NCT03107182

Chemotherapy and Locoregional Therapy Trial (Surgery or Radiation) for Patients With Head and Neck Cancer

A Phase II Trial of Nivolumab/Nab-paclitaxel/Carboplatin Induction Chemotherapy Followed by Response-stratified Locoregional Therapy for Patients With Locoregionally Advanced HPV-related Oropharyngeal Cancer- the OPTIMA II Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Carboplatin, nab-paclitaxel, and nivolumab combination will be administered for three cycles of three weeks duration each. TORS or RT/CRT will be performed after induction chemotherapy (i.e. day 64 of therapy). Patients with low risk and small volume tonsillar disease (T1-T2, non-bulky N2A-N2B with ≤2 non-lower neck lymph nodes measuring ≤5 cm in size) or base of tongue disease (T1-2 with lateralized primary ≤3 cm, non-bulky N2A-N2B with ≤2 non-lower neck lymph nodes measuring ≤5 cm in size) who have ≥50% reduction by RECIST following induction chemotherapy will undergo TORS and selective nodal dissection. De-intensified adjuvant RT will be given for adverse pathologic features. Patients may refuse TORS treatment. Patients with low risk, who do not qualify for TORS (due to volume of disease or poor visualization/access) or refuse TORS, who have ≥50% reduction by RECIST following induction chemotherapy will be given de-intensified treatment with radiation alone to 50 Gy. Before induction chemotherapy, patients will undergo examination under anesthesia and direct laryngoscopy to tattoo and photograph the primary tumor to plan the post-induction resection. Adjuvant nivolumab will be offered to all patients for 6-months post completion of definitive therapy (7 doses given as a flat dose of 480mg, every four weeks).

Detailed description

A phase II trial in human papillomavirus (HPV)-positive oropharyngeal squamous cell cancer (as determined by p16 immunohistochemistry with confirmatory ISH or PCR) to determine radiologic response to induction chemotherapy with nivolumab. Patients will undergo evaluation by a multidisciplinary team prior to risk assessment. The patients will be assigned to high or low risk groups based on tumor size, lymph node involvement, and smoking history. Patients will be assigned to treatment with induction chemotherapy with carboplatin, nab-paclitaxel, and nivolumab. Radiologic response to induction chemotherapy according to RECIST measurement of tumor shrinkage will then be used for therapeutic stratification of locoregional therapy, consisting of either transoral robotic surgery (TORS) or radiation with or without chemotherapy. Patients with low risk disease (see table above) and small volume tonsillar/BOT disease (T1-2 primary, non-bulky N2A-N2B nodal status) who have ≥50% reduction by RECIST following induction chemotherapy will undergo TORS for primary site resection and selective nodal dissection as a definitive treatment if technically feasible with adjuvant radiation for adverse pathologic features. Patients with other low risk tumors e.g. with higher volume disease, or who refuse surgery, who also have ≥50% reduction by RECIST following induction chemotherapy will be given de-intensified treatment with radiation alone to 50 Gy (no chemotherapy). Patients with low risk features and \<50% but ≥30% reduction OR high risk features (T4, bulky N2B or N2C-N3, \>10 pack-years tobacco use) with ≥50% reduction will receive de-intensified chemoradiation with concurrent cisplatin-RT to 50 Gy (5 weeks) or TFHX to 45 Gy (3 cycles/6 weeks). Patients with low risk features and \<30% reduction OR high risk disease with \<50% reduction or any patients with progressive disease during induction chemotherapy will undergo chemoradiotherapy with concurrent cisplatin-RT to 70 Gy (7 weeks) or TFHX to 75 Gy (5 cycles/10 weeks). Patients with both high and low risk features who have ≥50% reduction will receive locoregional therapy targeting the pre-chemotherapy extent of disease only. Adjuvant nivolumab will be offered to all patients for 6-months post completion of definitive therapy (7 doses given as a flat dose of 480mg, every four weeks).

