Major De-escalation to 30 Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03323463

Collaborator

(none)

300

Enrollment

Locations

Arms

84.5

Anticipated Duration (Months)

37.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HPV-Associated Oropharyngeal Squamous Cell Carcinoma Squamous Cell Carcinoma of the Neck	Diagnostic Test: F-FMISO PET/CT Scan Radiation: 30 Gy over 3 weeks Drug: Cisplatin Drug: Carboplatin Drug: 5Fluorouracil Radiation: Proton Therapy	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Oct 16, 2017

Anticipated Primary Completion Date :

Oct 31, 2024

Anticipated Study Completion Date :

Oct 31, 2024

Arms and Interventions

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.	Diagnostic Test: F-FMISO PET/CT Scan 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. Radiation: 30 Gy over 3 weeks 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. Drug: Cisplatin 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. Drug: 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). 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. Drug: 5Fluorouracil 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.	Diagnostic Test: F-FMISO PET/CT Scan 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. Radiation: 30 Gy over 3 weeks 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. Drug: Cisplatin 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. Drug: 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). 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. Drug: 5Fluorouracil 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). Radiation: Proton Therapy 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.

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.

Diagnostic Test: F-FMISO PET/CT Scan

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.

Radiation: 30 Gy over 3 weeks

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.

Drug: Cisplatin

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.

Drug: 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). 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.

Drug: 5Fluorouracil

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.

Diagnostic Test: F-FMISO PET/CT Scan

Radiation: 30 Gy over 3 weeks

Drug: Cisplatin

Drug: Carboplatin

Drug: 5Fluorouracil

Radiation: Proton Therapy

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.

Outcome Measures

Primary Outcome Measures

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 [2 years (+/- 3 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
7	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York	United States	11570
8	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553