Nab-Paclitaxel, Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer

A Phase II Multi-Center Study of Concomitant Cetuximab and Cisplatin With Re-Irradiation Using Intensity-Modulated Radiotherapy in Patients With Recurrent Squamous Cell Carcinoma of the Head-and-Neck

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab and cisplatin together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab and cisplatin together with radiation therapy works in treating patients with recurrent head and neck cancer.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: cetuximab; Drug: cisplatin; Radiation: intensity-modulated radiation therapy; Drug: Nab-Paclitaxel

Detailed Description

OBJECTIVES:

Primary

• To evaluate whether treatment with cetuximab, cisplatin, and intensity-modulated radiotherapy improves the overall survival of patients with recurrent squamous cell carcinoma of the head and neck.

Secondary

• To determine the progression-free survival and local-regional progression in these patients.
• To identify and estimate the incidence rate of acute and late toxicities associated with this treatment regimen.
• To determine the pattern of disease progression in these patients.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 60-120 minutes once weekly in weeks 1-7. Patients also receive cisplatin IV over 60 minutes once weekly and undergo intensity-modulated radiotherapy once daily 5 days a week in weeks 2-7.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 4 years.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
  • Texas
    • Dallas, Texas, United States, 75204
      • Baylor Research Institute
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center - Dallas
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Pathologically confirmed squamous cell carcinoma (SCC) of the upper aerodigestive tract

• Recurrent disease or second primary SCC

  • Recurrence or second primary must be confined to the head and neck above the clavicles (loco-regional recurrence)
  • Majority (≥ 75%) of the recurrent tumor must be in areas previously irradiated to ≥ 45 Gy
  • More than one recurrence allowed provided the first recurrence occurred > 6 months after the completion of prior radiotherapy

• Unresectable disease OR has high-risk features after resection (e.g., positive margins and/or extracapsular extension)

  • No signs of carotid exposure
• No primary nasopharyngeal or salivary gland tumor
• Equivocal pulmonary nodes on chest CT scan allowed provided they are < 1 cm, cannot be safely biopsied, or are negative on PET scan
• No distant metastasis

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• ANC ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
• Bilirubin < 1.5 mg/dL
• AST or ALT < 2 times upper limit of normal
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to submit prior radiotherapy records to assure that the spinal cord tolerance is not exceeded

• No active cardiac disease, including any of the following:

  • Unstable angina
  • Uncontrolled hypertension
  • Myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass graft or percutaneous transluminal coronary angioplasty)
  • Uncontrolled arrhythmia
  • Congestive heart failure
  • At least 3 heart-related hospitalizations within the past year
• No severe chronic obstructive pulmonary disease requiring ≥ 3 hospitalizations within the past year
• No concurrent medical illness that would impair patient tolerance to therapy or limit survival
• No other invasive malignancy within the past 2 years
• No pre-existing peripheral sensory neuropathy ≥ grade 2
• No prior severe infusion reaction to a monoclonal antibody
• No prisoners or individuals who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior surgery
• Prior cisplatin and cetuximab allowed
• At least 6 months since prior radiotherapy or chemotherapy
• No prior radiotherapy > 75 Gy

• No prior chemotherapy for recurrent head and neck cancer

  • Prior chemotherapy as a component of the primary treatment allowed

• No prior combination cisplatin, cetuximab, and radiotherapy for recurrent head and neck cancer

  • Patients with a new primary head and neck cancer whose prior primary head and neck cancer was treated with concurrent cisplatin, cetuximab, and radiotherapy are eligible provided it has been > 6 months since treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm: Chemotherapy with Concurrent Radiation therapy; Nab-Paclitaxel, Cetuximab, Cisplatin, and Radiation Therapy intensity-modulated radiation therapy	Drug: cetuximab; cetuximab; Other Names: chemo; Drug: cisplatin; cisplatin; Other Names: chemo; Radiation: intensity-modulated radiation therapy; IMRT; Other Names: IMRT; Drug: Nab-Paclitaxel; Nab-Paclitaxel; Other Names: chemo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	The 2-year PFS was measured from the date of enrollment to the first occurrence of new metastatic lesions, objective tumor progression, or death. The combination of cisplatin and cetuximab concurrent with radiation therapy for head and neck cancer has shown to have a favorable PFS. Patients were followed until death or from 7.5 months to 63.6 months (median 25.6 months) in those alive at last evaluation.	2 year from the date of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Acute and Late Toxicities	Incidence rate of acute and late toxicities of grade 3 or higher was measured after each treatment cycle was over. The most common late toxicities defined as toxicity occurring more than 90 days after treatment included laryngeal edema and xerostomia.	6 months within the end of treatment

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center

Publications and helpful links

General Publications

• Awan MJ, Nedzi L, Wang D, Tumati V, Sumer B, Xie XJ, Smith I, Truelson J, Hughes R, Myers LL, Lavertu P, Wong S, Yao M. Final results of a multi-institutional phase II trial of reirradiation with concurrent weekly cisplatin and cetuximab for recurrent or second primary squamous cell carcinoma of the head and neck. Ann Oncol. 2018 Apr 1;29(4):998-1003. doi: 10.1093/annonc/mdy018.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2008
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (Estimate): February 2, 2009

Study Record Updates

• Last Update Posted (Actual): August 21, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: tongue cancer; squamous cell carcinoma; recurrent paranasal sinus and nasal cavity cancer; recurrent hypopharynx Cancer; recurrent larynx Cancer; recurrent verrucous carcinoma; recurrent oral cavity cancer; recurrent metastatic occult primary cancer; recurrent oropharynx cacner
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Cisplatin; Cetuximab
• Other Study ID Numbers: CDR0000632295; SCCC-04308; CA 225314; 112008-004