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.
Not yet recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Carboplatin | Group IV - TPF Induction followed by 60 Gy and Carboplatin AUC 1.5 | |
| Cisplatin 200 | Group I - 50 Gy/200 mg/m2 | |
| Cisplatin 240 | Group III - 60 Gy/240 mg/m2 |
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, they 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
| Name | Type | Description | Interventions |
|---|---|---|---|
| Group I - 50 Gy/200 mg/m2 | Experimental | 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 | Experimental | 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 | Experimental | 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 | Experimental | 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. |
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Rate of Locoregional control (LRC) |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | The rate of locoregional control (LRC) at 2 years - Local regional control means no recurrence of the cancer in the head or neck area. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Icahn School of Medicine at Mount Sinai |
April 19, 2021
