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

NCT03107182 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB17-0104
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

HPV-Related Squamous Cell Carcinoma; HNSCC

Keywords

HPV- positive HNSCC; head and neck squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Evaluate the Tumor Shrinkage (%) to Measure the Deep Response Rate (DRR)

  DRR is defined as ≥50% tumor shrinkage by RECIST 1.1. We will evaluate the overall percentage of patients treated with dose-reduced radiotherapy or TORS to determine the tumor shrinkage based on treatment received.

  24 months

Secondary Outcomes (5)

• Number of Patients With Adverse Events

  24 months

• 2 Year Progression-free Survival (PFS)

  From start date of therapy to the date of first documented disease progression or death from any cause, whichever may come first, assessed up to 24 months

• 2 Year Overall Survival (OS)

  From start date of therapy to the date of documented death, assessed up to 24 months

• 2 Year Rates of Locoregional Control

  24 months

• 2 Year Rates of Distant Control

  24 months

Study Arms (4)

Induction Chemotherapy

EXPERIMENTAL

All enrolled patients will receive three 21-day cycles of chemotherapy consisting of nab-paclitaxel (100 mg/m2 on days 1, 8, 15; 9 doses total), carboplatin (AUC 5 on day 1; 3 doses total), and nivolumab (360 mg on days 1; 3 doses total). Growth factor support will be provided using G-CSF administered on days 16-18. Adjuvant nivolumab will be offered to all patients for 6-months post completion of locoregional therapy.

Drug: nab-paclitaxel; Drug: Carboplatin; Drug: Nivolumab

Single Modality De-escalation Arm (SDA)

EXPERIMENTAL

Following the induction treatments (carboplatin, nab-paclitaxel, and nivolumab), patients will be assessed based on response to chemotherapy and high or low risk status. 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 G.

Drug: Nivolumab; Procedure: Transoral robotic surgery (TORS); Radiation: Adjuvant RT

Intermediate De-escalation Arm (IDA)

EXPERIMENTAL

Following the induction treatments (carboplatin, nab-paclitaxel, and nivolumab), patients will be assessed based on response to chemotherapy and high or low risk status. Patients who have low risk disease with \<50% but ≥30% reduction of tumor by RECIST with induction chemotherapy will receive CRT to 50 Gy with concurrent bolus cisplatin (x2 doses) or TFHX (paclitaxel, 5-FU, hydroxyurea, dexamethasone, famotidine, and diphenhydramine) to 45 Gy (3 cycles). 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).

Drug: Nivolumab; Drug: Cisplatin; Drug: Hydroxyurea; Drug: 5-FU; Drug: Dexamethasone; Drug: Famotidine; Drug: Diphenhydramine; Drug: Paclitaxel; Radiation: Chemoradiotherapy

Regular Dose Arm (RDA)

EXPERIMENTAL

Following the induction treatments (carboplatin, nab-paclitaxel, and nivolumab), patients will be assessed based on response to chemotherapy and high or low risk status. Patients who have low risk disease and \<30% reduction of tumor by RECIST with induction chemotherapy will receive CRT to 70 Gy with concurrent bolus cisplatin (x3 doses) or TFHX (paclitaxel, 5-FU, hydroxyurea, dexamethasone, famotidine, and diphenhydramine) to 75 Gy (5 cycles). Patients who have high risk disease and \<50% reduction of tumor by RECIST with induction chemotherapy will receive CRT to 70 Gy with concurrent bolus cisplatin (x3 doses) or TFHX to 75 Gy (5 cycles). Any patient who has progressive disease will receive CRT to 70 Gy with concurrent bolus cisplatin (x3 doses) or TFHX to 75 Gy (5 cycles).

Drug: Nivolumab; Drug: Cisplatin; Drug: Hydroxyurea; Drug: 5-FU; Drug: Dexamethasone; Drug: Famotidine; Drug: Diphenhydramine; Drug: Paclitaxel; Radiation: Chemoradiotherapy

Interventions

nab-paclitaxel DRUG

All enrolled patients will receive three 21-day cycles of nab-paclitaxel (100 mg/m2 on days 1, 8, 15; 9 doses total)

Also known as: nanoparticle albumin-bound paclitaxel, Abraxane

Induction Chemotherapy

Carboplatin DRUG

All enrolled patients will receive three 21-day cycles of carboplatin (AUC 6 on day 1; 3 doses total).