Conditions

• HPV-Related Squamous Cell Carcinoma
• HNSCC

Interventions

Type	Name	Description
DRUG	nab-paclitaxel	All enrolled patients will receive three 21-day cycles of nab-paclitaxel (100 mg/m2 on days 1, 8, 15; 9 doses total)
DRUG	Carboplatin	All enrolled patients will receive three 21-day cycles of carboplatin (AUC 6 on day 1; 3 doses total).
DRUG	Nivolumab	All enrolled patients will receive three 21-day cycles of nivolumab (360 mg on days 1; 3 doses total). Adjuvant nivolumab will be offered to all patients for 6-months post completion of locoregional therapy for a total of 7 doses.
DRUG	Cisplatin	Cisplatin will be given on an every 3 weeks basis at a dose of 100 mg/m2 IV over 3-4 hrs day 1 (or 2) and 22 (or 23). Only for patients on the Intermediate Dose Arm and additionally on day 43 (or 44) for patients on the Regular Dose Arm.
DRUG	Hydroxyurea	Patients on the Intermediate or Regular Dose Arms will receive chemoradiation for 3-5 cycles (6-10 weeks). On day 0 patients will start hydroxyurea at 500 mg PO q 12 hours x 6 days (11 doses). The first daily dose of hydroxyurea on days 1 - 5 is given 2 hours prior to the first fraction of daily radiotherapy.
DRUG	5-FU	Patients on the Intermediate or Regular Dose Arms will receive chemoradiation for 3-5 cycles (6-10 weeks). On day 0 at 1800 patients will start continuous infusion of 5-FU at 600 mg/m2/day x 5 days (120 hours).
DRUG	Dexamethasone	Patients on the Intermediate or Regular Dose Arms will receive chemoradiation for 3-5 cycles (6-10 weeks). On days 1-5 patients will receive dexamethasone 20 mg PO (IV) in am Day 1, 1 hr prior to paclitaxel
DRUG	Famotidine	Patients on the Intermediate or Regular Dose Arms will receive chemoradiation for 3-5 cycles (6-10 weeks). On days 1-5 patients will receive famotidine 20 mg PO (IV) in am Day 1, 1 hr prior to paclitaxel.
DRUG	Diphenhydramine	Patients on the Intermediate or Regular Dose Arms will receive chemoradiation for 3-5 cycles (6-10 weeks). On days 1-5 patients will receive diphenhydramine 50 mg PO (IV) in am Day 1, 30 mins prior to paclitaxel.
DRUG	Paclitaxel	Patients on the Intermediate or Regular Dose Arms will receive chemoradiation for 3-5 cycles (6-10 weeks). On days 1-5 patients will start paclitaxel 100 mg/m2 after first RT fraction on day 1 of each cycle. Paclitaxel should be administered in 250 ml 0.9% NaCl over 60 minutes.
PROCEDURE	Transoral robotic surgery (TORS)	Patients with low risk and small volume tonsillar disease (T1-T2, non-bulky N2A-N2B with ≤2 non-lower neck lymph nodes measuring ≤5 cm in size) or base of tongue disease (T1-2 with lateralized primary ≤3 cm, non-bulky N2A-N2B with ≤2 non-lower neck lymph nodes measuring ≤5 cm in size) who have ≥50% reduction by RECIST following induction chemotherapy will undergo TORS and selective nodal dissection. Patients may refuse TORS treatment. Patients will receive RT or TORS.
RADIATION	Adjuvant RT	Patients with low risk, who do not qualify for TORS (due to volume of disease or poor visualization/access) or refuse TORS, who have ≥50% reduction by RECIST following induction chemotherapy will be given de-intensified treatment with radiation alone to 50 Gy. Patients will receive RT or TORS.
RADIATION	Chemoradiotherapy	Patients who have low risk disease with \<50% but ≥30% reduction, or patients who have high risk disease and ≥50% reduction of tumor by RECIST with induction chemotherapy will receive CRT to 50 Gy with concurrent bolus cisplatin (x2 doses) or TFHX to 45 Gy (3 cycles). Patients who have low risk disease and \<30% reduction of tumor, patients who have high risk disease and \<50% reduction of tumor by RECIST, or any patient who has progressive disease with induction chemotherapy will receive CRT to 70 Gy with concurrent bolus cisplatin (x3 doses) or TFHX to 75 Gy (5 cycles).

Timeline

• Start date: 2017-06-27
• Primary completion: 2024-09-06
• Completion: 2024-09-06
• First posted: 2017-04-11
• Last updated: 2025-05-06
• Results posted: 2025-05-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study