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Locally Advanced HPV Positive Oropharynx CancerNCT02945631

Quarterback 2b - Sequential Therapy With Reduced Dose Chemoradiotherapy for HPV Oropharynx Cancer

A study testing PTV56 and PTV50.4 in people with Locally Advanced HPV Positive Oropharynx Cancer, 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

The purpose of this study is to establish the efficacy and toxicity of low dose chemoradiotherapy after induction chemotherapy in patients with locally advanced HPV+ oropharynx cancer and establish prognostic factors that would apply to help select patients for this treatment in the future. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PTV56 and PTV50.4
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
25 Apr 2016to Dec 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

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 meet the following criteria to be eligible to participate in the study. Patients may enroll in the study if they meet all of the entry criteria, were candidates for induction chemotherapy regardless of HPV status and have to start therapy for logistic reasons prior to p16 and HPV testing. They will enter the experimental post-Induction portion of the study if the surgical specimens or biopsies are proven to be HPV+ on PCR testing. Patients who are HPV negative will be taken off study and treated with SOC radiotherapy and surgery:
  • Participants must have histologically or cytologically confirmed squamous cell carcinoma of the oropharynx, hypopharynx, supraglottic larynx, nasal cavity, unknown primary, or nasopharynx that is p16 and HPV positive. Tissue from the primary site or lymph node must be available for biomarker studies and for PCR testing. IHC must be performed in a lab verified by the central laboratory or the slides must be available for review by the central laboratory and PCR must be done in the central laboratory prior to radiotherapy. HPVPCR must be performed and results available for reduced dose therapy after induction.
  • Patients who are on the Quarterback Trial when Quarterback 2 is activated and who have been randomized to radiotherapy arm will be asked to transfer to this trial and receive the Quarterback 2 defined radiotherapy.
  • 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.
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  • 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 below:
  • - Hematology:
  • - Neutrophil count ≥ 1.5 x 10^9/l.
  • - Platelet count ≥ 100 x 10^9/l.
  • - Hemoglobin ≥ 10g/dl.
  • - Renal function ≥ 60 ml/min (actual or calculated by the Cockcroft-Gault method) as follows: CrCl (ml/min) = (140-age)(weight kg)/(mL/min) / 72 x serum creatinine (mg/dL)
  • - N.B. For females, use 85% of calculated CrCl value. Or a Creatinine ≤ the upper limits of normal
  • - Hepatic:
  • - Total Bilirubin ≤ institutional upper level of normal (ULN)
  • - AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility
  • Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment.
  • 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 may be treated on study with bilirubin > the ULN for the institution if other liver functions 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.These patients can be entered by substituting carboplatin for cisplatin with an AUC of 6.0
  • 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 by history, and confirmed by serology
  • 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 or a cumulative pack year history of > 20 pack years, active smoking is (Defined as ≥ 1 cigarette per day) within the last 5 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: Quarterback 22: A Phase II Clinical Trial of Sequential Therapy and De-Intensified Chemoradiotherapy for Locally Advanced HPV Positive Oropharynx Cancer

The purpose of this study is to establish the efficacy and toxicity of low dose chemoradiotherapy after induction chemotherapy in patients with locally advanced HPV+ oropharynx cancer and establish prognostic factors that would apply to help select patients for this treatment in the future.

Read the detailed description

In general, patients with Human Papilloma Virus Oropharynx Cancer (HPVOPC) are young and will live for prolonged periods. They are at high risk for long-term toxicity and mortality from radiotherapy. While the long-term consequences of chemotherapy for head and neck cancer are relatively constrained, high-dose radiotherapy (RT) and chemoradiotherapy (CRT) substantially impact on local tissues and organ function and result in a significant rate of late mortality and morbidity in patients. Studies are now being designed to reduce the impact of RT and CRT for patients. Identifying appropriate endpoints and study arms which will allow an early assessment of outcomes will be problematic, particularly for equivalence studies wherein survival differences are small, and where prolonged time periods and large patient numbers are necessary to accurately assess outcomes. For Sequential Therapy as given with TAX 324, 3-year PFS may be an appropriate endpoint. The same may not be possible for CRT. The best example of changing outcomes in CRT trials would be R91-11, in which a premature negative conclusion regarding the efficacy of induction therapy was published with the early analysis. Late toxicity and morbidity, a hallmark of upfront cisplatin-based CRT trials, led to equivalence between induction therapy and CRT for laryngectomy-free survival at 5 years, and more importantly a non-significant relative 10% improvement in overall survival in the PF induction arm compared to the CRT arm which included an every 3-week bolus cisplatin for 3 cycles during radiotherapy.

The survival results in HPVOPC achieved in TAX 324 and preliminary data from ECOG 1308 strongly suggest that it might be possible to reduce long-term morbidity in HPVOPC and preserve survival perhaps by better patient selection and by reducing radiotherapy intensity in the context of ST for more advanced cases. Best approach of HPV-negative disease might be with novel therapies and more aggressive Sequential Therapy (ST) or CRT.

Current radiation dose reduction trials are under way in ECOG, RTOG and other radiation based groups. The data from TAX 324 suggest that it is possible to reduce the radiation dose because of the superior progression free survival and the ability to select risk based CRT.

Being tested
PTV56, PTV50.4
Keywords
HPV, Induction Chemotherapy, De-Intensified Chemoradiotherapy, Oropharynx Cancer
Medical subject headings
Oropharyngeal Neoplasms

What participants receive

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

  • PTV56Radiation

    total dose of 56 Gy in 2.0 Gy/fraction x 28 fractions.

  • PTV50.4Radiation

    total dose of 50.4 Gy in 1.8 Gy /fraction x 28 fractions.

Study groups in NCT02945631
Study groupRoleWhat they receive
Reduced Dose RadiationExperimentalAll patients will receive daily radiation treatment with intensity-modulated radiotherapy (IMRT) - PTV56 and PTV50.4. Treatment will be given 5 days per week and will not routinely be delivered on Saturday, Sunday or major holidays unless a treatment is missed during the week due to technical and/or medical reasons. No more than 5 treatments should be given per week.
Receives: Radiation: PTV56; Radiation: PTV50.4

What is being measured

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

  1. Progression Free Survival (PFS)

    The comparative rate of progression free survival

    Measured: 3 years

  2. Progression Free Survival

    The comparative rate of progression free survival

    Measured: 5 years

Secondary outcomes (6)

  1. Local-regional control (LRC)

    The comparative rate of local-regional control

    Measured: 3 years

  2. Local-regional control (LRC)

    The comparative rate of local-regional control

    Measured: 5 years

  3. Overall Survival (OS)

    Measured: 3 years

  4. Overall Survival (OS)

    Measured: 5 years

  5. Acute Toxicity

    Rate of acute toxicity

    Measured: 5 years

  6. Long Term Toxicity

    Rate of long term toxicity

    Measured: 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 posted26 Oct 2016 (estimated)
  2. Study start25 Apr 2016
  3. Primary completionDec 2027 (estimated)
  4. Study completionDec 2027 (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 N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02945631
Sponsor's protocol ID
GCO 16-0609
Status last verified
Mar 2026
First submitted
25 Oct 2016
Last updated
2 Apr 2026
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

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 study testing PTV56 and PTV50.4 in people with Locally Advanced HPV Positive Oropharynx Cancer, 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 22 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 2 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Progression Free Survival (PFS) (time frame: 3 years). The study lists 2 primary outcomes in all. 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 NCT02945631, which also lists 35 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 2 Apr 2026.

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