Radiation + Cisplatin or Panitumumab in Locally Advanced Stage III or Stage IV Head and Neck Cancer

NCT00820248 | Completed Phase 3 Results DMC

• 3 other identifiers: HN6CAN-NCIC-HN6CDR0000630159
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 19

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy in higher doses over a shorter period of time may kill more tumor cells and have fewer side effects. 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. Monoclonal antibodies, such as panitumumab, 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. It is not yet known whether giving standard radiation therapy together with high-dose cisplatin is more effective than giving higher-dose radiation therapy together with panitumumab in treating patients with locally advanced head and neck cancer. PURPOSE: This randomized phase III trial is comparing two radiation therapy regimens to see how well they work when given together with cisplatin or panitumumab in treating patients with locally advanced stage III or stage IV head and neck cancer.

Conditions

Head and Neck Cancer

Keywords

stage III squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage III verrucous carcinoma of the larynx; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV verrucous carcinoma of the larynx; stage IV squamous cell carcinoma of the oropharynx; stage III verrucous carcinoma of the oral cavity; stage III squamous cell carcinoma of the lip and oral cavity; stage IV verrucous carcinoma of the oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Rate

  The progression event is defined by first event of the following, Local-regional progression or recurrence Distant metastasis Non-protocol RT, chemotherapy, or biologic therapy without documentation of the site of failure Surgery of primary site with tumour present/unknown Neck dissection with tumour present/unknown, \> 15 weeks from end of RT Death due to study cancer or from unknown causes or any other reason Number of patients with and without progression event will be reported.

  6.2 years

Secondary Outcomes (1)

• Overall Survival Rate

  6.2 years

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients undergo standard fractionation radiotherapy (IMRT or 3D CRT) once daily, 5 days a week, for 7 weeks. Patients receive cisplatin IV over 1 hour on days 1, 22, and 43 of radiotherapy.

Drug: cisplatin; Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy

Arm II

EXPERIMENTAL

Patients undergo accelerated fractionation radiotherapy (IMRT or 3D CRT) once or twice daily, 5 days a week, for 6 weeks. Patients receive panitumumab IV over 30-90 minutes 1 week prior to and on days 15 and 36 of radiotherapy.

Biological: panitumumab; Radiation: 3-dimensional conformal radiation therapy; Radiation: accelerated radiation therapy; Radiation: intensity-modulated radiation therapy

