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Human Papillomavirus (HPV)Phase 2NCT04849377

RBD-HPV: Risk-Based De-Intensification for HPV+ HNSCC

A Phase 2 study testing RT 50 Gy, RT 54 GY and RT 60 GY in people with Human Papillomavirus (HPV) and Head and Neck Squamous Cell Carcinoma (HNSCC), run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this research study is to determine the rate of local regional control at 2 years when using de-intensified chemoradiotherapy (CRT) in patients with Human Papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RT 50 Gy, RT 54 GY and RT 60 GY
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
14 Jun 2022to 14 Jun 2022
Phase
Phase 2
Are there results?
None posted in the registry

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

Inclusion Criteria: Patients must meet the following inclusion criteria to be eligible for enrollment in RBD-HPV:

  1. Histologically-confirmed squamous cell carcinoma of the head and neck, including subsites of the oropharynx, hypopharynx, larynx, and nasopharynx (with data on EBV)
  2. P16+ positivity as measured by IHC in a lab that is verified by the central laboratory or if the slides are available for review by the central laboratory
  3. HPV positivity by PCR assessed with either tissue or cytology in the central laboratory
  4. Stages I, II, III, or IV according to the AJCC 7th edition without evidence of distant metastases
  5. Age > 18
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  7. Adequate marrow function as defined by the following parameters:
  • Neutrophil count > 1.5 x 109/l
  • Platelet count > 100 x 109/l
  • Hemoglobin > 10 g/dl
  1. Adequate renal function as defined by a creatinine clearance > 60 ml/min (actual or calculated by the Cockcroft-Gault equation)
  2. Adequate liver function as defined by the following parameters:
  • Total bilirubin < institutional upper limit of normal (ULN) (except patients with Gilbert's Syndrome who have no other liver disease or abnormal liver serologies)
  • AST or ALT and alkaline phosphatase within the ranges described below
  1. A negative pregnancy test within 7 days of starting therapy in women of childbearing potential
  2. Capacity to understand the study protocol
  3. Willingness to provide written consent.

Exclusion Criteria: Patients will not be eligible for enrollment in this study if they exhibit any of the following conditions:

  1. Women who are currently pregnant or breast-feeding
  2. Men or women of childbearing potential who are not using adequate contraception during treatment and at least 3 months after therapy
  3. Current or prior malignancy in the last 5 years (excluding basal or squamous cell carcinoma of the skin not requiring systemic or radiation therapies, or prostate CA that is well-controlled and observed, etc)
  4. Radiation therapy for prior malignancy (except radioactive iodine for thyroid cancer)
  5. Prior chemotherapy for other malignancy or autoimmune disease
  6. Metastatic disease at presentation
  7. Nasal cavity subsite
  8. Active smoking (defined as > 1 cigarette per day within the last five years) or former smoking (has to have quit > 10 years ago) with a cumulative pack year history > 40 pack years
  9. Prior radiation therapy or chemotherapy for HNSCC (prior surgery alone is permitted)
  10. Active substance use disorder (ETOH or drugs, excluding marijuana)
  11. Prior use of IV drugs
  12. Significant peripheral neuropathy (> grade 2 according to NCI CTC)
  13. Prior hematologic or solid organ transplant
  14. Major medical comorbidity including:
  • Significant cardiovascular disease.
  • Significant neurologic disorder, including dementia and seizures.
  • Significant psychiatric disorder.
  • Active infection that is uncontrolled.
  • PUD (peptic ulcer disease) that is clinically active or unhealed.
  • Hypercalcemia.
  • COPD with hospitalization in the last 12 months for pneumonia or respiratory failure.
  • Interstitial lung disease.
  • Autoimmune disease requiring therapy.
  • Uncontrolled HIV infection (not on HAART, CD4 < 200).
  • Active Hepatitis C (+ RNA).
  1. Enrollment in a therapeutic clinical trial within 30 days of study entry
  2. Concurrent treatment with any other antineoplastic therapy
  3. Significant weight loss (> 25% of TBW) in the 2 months prior to study entry
  4. Patient has a history of non-adherence to medical care
  5. Patient will not be able to engage in comprehensive follow-up at Mount Sinai.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mount Sinai Hospital

    New York, New York, 10029

Other trials in United States

About this study

The purpose of this research study is to determine the rate of local regional control at 2 years when using de-intensified chemoradiotherapy (CRT) in patients with Human Papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). Local regional control means no recurrence of the cancer in the head or neck area. Study subjects will be enrolled into 4 groups. Group/treatment will be based on a number of factors, including smoking and drinking history.