Also known as: paraplatin

Induction Chemotherapy

Nivolumab DRUG

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.

Also known as: Opdivo

Induction Chemotherapy; Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA); Single Modality De-escalation Arm (SDA)

Cisplatin DRUG

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.

Also known as: platinol

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

Hydroxyurea DRUG

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.

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

5-FU DRUG

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).

Also known as: Adrucil, Carac

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

Dexamethasone DRUG

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

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

Famotidine DRUG

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.

Also known as: pepcid

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

Diphenhydramine DRUG

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.

Also known as: benadryl

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

Paclitaxel DRUG

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.

Also known as: taxol

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

Transoral robotic surgery (TORS) PROCEDURE

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.

Also known as: TORS

Single Modality De-escalation Arm (SDA)

Adjuvant RT RADIATION

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.

Also known as: RT

Single Modality De-escalation Arm (SDA)

Chemoradiotherapy RADIATION

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).

Also known as: CRT

Intermediate De-escalation Arm (IDA); Regular Dose Arm (RDA)

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically confirmed HPV-positive head and neck squamous cell carcinoma of the oropharynx. Confirmed HPV-positive disease of other subsites are uncommon but also eligible.
• HPV testing must be compliant with the following criteria:
• p16 IHC positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al89).
• p16 IHC positivity is to be validated using an HPV PCR during the induction phase. This is essential as HPV genotype influences treatment arm allocation, with non-HPV16 HPV strains being considered high risk.
• Availability of ≥10 unstained 5 micron slides (to be provided to HTRC at the University of Chicago). Patients who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
• Patients must be at least 18 years of age.
• Patients with AJCC (7th edition, 2010) N2-N3 nodal disease or T3-T4 primary tumor.
• Measurable disease (either primary site and/or nodal disease) by RECIST 1.1 criteria.
• No previous radiation or chemotherapy for a head and neck cancer.
• No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual disease is acceptable).
• ECOG performance status 0-1 (Karnofsky greater than or equal to 80%).
• Normal Organ Function
• Leukocytes ≥3000/mm3,
• platelets ≥100,000/mm3,
• absolute neutrophil count ≥1,500,

You may not qualify if:

• Unequivocal demonstration of distant metastases (M1 disease).
• Unidentifiable primary site.
• Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival. Including but not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance.
• Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment on study as outlined above
• Patients receiving other investigational agents.
• Peripheral neuropathy \>grade 1
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of physiologic dose or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active tuberculosis (Bacillus Tuberculosis infection)
• Has hypersensitivity to nivolumab or any other drug used in this protocol.
• Has had a prior systemic anti-cancer treatment within the last 8 weeks
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy).
• Has active autoimmune disease that has required systemic treatment in the past year (i.e. with use of steroids or immunosuppressive drugs). Replacement therapy e.g. levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). However, if eradicated patient is eligible.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Rosenberg AJ, Agrawal N, Juloori A, Cursio J, Gooi Z, Blair E, Chin J, Ginat D, Pasternak-Wise O, Hasina R, Starus A, Jones FS, Izumchenko E, MacCracken E, Wolk R, Cipriani N, Lingen MW, Pearson AT, Seiwert TY, Haraf DJ, Vokes EE. Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer: OPTIMA II Phase 2 Open-Label Nonrandomized Controlled Trial. JAMA Oncol. 2024 Jul 1;10(7):923-931. doi: 10.1001/jamaoncol.2024.1530.

  PMID: 38842838 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

130-nm albumin-bound paclitaxel; Taxes; Albumin-Bound Paclitaxel; Carboplatin; Nivolumab; Cisplatin; Hydroxyurea; Fluorouracil; Dexamethasone; Famotidine; Diphenhydramine; Paclitaxel; Chemoradiotherapy

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)

Economics; Health Care Economics and Organizations; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Urea; Amides; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Thiazoles; Sulfur Compounds; Azoles; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Results Point of Contact

• Title: Ari Rosenberg
• Organization: University of Chicago

arirosenberg@bsd.uchicago.edu

773-702-8222

Study Officials

• Everett Vokes, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 11, 2017
• Study Start: June 27, 2017
• Primary Completion: September 6, 2024
• Study Completion: September 6, 2024
• Last Updated: May 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Locations

US (1)