Interventions

panitumumab BIOLOGICAL

Given IV

Arm II

cisplatin DRUG

Given IV

Arm I

3-dimensional conformal radiation therapy RADIATION

Patients undergo radiotherapy

Arm I; Arm II

accelerated radiation therapy RADIATION

Patients undergo accelerated fractionation radiotherapy

Arm II

intensity-modulated radiation therapy RADIATION

Patients undergo radiotherapy

Arm I; Arm II

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically and/or cytologically confirmed (primary lesion or regional lymph nodes) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx * Locally advanced disease, defined by any of the following criteria: * Any T, N+, M0 * T3-4, N0, M0 * No current history of unknown primary squamous cell carcinoma of the head and neck, primary nasopharyngeal, paranasal, or salivary gland tumors of the head and neck PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Absolute granulocyte count ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST or ALT ≤ 3 times ULN * Creatinine clearance \> 50 mL/min * Magnesium \> 0.5 mmol/L * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment * Must be accessible for treatment and follow-up * Able (sufficiently fluent) and willing to complete the quality of life (QOL) and swallowing QOL questionnaires in either English or French * Must be assessed by a radiation oncologist and medical oncologist and deemed suitable for study participation * No other malignancies within the past 5 years, except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other curatively treated solid tumors * No history of allergic or hypersensitivity reactions to any of the study drugs or their excipients * No prior or concurrent interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) on baseline CT scan * No peripheral neuropathy ≥ grade 2 (CTCAE v3.0) * No hearing loss/tinnitus ≥ grade 3 (CTCAE v3.0) * No thromboembolic event within the past 12 months despite being treated with anticoagulation drugs * Prior thromboembolic event \> 12 months allowed provided patient is stable on anticoagulation or on preventative anticoagulation * None of the following allowed: * Myocardial infarction within the past 12 months * Uncontrolled severe congestive heart failure * Unstable angina * Active cardiomyopathy * Unstable ventricular arrhythmia * Uncontrolled hypertension * Uncontrolled psychiatric disorder * Active serious infection * Active peptic ulcer disease * Any other medical condition that might interfere with protocol therapy delivery PRIOR CONCURRENT THERAPY: * No prior surgical treatment except diagnostic biopsy for this disease * No prior induction chemotherapy for this disease * No prior radiation to the head and neck region that would result in overlap of fields for this study * No prior cisplatin or carboplatin chemotherapy * No prior targeted anti-EGFR therapy of any kind * At least 30 days since any prior investigational agent * No concurrent granulocytic growth factors (e.g., filgrastim \[G-CSF\]) during radiotherapy * No concurrent erythropoietic growth factors, pilocarpine, amifostine, other anticancer therapy (e.g., cytotoxic agents, biological response modifiers, immunotherapy, or hormonal therapy), or other investigational drug therapy * The following radiological investigations must be done within 8 weeks of randomization: * MRI or CT of the head and neck * CT chest

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (19)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, AIB 3V6, Canada

Location

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Health Research Institute - General Division

Ottawa, Ontario, K1H 8L6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (3)

• Ringash J, Waldron JN, Siu LL, Martino R, Winquist E, Wright JR, Nabid A, Hay JH, Hammond A, Sultanem K, Hotte S, Leong C, El-Gayed AA, Naz F, Ramchandar K, Owen TE, Montenegro A, O'Sullivan B, Chen BE, Parulekar WR. Quality of life and swallowing with standard chemoradiotherapy versus accelerated radiotherapy and panitumumab in locoregionally advanced carcinoma of the head and neck: A phase III randomised trial from the Canadian Cancer Trials Group (HN.6). Eur J Cancer. 2017 Feb;72:192-199. doi: 10.1016/j.ejca.2016.11.008. Epub 2016 Dec 29.

  PMID: 28040660 BACKGROUND

• Siu LL, Waldron JN, Chen BE, Winquist E, Wright JR, Nabid A, Hay JH, Ringash J, Liu G, Johnson A, Shenouda G, Chasen M, Pearce A, Butler JB, Breen S, Chen EX, FitzGerald TJ, Childs TJ, Montenegro A, O'Sullivan B, Parulekar WR. Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma: A Randomized Clinical Trial. JAMA Oncol. 2017 Feb 1;3(2):220-226. doi: 10.1001/jamaoncol.2016.4510.

  PMID: 27930762 RESULT

• Cuffe S, Hon H, Tobros K, Espin-Garcia O, Brhane Y, Harland L, Fadhel E, Eng L, LaDelfa A, Waldron J, Siu LL, Chen BE, Xu W, Simmons C, Kassam Z, Montenegro A, Parulekar WR, Liu G. Cancer patients' acceptability of incorporating an epidemiology questionnaire within a clinical trial. Clin Trials. 2015 Jun;12(3):237-45. doi: 10.1177/1740774514568689. Epub 2015 Jan 29.

  PMID: 25633805 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Panitumumab; Cisplatin; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Wendy Parulekar
• Organization: Canadian Cancer Trials Group

wparulekar@ctg.queensu.ca

613-533-6430

Study Officials

• Lillian L. Siu, MD, FRCPC

  Princess Margaret Hospital, Canada

  PRINCIPAL INVESTIGATOR

• John Waldron, MD

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2009
• First Posted: January 12, 2009
• Study Start: December 30, 2008
• Primary Completion: May 16, 2015
• Study Completion: February 17, 2017
• Last Updated: August 22, 2023
• Results First Posted: June 20, 2017

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (19)