Radiotherapy Plus Panitumumab Compared to Chemoradiotherapy With Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Cancer Clinical Trial

Official title:

A Phase 2 Randomized Trial of Radiotherapy Plus Panitumumab Compared to Chemoradiotherapy With Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00547157
• Other study ID #: 20062079
• Secondary ID: CONCERT2
• Status: Completed
• Phase: Phase 2
• First received: October 18, 2007
• Last updated: July 10, 2014
• Start date: November 2007
• Est. completion date: March 2012

Study information

• Verified date: July 2014
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentCzech Republic: State Institute for Drug ControlMexico: COFEPRISPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSpain: Agencia Española de Medicamentos y Productos SanitariosSwitzerland: Swissmedic (Swiss Agency for Therapeutic Products)United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to estimate, with pre-specified precision, the difference in local-regional control (LRC) rate at 2 years in subjects receiving chemoradiotherapy (CRT) or panitumumab plus radiotherapy (PRT) as first line treatment for locally advanced squamous cell carcinoma for the head and neck (SCCHN). A formal hypothesis will not be tested in this trial; however, the treatment arm difference in LRC rates at 2 years will be estimated.

Description:

Primary Objective: To estimate, with pre-specified precision, the difference in local-regional control (LRC) rate at 2 years in subjects receiving chemoradiotherapy (CRT) or panitumumab plus radiotherapy (PRT) as first line treatment for locally advanced squamous cell carcinoma for the head and neck (SCCHN).

Secondary Objectives: To estimate the difference between 2 treatment regimens (CRT vs PRT) on other measures of clinical benefit, including LRC, overall response rate (ORR), progression-free survival (PFS), overall survival (OS); and safety.

Tertiary Objectives: To estimate the difference in health-related quality of life (HRQoL) and performance status in subjects receiving PRT or CRT.

Exploratory Objectives: To investigate potential biomarker development based on assessment of blood and tumor and the proposed mechanism of actions of study drugs. In addition, to investigate the effect of genetic variation in cancer genes and drug target genes on SCCHN and subject response to study drugs (separate informed consent required).

Hypothesis: A formal hypothesis will not be tested in this trial; however, the treatment arm difference in LRC rates at 2 years will be estimated.

Study Design: This is a phase 2, open-label, randomized, multicenter study. Eligible subjects will be randomized in a 2:3 ratio to either of the following regimens:

Arm 1 CRT:

• Accelerated fractionation RT: 70 to 72 Gy - delivered over 6 to 6.5 weeks

• Cisplatin: 100 mg/m2 (given on days 1 and 22 of RT) or

Arm 2 PRT:

• Accelerated fractionation RT: 70 to 72 Gy - delivered over 6 to 6.5 weeks

• Panitumumab: 9.0 mg/kg Q3W (given on days 1, 22, and 43 of RT)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: March 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Histologically or cytologically confirmed SCC of the oral cavity, oropharynx, hypopharynx or larynx Stage III or Stage IVa-b (M0) disease according to the American Joint Committee on Cancer staging manual 6th edition (locally advanced) ECOG performance status of 0 or 1 Bidimensionally measurable disease >/= 10 mm in at least 1 dimension

Exclusion Criteria:

NO Primary tumor of the nasopharynx, sinuses, salivary gland, or skin NO Subjects requiring prophylactic tracheostomy NO Prior (or concomitant) malignancy (except non-melanomatous skin cancer or in situ cervical cancer), other than the study disease (SCCHN), unless treated with curative intent with no evidence of disease for >/= 3 years NO Prior treatment for locally advanced SSCHN NO Prior surgery for SCCHN (except nodal sampling or biopsy for study disease) NO Major surgery </= 28 days before randomization or minor surgery </= 14 days before randomization with the exception of feeding tube placement, dental extractions, central venous catheter placement, biopsies and nodal sampling

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms
• Oncology
• Squamous Cell Carcinoma

Intervention

Drug:
• Panitumumab
Arm 2 consists of panitmumab plus RT
• Cisplatin
Cisplatin

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (2)

Giralt J, Trigo J, Nuyts S, Ozsahin M, Skladowski K, Hatoum G, Daisne JF, Yunes Ancona AC, Cmelak A, Mesía R, Zhang A, Oliner KS, VanderWalde A. Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):221-32. doi: 10.1016/S1470-2045(14)71200-8. Epub 2015 Jan 15. — View Citation

Mesía R, Henke M, Fortin A, Minn H, Yunes Ancona AC, Cmelak A, Markowitz AB, Hotte SJ, Singh S, Chan AT, Merlano MC, Skladowski K, Zhang A, Oliner KS, VanderWalde A, Giralt J. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):208-20. doi: 10.1016/S1470-2045(14)71198-2. Epub 2015 Jan 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local Regional Control Rate at 2 Years	Kaplan-Meier estimate of Local regional control rate at 2 years. Local regional control rate will be measured according to the investigator's assessment of disease status based on all available data (ie, from clinical examination, radiologic assessments, pathology reports, and autopsy reports).	from study day 1 to 2 years	No
Secondary	Duration of Local Regional Control	Time from study day 1 to the date of first local-regional failure or to death due to any cause (whichever occurs first)	maximum follow up time 46.2 months	No
Secondary	Progression-free Survival	Time from first dose date till disease progression or death	maximum follow up time 46.2 months	No
Secondary	Overall Survival	Time from first dose date to death	maximum follow up time 46.2 months	No
Secondary	ORR by 6 Months - Central	ORR is Objective Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete or partial response is considered as objective response.	From randomization to 6 months	No
Secondary	CRR by 6 Months - Central	CRR is Complete Response Rate. Tumor assessments are based on central review of scans uisng a modification of the WHO criteria. Complete Response (CR) is defined as disappearance of all index lesions.	From randomization till 6 months	No

External Links

•   AmgenTrials clinical trials website