Read the detailed description

The purpose of this research study is to determine the rate of local regional control at 2 years when using de-intensified chemoradiotherapy (CRT) in patients with Human Papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). Local regional control means no recurrence of the cancer in the head or neck area. Study subjects will be enrolled into 4 groups. Group/treatment will be based on a number of factors, including smoking and drinking history.

If participants choose to participate, participants will be asked to:

  • Participate in screening for eligibility, this will include: questions regarding \medical history, physical exam, blood/urine samples, electrocardiogram, PET/CT and/or CT-MRI of the neck, assessment of tumor, and a questionnaire.
  • Complete the study regimen including evaluations and follow up visits. Participants may be in this research study for approximately to 5 years after receiving standard of care (SOC) treatment. Depending on the group enrolled in, the treatment will last either 6 weeks (Groups 1-3) or 15 weeks (Group 4.This group will also receive 3 cycles of SOC induction therapy (One cycle = 21 days). Induction therapy is initial chemotherapy delivered prior to radiation or surgery when treating cancer.
  • Participate in routine types of procedures such as clinical exams, blood and urine tests, and imaging tests to assess tumor.
  • Consent to storage of research samples.

This research study involves chemotherapy and intensity-modulated radiation therapy (IMRT) IMRT is used to safely deliver precise radiation to a tumor while minimizing the dose to surrounding normal tissue.

There are no added costs associated with participation. There is no reimbursement for participation.

The names of the drugs/interventions involved in this study are:

  • Cisplatin
  • Docetaxel (Group 4 only)
  • Fluorouracil (Group 4 only)
  • Carboplatin (Group 4 Only)

All of the drugs listed above are approved for use by the Food and Drug Administration (FDA), commercially available, and considered standard of care (SOC) for cancer.

Serious known side effects that participants may experience include:

  • Nausea and vomiting
  • Diarrhea
  • Fever
  • Skin irritation, rash
  • Joint pain
Being tested
RT 50 Gy, RT 54 GY, RT 60 GY, Induction Therapy, Carboplatin
Keywords
Loco Regional Control (LRC), Risk-based De-intensified chemoradio therapy (CRT)
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

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

  • RT 50 GyRadiation

    Also called Radiation Therapy

    Radiation Therapy (RT) 50 GY

  • RT 54 GYRadiation

    Also called Radiation Therapy

    Radiation Therapy (RT) 54 GY

  • RT 60 GYRadiation

    Also called Radiation Therapy

    Radiation Therapy (RT) 60 GY

  • Induction TherapyOther

    Induction Therapy: Cisplatin, Docetaxel, Fluorouracil

  • CarboplatinDrug

    Carboplatin AUC 9.0

  • Cisplatin 200Drug

    200 mg/m2

  • Cisplatin 240Drug

    240mg/m2

Study groups in NCT04849377
Study groupRoleWhat they receive
Group I - 50 Gy/200 mg/m2ExperimentalPatient Characteristics: <20 Pack-Years, HPV16, OP, T1,T2 N0 RT 5 days per week for 6 weeks and Cisplatin weekly for 5 weeks
Receives: Radiation: RT 50 Gy; Drug: Cisplatin 200
Group II - 54 Gy/200mg/m2ExperimentalPatient Characteristics: <20 Pack-Years, HPV16, OP, T1-T2, N1-N2b, T3 N0-N2b RT 5 days per week for 6 weeks and Cisplatin weekly for 6 weeks
Receives: Radiation: RT 54 GY; Drug: Cisplatin 200
Group III - 60 Gy/240 mg/m2ExperimentalPatient Characteristics: 20-40 Pack-Years, Non-HPV16, Non-OP, T1-T2, N1-N2b, T3 N0-N2b RT 5 days per week for 6 weeks and Cisplatin weekly for 6 weeks
Receives: Radiation: RT 60 GY; Drug: Cisplatin 240
Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5ExperimentalPatient Characteristics: 20-40 Pack-Years, Non-HPV16, Non-OP, T4, N2c, >3 nodes, ENE, or Matted Nodes Induction Therapy: Cisplatin, Docetaxel, Fluorouracil followed by RT 60 GY + Carboplatin AUC 9.0 Docetaxel every 21 days for 3 cycles, Cisplatin every 21 days for 3 cycles, Fluorouracil continuous infusion over 4 days (every 21 days for 3 cycles). Followed by RT 5 days per week for 6 weeks and Carboplatin weekly for 6 weeks.
Receives: Radiation: RT 60 GY; Other: Induction Therapy; Drug: Carboplatin; Drug: Cisplatin 240

What is being measured

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

  1. Rate of Locoregional control (LRC)

    The rate of locoregional control (LRC) at 2 years - Local regional control means no recurrence of the cancer in the head or neck area.

