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

Phase 2

Recruiting

Conditions: HPV
Oropharyngeal Carcinoma
Human Papilloma Virus
Oropharyngeal Cancer
Throat Cancer

Interventions: Diagnostic Test: 18 F-FMISO PET/CT
Radiation: Radiation
Drug: Cisplatin
Drug: Carboplatin
Drug: 5-fluorouracil

Registration Number: NCT05491512

Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 121

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort A	18 F-FMISO PET/CT	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)
Cohort A	Radiation	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)
Cohort B	18 F-FMISO PET/CT	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Participants in Cohort B will receive 1 cycle of carboplatin and Paclitaxol the same week of the start of radiation. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Paclitaxel can be substituted with Abraxane and the dose will be 50mg/m\^2. For Cohort B, patients over 70yrs will be able to enroll regardless of Cisplatin or carboplatin/5-fluorouracil (FU) eligibility.
Cohort B	Radiation	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Participants in Cohort B will receive 1 cycle of carboplatin and Paclitaxol the same week of the start of radiation. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Paclitaxel can be substituted with Abraxane and the dose will be 50mg/m\^2. For Cohort B, patients over 70yrs will be able to enroll regardless of Cisplatin or carboplatin/5-fluorouracil (FU) eligibility.
Cohort C	18 F-FMISO PET/CT	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). For participants in Cohort C where induction chemotherapy is used, additional pre-treatment 18F-FMISO PET and post induction pre radiation FMISO PET Scans will be obtained. These patients will start with induction chemotherapy of carboplatin, paclitaxel with or without cetuximab for 6 weeks and follow the same precision chemoradiation algorithm as Cohort A. A window of +/- 2 days is acceptable during the induction phase Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). For patients who cannot tolerate paclitaxel, Abraxane and the dose will be at 100mg/m\^2.
Cohort C	Radiation	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). For participants in Cohort C where induction chemotherapy is used, additional pre-treatment 18F-FMISO PET and post induction pre radiation FMISO PET Scans will be obtained. These patients will start with induction chemotherapy of carboplatin, paclitaxel with or without cetuximab for 6 weeks and follow the same precision chemoradiation algorithm as Cohort A. A window of +/- 2 days is acceptable during the induction phase Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). For patients who cannot tolerate paclitaxel, Abraxane and the dose will be at 100mg/m\^2.
Cohort D	18 F-FMISO PET/CT	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T1- T2N0 participants. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Will follow the guidelines for Cohort A and Cohort B for chemotherapy options.
Cohort D	Radiation	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T1- T2N0 participants. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Will follow the guidelines for Cohort A and Cohort B for chemotherapy options.
Cohort A	Cisplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)
Cohort B	Cisplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Participants in Cohort B will receive 1 cycle of carboplatin and Paclitaxol the same week of the start of radiation. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Paclitaxel can be substituted with Abraxane and the dose will be 50mg/m\^2. For Cohort B, patients over 70yrs will be able to enroll regardless of Cisplatin or carboplatin/5-fluorouracil (FU) eligibility.
Cohort A	Carboplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)
Cohort A	5-fluorouracil	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)
Cohort B	Carboplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Participants in Cohort B will receive 1 cycle of carboplatin and Paclitaxol the same week of the start of radiation. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Paclitaxel can be substituted with Abraxane and the dose will be 50mg/m\^2. For Cohort B, patients over 70yrs will be able to enroll regardless of Cisplatin or carboplatin/5-fluorouracil (FU) eligibility.
Cohort B	5-fluorouracil	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Participants in Cohort B will receive 1 cycle of carboplatin and Paclitaxol the same week of the start of radiation. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Paclitaxel can be substituted with Abraxane and the dose will be 50mg/m\^2. For Cohort B, patients over 70yrs will be able to enroll regardless of Cisplatin or carboplatin/5-fluorouracil (FU) eligibility.
Cohort C	Cisplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). For participants in Cohort C where induction chemotherapy is used, additional pre-treatment 18F-FMISO PET and post induction pre radiation FMISO PET Scans will be obtained. These patients will start with induction chemotherapy of carboplatin, paclitaxel with or without cetuximab for 6 weeks and follow the same precision chemoradiation algorithm as Cohort A. A window of +/- 2 days is acceptable during the induction phase Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). For patients who cannot tolerate paclitaxel, Abraxane and the dose will be at 100mg/m\^2.
Cohort C	Carboplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). For participants in Cohort C where induction chemotherapy is used, additional pre-treatment 18F-FMISO PET and post induction pre radiation FMISO PET Scans will be obtained. These patients will start with induction chemotherapy of carboplatin, paclitaxel with or without cetuximab for 6 weeks and follow the same precision chemoradiation algorithm as Cohort A. A window of +/- 2 days is acceptable during the induction phase Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). For patients who cannot tolerate paclitaxel, Abraxane and the dose will be at 100mg/m\^2.
Cohort C	5-fluorouracil	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). For participants in Cohort C where induction chemotherapy is used, additional pre-treatment 18F-FMISO PET and post induction pre radiation FMISO PET Scans will be obtained. These patients will start with induction chemotherapy of carboplatin, paclitaxel with or without cetuximab for 6 weeks and follow the same precision chemoradiation algorithm as Cohort A. A window of +/- 2 days is acceptable during the induction phase Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). For patients who cannot tolerate paclitaxel, Abraxane and the dose will be at 100mg/m\^2.
Cohort D	Cisplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T1- T2N0 participants. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Will follow the guidelines for Cohort A and Cohort B for chemotherapy options.
Cohort D	Carboplatin	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T1- T2N0 participants. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Will follow the guidelines for Cohort A and Cohort B for chemotherapy options.
Cohort D	5-fluorouracil	Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T1- T2N0 participants. Paclitaxel can be substituted with Abraxane (Albumin-bound Paclitaxel). Will follow the guidelines for Cohort A and Cohort B for chemotherapy options.

Primary Outcome Measures

Name	Time	Method
Number of participants with any locoregional recurrences	2 years	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (7): Memorial Sloan Kettering Bergen (Limited Protocol Activities)
🇺🇸
Montvale, New Jersey, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
🇺🇸
Middletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center at Basking Ridge (Limited Protocol Activities)
🇺🇸
Basking Ridge, 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, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
🇺🇸
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center at Suffolk-Commack (Limited Protocol Activities)
🇺🇸
Commack, New York, United States

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

Recruitment & Eligibility

Study & Design

Trial Locations

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