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

July 1, 2022 updated by: Marshall Posner, MD, Icahn School of Medicine at Mount Sinai
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Mount Sinai Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  8. Adequate renal function as defined by a creatinine clearance > 60 ml/min (actual or calculated by the Cockcroft-Gault equation)

  9. 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
  10. A negative pregnancy test within 7 days of starting therapy in women of childbearing potential
  11. Capacity to understand the study protocol
  12. 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).
  15. Enrollment in a therapeutic clinical trial within 30 days of study entry
  16. Concurrent treatment with any other antineoplastic therapy
  17. Significant weight loss (> 25% of TBW) in the 2 months prior to study entry
  18. Patient has a history of non-adherence to medical care
  19. Patient will not be able to engage in comprehensive follow-up at Mount Sinai.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group I - 50 Gy/200 mg/m2
Patient Characteristics: <20 Pack-Years, HPV16, OP, T1,T2 N0 RT 5 days per week for 6 weeks and Cisplatin weekly for 5 weeks
Radiation: RT 50 Gy
Radiation Therapy (RT) 50 GY
Other Names:
  • Radiation Therapy
Drug: Cisplatin 200
200 mg/m2
Experimental: Group II - 54 Gy/200mg/m2
Patient 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
Drug: Cisplatin 200
200 mg/m2
Radiation: RT 54 GY
Radiation Therapy (RT) 54 GY
Other Names:
  • Radiation Therapy
Experimental: Group III - 60 Gy/240 mg/m2
Patient 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
Radiation: RT 60 GY
Radiation Therapy (RT) 60 GY
Other Names:
  • Radiation Therapy
Drug: Cisplatin 240
240mg/m2
Experimental: Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5
Patient 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.
Radiation: RT 60 GY
Radiation Therapy (RT) 60 GY
Other Names:
  • Radiation Therapy
Drug: Cisplatin 240
240mg/m2
Other: Induction Therapy
Induction Therapy: Cisplatin, Docetaxel, Fluorouracil
Drug: Carboplatin
Carboplatin AUC 9.0

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of Locoregional control (LRC)
Time Frame: 2 years
The rate of locoregional control (LRC) at 2 years - Local regional control means no recurrence of the cancer in the head or neck area.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Investigators

  • Principal Investigator: Marshall Posner, MD, Ichan School of Medicine at Mount Sinai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 14, 2022

Primary Completion (Actual)

June 14, 2022

Study Completion (Actual)

June 14, 2022

Study Registration Dates

First Submitted

April 14, 2021

First Submitted That Met QC Criteria

April 14, 2021

First Posted (Actual)

April 19, 2021

Study Record Updates

Last Update Posted (Actual)

July 7, 2022

Last Update Submitted That Met QC Criteria

July 1, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 21-0525

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

All of the individual participant data collected during the trial, after deidentification.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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