search
Back to results

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

Primary Purpose

HPV, Throat Cancer, Oropharyngeal Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
18 F-FMISO PET/CT
Radiation
Cisplatin
Carboplatin
5-fluorouracil
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HPV focused on measuring HPV-Positive Throat Cancer, HPV, Throat Cancer, Human Papilloma Virus, Oropharyngeal Carcinoma, Oropharyngeal Cancer, Radiation Therapy, 22-215, Memorial Sloan Kettering Cancer Center

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

    a. 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

  • Subjects must have clinically or radiographically evident measurable gross disease at either the primary tumor site or nodal stations.
  • Clinical stage T1-3/N1-2c, T2-3/N0-2c, T0/N1-N2c (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
  • 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:

    a. 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)

  • 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
  • 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:

    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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center at Basking Ridge (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center at Suffolk-Commack (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)Recruiting
  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)Recruiting
  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort A

Cohort B

Cohort C

Cohort D

Arm Description

Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)

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 one week prior to the start of 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.

Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T2N0 participants.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
August 4, 2022
Last Updated
March 21, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
search

1. Study Identification

Unique Protocol Identification Number
NCT05491512
Brief Title
A Study of Reduced Radiation Therapy and Standard-of-Care Chemotherapy in People With HPV-Positive Throat Cancer
Official Title
Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Human Papilloma Virus Associated Oropharyngeal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 4, 2022 (Actual)
Primary Completion Date
August 4, 2024 (Anticipated)
Study Completion Date
August 4, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HPV, Throat Cancer, Oropharyngeal Carcinoma, Oropharyngeal Cancer, Human Papilloma Virus
Keywords
HPV-Positive Throat Cancer, HPV, Throat Cancer, Human Papilloma Virus, Oropharyngeal Carcinoma, Oropharyngeal Cancer, Radiation Therapy, 22-215, Memorial Sloan Kettering Cancer Center

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
121 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A
Arm Type
Experimental
Arm Description
Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC)
Arm Title
Cohort B
Arm Type
Experimental
Arm Description
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 one week prior to the start of radiation
Arm Title
Cohort C
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort D
Arm Type
Experimental
Arm Description
Participants diagnosed with hypoxia negative human papilloma virus (HPV) associated oropharyngeal carcinoma (OPC). Cohort D will just have T2N0 participants.
Intervention Type
Diagnostic Test
Intervention Name(s)
18 F-FMISO PET/CT
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Description
Total Radiation Dose (over 3 weeks) 30Gy** in 2 Gy per fraction
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of participants with any locoregional recurrences
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. 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 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 Adequate hematologic function within 30 days prior to registration, defined as follows: White Blood Count (WBC) ≥ 2 K/mcL Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 Platelets ≥ 100,000 cells/mm3 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: 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 Adequate hepatic function within 30 days prior to registration, defined as follows: Bilirubin < 2 mg/dl AST or ALT < 3 x the upper limit of normal Note: Patients who cannot tolerate cisplatin or carboplatin/5FU based on clinical judgment will receive carboplatin and 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) Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months Transmural myocardial infarction within the last 6 months Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration Hepatic Insufficiency resulting in clinical jaundice and/or coagulation defects
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nancy Lee, MD
Phone
212-639-3341
Email
leen2@MSKCC.ORG
First Name & Middle Initial & Last Name or Official Title & Degree
Heiko Schoder, MD
Phone
212-639-2079
Email
schoderh@MSKCC.ORG
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center at Basking Ridge (Limited Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Phone
212-639-3341
Facility Name
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Phone
212-639-3341
Facility Name
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Phone
212-639-3341
Facility Name
Memorial Sloan Kettering Cancer Center at Suffolk-Commack (Limited Protocol Activities)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Phone
212-639-3341
Facility Name
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Phone
212-639-3341
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Phone
212-639-3341
Facility Name
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Phone
212-639-3341

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

We'll reach out to this number within 24 hrs