    Measured: 2 years

Timeline

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

  1. First posted19 Apr 2021
  2. Study start14 Jun 2022
  3. Primary completion14 Jun 2022
  4. Study completion14 Jun 2022

Why it stopped: lack of eligible participants due to change in study criterias

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
CRT (Cisplatin with IMRT/IMPT): Group I 50 Gy/200 mg/m2, Group II 54 Gy/200 mg/m2, Group III 60 Gy/240 mg/m2 Sequential Therapy: Group IV TPF Induction followed by 60 Gy and Carboplatin AUC 1.5
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04849377
Sponsor's protocol ID
GCO 21-0525
Status last verified
Jul 2022
First submitted
14 Apr 2021
Last updated
7 Jul 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: All of the individual participant data collected during the trial, after deidentification.

Publications

  • D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56. doi: 10.1056/NEJMoa065497.

    PubMed 17494927

  • Carlander AF, Gronhoj Larsen C, Jensen DH, Garnaes E, Kiss K, Andersen L, Olsen CH, Franzmann M, Hogdall E, Kjaer SK, Norrild B, Specht L, Andersen E, van Overeem Hansen T, Nielsen FC, von Buchwald C. Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014. Eur J Cancer. 2017 Jan;70:75-82. doi: 10.1016/j.ejca.2016.10.015. Epub 2016 Nov 23.

    PubMed 27888679

  • Klussmann JP, Mooren JJ, Lehnen M, Claessen SM, Stenner M, Huebbers CU, Weissenborn SJ, Wedemeyer I, Preuss SF, Straetmans JM, Manni JJ, Hopman AH, Speel EJ. Genetic signatures of HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res. 2009 Mar 1;15(5):1779-86. doi: 10.1158/1078-0432.CCR-08-1463. Epub 2009 Feb 17.

    PubMed 19223504

  • Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, Moller B, Pukkala E, Schiller JT, Youngman L, Lehtinen M, Dillner J. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001 Apr 12;344(15):1125-31. doi: 10.1056/NEJM200104123441503.

    PubMed 11297703

  • Seiwert TY, Zuo Z, Keck MK, Khattri A, Pedamallu CS, Stricker T, Brown C, Pugh TJ, Stojanov P, Cho J, Lawrence MS, Getz G, Bragelmann J, DeBoer R, Weichselbaum RR, Langerman A, Portugal L, Blair E, Stenson K, Lingen MW, Cohen EE, Vokes EE, White KP, Hammerman PS. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res. 2015 Feb 1;21(3):632-41. doi: 10.1158/1078-0432.CCR-13-3310. Epub 2014 Jul 23.

    PubMed 25056374

  • Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S, Viscidi R. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008 Mar 19;100(6):407-20. doi: 10.1093/jnci/djn025. Epub 2008 Mar 11.

    PubMed 18334711

  • Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 Oct 10;33(29):3235-42. doi: 10.1200/JCO.2015.61.6995. Epub 2015 Sep 8.

    PubMed 26351338

  • Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010 Aug;11(8):781-9. doi: 10.1016/S1470-2045(10)70017-6. Epub 2010 May 5.

    PubMed 20451455

  • Dayyani F, Etzel CJ, Liu M, Ho CH, Lippman SM, Tsao AS. Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol. 2010 Jun 29;2:15. doi: 10.1186/1758-3284-2-15.

    PubMed 20587061

  • 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

  • Westra WH, Taube JM, Poeta ML, Begum S, Sidransky D, Koch WM. Inverse relationship between human papillomavirus-16 infection and disruptive p53 gene mutations in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2008 Jan 15;14(2):366-9. doi: 10.1158/1078-0432.CCR-07-1402.

    PubMed 18223210

  • 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

  • Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013 Dec 20;31(36):4550-9. doi: 10.1200/JCO.2013.50.3870. Epub 2013 Nov 18.

    PubMed 24248688

  • Braakhuis BJ, Snijders PJ, Keune WJ, Meijer CJ, Ruijter-Schippers HJ, Leemans CR, Brakenhoff RH. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. J Natl Cancer Inst. 2004 Jul 7;96(13):998-1006. doi: 10.1093/jnci/djh183.

    PubMed 15240783

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RT 50 Gy, RT 54 GY and RT 60 GY in people with Human Papillomavirus (HPV) and Head and Neck Squamous Cell Carcinoma (HNSCC), 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?

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: withdrawn, as of the sponsor's last update on 7 Jul 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Rate of Locoregional control (LRC) (time frame: 2 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 NCT04849377, which also lists 15 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 7 Jul 2022.

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