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

• ClinicalTrials.gov Identifier: NCT03323463
• Recruitment Status: Recruiting
• First Posted: October 27, 2017
• Last Update Posted: March 16, 2023
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: October 17, 2017
• First Posted Date: October 27, 2017
• Last Update Posted Date: March 16, 2023
• Actual Study Start Date: October 16, 2017
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 31, 2023)

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.

Original Primary Outcome Measures (submitted: October 23, 2017)

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) ]

Standard CT (or MRI) of tumor site and PET scan will be repeated at week 23 (+/-4 weeks) and 2 years (+/-3 months) after the completion of cycle 2 of chemotherapy infusion (week 4). MRI oropharynx includes both MRI Neck and MRI Oral Cavity/Tongue. CT Oropharynx is a CT Neck.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Major De-escalation to 30 Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma
• 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)

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• HPV-Associated Oropharyngeal Squamous Cell Carcinoma
• Squamous Cell Carcinoma of the Neck

Intervention

• 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.

Study Arms

• 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.
  Interventions:

  • Diagnostic Test: F-FMISO PET/CT Scan
  • Radiation: 30 Gy over 3 weeks
  • Drug: Cisplatin
  • Drug: Carboplatin
  • Drug: 5Fluorouracil
• Experimental: Arm B: HPV associated oropharyngeal carcinoma
  HPV associated oropharyngeal carcinoma subjects who also have no evidence of hypoxia.
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 6, 2020): 300
• Original Estimated Enrollment (submitted: October 23, 2017): 76
• Estimated Study Completion Date: October 31, 2024
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Nancy Lee, MD; 212-639-3341; leen2@mskcc.org

Contact: Nadeem Riaz, MD; 646-888-3495; RiazN@mskcc.org

• Listed Location Countries: United States
• Removed Location Countries: Canada

Administrative Information

• NCT Number: NCT03323463
• Other Study ID Numbers: 17-409
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nancy Lee, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: March 2023