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

Phase 2

Withdrawn

• Conditions: Human Papillomavirus (HPV); Head and Neck Squamous Cell Carcinoma (HNSCC)
• Interventions: Radiation: RT 50 Gy; Radiation: RT 54 GY; Radiation: RT 60 GY; Drug: Cisplatin 200; Other: Induction Therapy; Drug: Carboplatin; Drug: Cisplatin 240

• Registration Number: NCT04849377
• Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief 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). 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.

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 Timeline

• Study First Submitted: 2021-04-14
• Study First Submitted QC: 2021-04-14
• Study First Posted: 2021-04-19
• Study Start: 2022-06-14
• Primary Completion: 2022-06-14
• Study Completion: 2022-06-14
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-01
• Last Update Posted: 2022-07-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Group II - 54 Gy/200mg/m2	Cisplatin 200	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
Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5	Cisplatin 240	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.
Group I - 50 Gy/200 mg/m2	RT 50 Gy	Patient Characteristics: \<20 Pack-Years, HPV16, OP, T1,T2 N0 RT 5 days per week for 6 weeks and Cisplatin weekly for 5 weeks
Group I - 50 Gy/200 mg/m2	Cisplatin 200	Patient Characteristics: \<20 Pack-Years, HPV16, OP, T1,T2 N0 RT 5 days per week for 6 weeks and Cisplatin weekly for 5 weeks
Group II - 54 Gy/200mg/m2	RT 54 GY	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
Group III - 60 Gy/240 mg/m2	RT 60 GY	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
Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5	Induction Therapy	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.
Group III - 60 Gy/240 mg/m2	Cisplatin 240	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
Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5	RT 60 GY	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.
Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5	Carboplatin	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.

Primary Outcome Measures

Name	Time	Method
Rate of Locoregional control (LRC)	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.

Trial Locations

Locations (1)

Mount Sinai Hospital; 🇺🇸 New York, New York, United States