, which also lists 36 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.

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