- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03323463
Major De-escalation to 30 Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma
A Prospective Single Arm Non-inferiority Trial of Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Human Papilloma Virus Associated Oropharyngeal Carcinoma (Major De-escalation to 30Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma)
The purpose of this study is to demonstrate that participants with HPV positive and hypoxia negative T1-2, N1-2c (AJCC, 7th ed.) oropharyngeal squamous cell carcinoma receiving a major de-escalated radiation therapy with 2 cycles of standard chemotherapy is not inferior to comparable subjects treated with the current standard chemoradiation.
Accrual for Cohort A has been completed.
Cohort B is active and continues to enroll participants where surgery is optional and proton is allowed.
Study Overview
Status
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Nadeem Riaz, MD
- Phone Number: 646-888-3495
- Email: RiazN@mskcc.org
Study Locations
-
-
Connecticut
-
Hartford, Connecticut, United States, 06102
- Hartford Healthcare (Data Collection)
-
-
Florida
-
Miami, Florida, United States, 33143
- Baptist Alliance MCI (Data Collection Only)
-
-
New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Memorial Sloan Kettering Basking Ridge
-
Middletown, New Jersey, United States, 07748
- Memorial Sloan Kettering Monmouth
-
Montvale, New Jersey, United States, 07645
- Memorial Sloan Kettering Bergen
-
-
New York
-
Commack, New York, United States, 11725
- Memorial Sloan Kettering Commack
-
Harrison, New York, United States, 10604
- Memorial Sloan Kettering Westchester
-
New York, New York, United States, 10021
- Memorial Sloan Kettering Cancer Center
-
Rockville Centre, New York, United States, 11570
- Memorial Sloan Kettering Rockville Centre
-
Uniondale, New York, United States, 11553
- Memorial Sloan Kettering Nassau
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Cohort A: Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls) from 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) and consent from the PI or co-PIs
- Cohort B: Pathologically (histologically or cytologically) proven diagnosis of HPV associated squamous cell carcinoma of the oropharynx (tonsil, base of tongue, or oropharyngeal walls). Surgical removal of primary site is no longer required.
Squamous cell carcinoma of the neck of unknown primary is allowed with excision biopsy of a lymph node (or core biopsy) and consent from the PI or co-PIs
- Subjects must have clinically or radiographically evident measurable disease at nodal stations.
- Clinical stage T1-2, N1-2c without evidence of distant metastasis based on FDG PET/CT.
Patients who have squamous cell carcinoma of the neck of unknown primary, and thus, are T0, are allowed with excision biopsy of a lymph node (or core biopsy) or consent from the PI or co-PI
- 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 Karnopsky Performance Status >/= 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)
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
- 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
Exclusion Criteria:
- Subjects with prior head and neck radiation therapy
- Subjects with simultaneous primary cancers outside of the oropharynx
- 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
- No particle therapy such as but not limited to proton therapy is allowed in Cohort A. For Cohort B, this exclusion is removed.
Severe, active co-morbidity defined as follows:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A: HPV associated oropharyngeal carcinoma
HPV associated oropharyngeal carcinoma subjects who also have no evidence of hypoxia.
This arm is closed to accrual.
|
All subjects on Cohort A and the first 100 subjects accrued to Cohort B will undergo a pre-treatment F-FMISO scan PET/CT scan pretreatment.
For both Cohort A and Cohort B, FMISO scan will be repeated between the 5th-10th RT day if pre-treatment scan is hypoxic.
If the repeat 18F-FMISOscan PET/CT demonstrates hypoxia, the subject will receive 70Gy concurrent with 2 cycles of chemotherapy.
All subjects accrued onto Cohort B after 100 accruals will undergo only one 18F-FMISO scan done 5-10 treatment days after start of radiation therapy.
Treatment will be delivered as one fraction per day on a standard 5 day per week schedule (excluding weekends and holidays), total of 30 Gy over 3 weeks at 2 Gy per fraction each day.
The gross nodes, the primary/postoperative bed if applicable, all subclinical areas at risk for disease will receive the same dose at 30Gy.
Cycle 1 (week 1): At the start of week 1 of IMRT, 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.
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).
Cycle 2 (Week 4): After the three weeks of radiation at week 4 when the subject no longer is receiving radiation therapy, subjects will receive cisplatin 100 mg/m2 intravenously.
The may be given for 2 consecutive days (50 mg/m2 each day for a total dose 100 mg/m2), typically on days 22 and 23, or as a single dose, typically on day 22.
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.
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).
|
Experimental: Arm B: HPV associated oropharyngeal carcinoma
HPV associated oropharyngeal carcinoma subjects who also have no evidence of hypoxia.
|
All subjects on Cohort A and the first 100 subjects accrued to Cohort B will undergo a pre-treatment F-FMISO scan PET/CT scan pretreatment.
For both Cohort A and Cohort B, FMISO scan will be repeated between the 5th-10th RT day if pre-treatment scan is hypoxic.
If the repeat 18F-FMISOscan PET/CT demonstrates hypoxia, the subject will receive 70Gy concurrent with 2 cycles of chemotherapy.
All subjects accrued onto Cohort B after 100 accruals will undergo only one 18F-FMISO scan done 5-10 treatment days after start of radiation therapy.
Treatment will be delivered as one fraction per day on a standard 5 day per week schedule (excluding weekends and holidays), total of 30 Gy over 3 weeks at 2 Gy per fraction each day.
