A Study of Reduced Radiation Therapy and Standard-of-Care Chemotherapy in People With HPV-Positive Throat Cancer

Human Papilloma Virus Clinical Trial

Official title:

Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Human Papilloma Virus Associated Oropharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05491512
• Other study ID #: 22-215
• Status: Recruiting
• Phase: Phase 2
• Start date: August 4, 2022
• Est. completion date: August 4, 2025

Study information

• Verified date: May 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Nancy Lee, MD
• Phone: 212-639-3341
• Email: leen2[@]MSKCC.ORG
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to find out if lower doses of radiation may help reduce the side effects of radiation therapy in combination with standard-of-care chemotherapy in people with HPV-positive throat cancer. The chemotherapy drugs used in this study include cisplatin, carboplatin, and 5-fluorouracil (5- FU), paclitaxel and abraxane- (Albumin-bound Paclitaxel).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 121
• Est. completion date: August 4, 2025
• Est. primary completion date: August 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from biopsy, surgical resection or excisional biopsy regardless of margin status.

1. Squamous cell carcinoma of the neck of unknown primary is allowed with excision biopsy of a lymph node (or core biopsy) or consent from the PI or co-PI

2. Patient must have excisional biopsy or core biopsy done in order to be on protocol

• Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations.
• Oropharyngeal Carcinoma (AJCC, 7th ed.) without evidence of distant metastasis based on FDG PET/CT.
• CT or MRI of the neck with and without contrast Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning may serve as planning tools.
• ECOG Performance Status of 0-2 or KPS = 50
• Age = 18 Patients over 70yrs will be able to enroll in Cohort B only).
• Adequate hematologic function within 30 days prior to registration, defined as

follows:

1. White Blood Count (WBC) = 2 K/mcL

2. Absolute neutrophil count (ANC) = 1,000 cells/mm3

3. Platelets = 100,000 cells/mm3

4. Hemoglobin = 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb = 8.0 g/dl is acceptable

• Adequate renal function within 30 days prior to registration, defined as follows:

1. Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) = 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male) Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel).

• Adequate hepatic function within 30 days prior to registration, defined as follows:

1. Bilirubin < 2 mg/dl

2. AST or ALT < 3 x the upper limit of normal Note: Exceptions can be made with PI and/or Co-Pi approval for patients to enroll on trial with a higher Bilirubin level such as Gilbert's Syndrome. Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and paclitaxel. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel).

• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
• The subject must provide study-specific informed consent prior to study entry
• Subject able to undergo MRI scans except for major medical contraindications like presence of a pacemaker or approved by the PI or the CO-PI that the subject does not need to undergo MRI scans

Exclusion Criteria:

• Subjects with prior head and neck radiation therapy
• Subjects with simultaneous primary cancers outside of the oropharynx a. Note: Exceptions can be made for patients with simultaneous primaries outside the oropharynx if determined by the PI/Co-PI the patient can proceed with protocol activities.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years to be 90% or greater
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
• Severe, active co-morbidity defined as follows: (exceptions can be made if approved by the PI and/or co-PI)

1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months

2. Transmural myocardial infarction within the last 6 months

3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

4. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration

5. Hepatic Insufficiency resulting in clinical jaundice and/or coagulation defects

Related Conditions & MeSH terms

• Carcinoma
• HPV
• Human Papilloma Virus
• Oropharyngeal Cancer
• Oropharyngeal Carcinoma
• Oropharyngeal Neoplasms
• Papilloma
• Throat Cancer

Intervention

Diagnostic Test:
• 18 F-FMISO PET/CT
The 18F-FMISO PET/CT Scan Protocol consists first of an IV bolus injection of approximately 5-10 mCi of the radiotracer. At between 150-180 mins post injection, 18F-FMISO images will be acquired.

Radiation:
• Radiation
Total Radiation Dose (over 3 weeks) 30Gy** in 2 Gy per fraction

Drug:
• Cisplatin
Concurrent chemotherapy (2 cycles) will be given. At the start of week 1 of radiation, subjects will receive cisplatin 100 mg/m2 intravenously. They may be given for 2 consecutive days (50 mg/m2 each day for a total dose 100 mg/m2 ), typically on days 1 and 2, or as a single dose, typically on day 1.
• Carboplatin
If cisplatin cannot be given at 100 mg/m2 for either cycle 1 or cycle 2, the investigator may use a regimen with carboplatin and 5-Fluorouracil in its place. Carboplatin will be given at a dose of AUC 1.25 intravenously daily x 4 days starting on day 1 of the cycle (total dose of AUC 5). 5-Fluorouracil will be given at a dose of 600 mg/m2 intravenous infusion over 24 hours daily x 4 days (total dose of 2400 mg/m2 intravenous infusion over 96 hours). (Cohort B to start carboplatin (AUC 1.5) and paclitaxel 45 mg/m2 at the start of RT)
• 5-fluorouracil
If cisplatin cannot be given at 100 mg/m2 for either cycle 1 or cycle 2, the investigator may use a regimen with carboplatin and 5-Fluorouracil in its place. Carboplatin will be given at a dose of AUC 1.25 intravenously daily x 4 days starting on day 1 of the cycle (total dose of AUC 5). 5-Fluorouracil will be given at a dose of 600 mg/m2 intravenous infusion over 24 hours daily x 4 days (total dose of 2400 mg/m2 intravenous infusion over 96 hours).

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center at Suffolk-Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with any locoregional recurrences	The primary objective of this protocol is to demonstrate that the 2 year locoregional control for these subjects treated with a major de-escalated radiation dose of 30Gy is acceptable as compared to historical locoregional control rate for subjects treated with the current standard chemoradiation at 70Gy. To examine if subjects receiving 30Gy have an acceptable treatment outcome when compared to the radiation of 70Gy both in the setting of concurrent chemotherapy, we will test the hypothesis that H0: P<=85% vs H1: P>85%, where P represents the 2-year locoregional control rate.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center