Clinical trial NCT00547157: Radiotherapy Plus Panitumumab Compared to Chemoradiotherapy With Unresected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Head and Neck Cancer
Oncology
Squamous Cell Carcinoma
Keywords: head and neck
squamous cell carcinoma
radiotherapy
chemoradiotherapy
panitumumab
locally advanced head & neck cancer
EGFr
epidermal growth factor receptor
SCCHN
locally advanced SCCHN
HNC
epidermal growth factor
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2007-10-22
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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)

Eligibility criteria: 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

Primary outcomes:
measure: Local Regional Control Rate at 2 Years
timeFrame: from study day 1 to 2 years
Secondary outcomes:
measure: Duration of Local Regional Control
timeFrame: maximum follow up time 46.2 months
measure: Progression-free Survival
timeFrame: maximum follow up time 46.2 months
measure: Overall Survival
timeFrame: maximum follow up time 46.2 months
measure: ORR by 6 Months - Central
timeFrame: From randomization to 6 months
measure: CRR by 6 Months - Central
timeFrame: From randomization till 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Giralt J, Trigo J, Nuyts S, Ozsahin M, Skladowski K, Hatoum G, Daisne JF, Yunes Ancona AC, Cmelak A, Mesia 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.
citation: Mesia 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.