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

NCT03323463 | Active Not Recruiting Phase 2 FDA Drug FDA Device

• 1 other identifier: 17-409
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 10

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.

Conditions

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

Keywords

squamous cell carcinoma of the neck of unknown primary; HPV-Associated Oropharyngeal Squamous Cell Carcinoma; Oropharyngeal Squamous Cell Carcinoma; 17-409; Hypoxia negative; N1-2c oropharyngeal squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  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)

Study Arms (2)

Arm A: HPV associated oropharyngeal carcinoma

EXPERIMENTAL

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; Radiation: 30 Gy over 3 weeks; Drug: Cisplatin; Drug: Carboplatin; Drug: 5Fluorouracil

Arm B: HPV associated oropharyngeal carcinoma

EXPERIMENTAL

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

Interventions

F-FMISO PET/CT Scan DIAGNOSTIC_TEST

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.

Arm A: HPV associated oropharyngeal carcinoma; Arm B: HPV associated oropharyngeal carcinoma

30 Gy over 3 weeks RADIATION

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.

Arm A: HPV associated oropharyngeal carcinoma; Arm B: HPV associated oropharyngeal carcinoma

Cisplatin DRUG

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.

Arm A: HPV associated oropharyngeal carcinoma; Arm B: HPV associated oropharyngeal carcinoma

Carboplatin DRUG

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.

Arm A: HPV associated oropharyngeal carcinoma; Arm B: HPV associated oropharyngeal carcinoma

5Fluorouracil DRUG

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).

Arm A: HPV associated oropharyngeal carcinoma; Arm B: HPV associated oropharyngeal carcinoma

Proton Therapy RADIATION

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 B: HPV associated oropharyngeal carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (10)

Hartford Healthcare (Data Collection)

Hartford, Connecticut, 06102, United States

Location

Baptist Alliance MCI (Data Collection Only)

Miami, Florida, 33143, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Lee NY, Sherman EJ, Schoder H, Wray R, Boyle JO, Singh B, Grkovski M, Paudyal R, Cunningham L, Zhang Z, Hatzoglou V, Katabi N, Diplas BH, Han J, Imber BS, Pham K, Yu Y, Zakeri K, McBride SM, Kang JJ, Tsai CJ, Chen LC, Gelblum DY, Shah JP, Ganly I, Cohen MA, Cracchiolo JR, Morris LGT, Dunn LA, Michel LS, Fetten JV, Kripani A, Pfister DG, Ho AL, Shukla-Dave A, Humm JL, Powell SN, Li BT, Reis-Filho JS, Diaz LA, Wong RJ, Riaz N. Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma. J Clin Oncol. 2024 Mar 10;42(8):940-950. doi: 10.1200/JCO.23.01308. Epub 2024 Jan 19.

  PMID: 38241600 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Carboplatin; Fluorouracil; Proton Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Study Officials

• Nancy Lee, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2017
• First Posted: October 27, 2017
• Study Start: October 16, 2017
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (10)