The gross nodes, the primary/postoperative bed if applicable, all subclinical areas at risk for disease will receive the same dose at 30Gy.
Cycle 1 (week 1): At the start of week 1 of IMRT, 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.
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).
Cycle 2 (Week 4): After the three weeks of radiation at week 4 when the subject no longer is receiving radiation therapy, subjects will receive cisplatin 100 mg/m2 intravenously.
The may be given for 2 consecutive days (50 mg/m2 each day for a total dose 100 mg/m2), typically on days 22 and 23, or as a single dose, typically on day 22.
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.
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).
Proton beam using pencil beam delivery either with the Varian or IBA delivery systems will be allowed for Cohort B. Proton beam therapy will be given at the New York Proton Center in New York City, where MSKCC has a well-established business associate agreement and cooperative research agreement with, respectively.
If treatment at NYPC is not feasible, patients may be referred to ProCure in Somerset, NJ.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effectiveness of study treatment for participants receiving de-escalated radiation therapy radiation therapy, comparable to participants treated with the current standard of care chemoradiation by standard CT (or MRI) or tumor site and PET scan
Time Frame: 2 years (+/- 3 months)
|
The primary objective of this protocol is to demonstrate that the 2-year locoregional control for this cohort of subjects treated with a major de-escalated radiation dose of 30 Gy is not inferior to comparable subjects treated with the current standard chemoradiation at 70 GY by using a proportion test of patients who demonstrate 2-year locoregional control.
|
2 years (+/- 3 months)
|
Collaborators and Investigators
Investigators
- Principal Investigator: Nancy Lee, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Head and Neck Neoplasms
- Neoplasms, Squamous Cell
- Carcinoma
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Carboplatin
- Fluorouracil
Other Study ID Numbers
- 17-409
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HPV-Associated Oropharyngeal Squamous Cell Carcinoma
-
Jonathan Schoenfeld, MD, MPHNaverisRecruitingHPV Positive Oropharyngeal Squamous Cell Carcinoma | Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC... and other conditionsUnited States
-
Paul W. Read, MDTerminatedOropharyngeal Squamous Cell Carcinoma (OPSCCA) | HPV (Human Papillomavirus)-AssociatedUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingStage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 | Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma... and other conditionsUnited States
-
National Cancer Institute (NCI)NRG OncologySuspendedOropharyngeal Squamous Cell Carcinoma | Squamous Cell Carcinoma | Basaloid Squamous Cell Carcinoma | Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Papillary Squamous Cell Carcinoma | Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC... and other conditionsUnited States, Canada
-
Memorial Sloan Kettering Cancer CenterRecruitingOropharyngeal Cancer | HPV-Related Carcinoma | HPV Positive Oropharyngeal Squamous Cell CarcinomaUnited States
-
Jonsson Comprehensive Cancer CenterEli Lilly and CompanyTerminatedClinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Pathologic Stage IV HPV-Mediated (p16-Positive)... and other conditionsUnited States
-
TScan Therapeutics, Inc.RecruitingMelanoma | Cervical Cancer | Head and Neck Cancer | HPV-Related Malignancy | Ovarian Cancer | HPV-Related Carcinoma | HPV-Related Cervical Carcinoma | HPV Positive Oropharyngeal Squamous Cell Carcinoma | Non-small Cell Carcinoma | HPV - Anogenital Human Papilloma Virus Infection | HPV-Related Adenocarcinoma | HPV-Related Adenosquamous Carcinoma and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingHPV-Related Malignancy | Oropharynx Cancer | HPV-Related Carcinoma | HPV Positive Oropharyngeal Squamous Cell Carcinoma | HPVUnited States
-
Cue BiopharmaMerck Sharp & Dohme LLCActive, not recruitingHead and Neck Cancer | HPV-Related Carcinoma | HPV Positive Oropharyngeal Squamous Cell CarcinomaUnited States
-
Jonsson Comprehensive Cancer CenterAstraZenecaTerminatedOropharyngeal Squamous Cell Carcinoma | Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 | Pathologic... and other conditionsUnited States
Clinical Trials on F-FMISO PET/CT Scan
-
University of ArizonaBlue Earth Diagnostics; Banner University Medical CenterCompletedProstate AdenocarcinomaUnited States
-
Massachusetts General HospitalNational Cancer Institute (NCI)Completed
-
University of UtahRecruitingEsophageal CancerUnited States
-
University Hospital, BordeauxCompleted
-
Memorial Sloan Kettering Cancer CenterCompletedHead and Neck CancerUnited States
-
M.D. Anderson Cancer CenterWithdrawnHead and Neck Neoplasms | Metastases, Neoplasm | Squamous Cell CarcinomaUnited States
-
University of Texas Southwestern Medical CenterWithdrawn
-
Memorial Sloan Kettering Cancer CenterRecruitingHead and Neck Cancer | Head and Neck Neoplasms | Head and Neck Squamous Cell Carcinoma | Head and Neck CarcinomaUnited States
-
Fifth Affiliated Hospital, Sun Yat-Sen UniversityRecruitingThyroid Cancer | Lymph Node Metastases | Positron-Emission TomographyChina
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI); National Institutes of Health (NIH)Active, not recruitingNon-Small-Cell-Lung Cancer (NSCLC)United States