Clinical trial NCT01332266: E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Official title: An Open-Label, Multicenter, Randomized, Phase 1b/2 Study of E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Keywords: Cancer
head and neck
squamous cell carcinoma of the head and neck
phase 1b
phase 2
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: PharmaBio Development Inc.
First posted: 2011-04-11
Enrollment: 95
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 determine whether participants with platinum-resistant squamous cell carcinoma of the head and neck (SCCHN) who receive either E7050 administered with cetuximab or cetuximab alone experience greater benefit.

Detailed description: This open-label, multicenter, randomized study will consist of a Phase 1b: a safety run-in period with 3 ascending doses of E7050 in combination with cetuximab; and a Phase 2 portion: a randomized 2-arm period. Approximately 95 participants with platinum-resistant squamous cell carcinoma of the head and neck will be enrolled in the study (10-15 participants in the Phase 1b portion and 80 participants in the Phase 2 portion). Participants will only participate in either the Phase 1b or the Phase 2 portion of the study.

In the Phase 2 portion, participants will receive study treatment (E7050 plus cetuximab or cetuximab alone) for approximately six 28-day cycles (24 weeks). Beyond 24 weeks, participants who are experiencing clinical benefit may continue E7050 plus cetuximab, cetuximab alone or E7050 alone (Arm 1), or may continue cetuximab alone (Arm 2), depending on the original randomization treatment arm, for as long as clinical benefit is sustained and the treatment is well tolerated.

Eligibility criteria: Inclusion Criteria:

* Platinum-resistant (defined as failure to respond to treatment with a platinum agent or recurrence of disease after initial response to platinum within 12 months of completing therapy), locally advanced, recurrent and/or metastatic SCCHN, which is untreatable by surgical resection or radiation therapy
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
* Blood pressure must be well-controlled. Participants must have no history of hypertensive crisis or hypertensive encephalopathy; Adequate end organ function

Exclusion Criteria

* Nasopharyngeal tumors
* Previously received E7050, anti-angiogenic therapy, or anti-epidermal growth factor receptor (EGFR) therapy (prior anti-angiogenic/EGFR therapy is permitted in Phase 1b only. Prior cetuximab is permitted if administered in combination with radiation
* Presence of brain metastases, unless the participant has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization
* Palliative radiotherapy is not permitted throughout the study period
* Clinically significant hemoptysis
* Serious non-healing wound, ulcer, or active bone fracture
* Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for a major surgical procedure during the course of the study
* Clinically significant gastrointestinal bleeding within 6 months prior to first dose.

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
timeFrame: Cycle 1 (Cycle length is equal to [=] 28 days)
measure: Phase 1b: Plasma Concentration of Golvatinib When Given in Combination With Cetuximab
timeFrame: Cycle 1: 0-48 hours post-dose (Each cycle=28 days)
measure: Phase 2: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 5 years 11 months
measure: Phase 2: Number of Participants With Markedly Abnormal Vital Sign Values
timeFrame: Up to 4 years 4 months
measure: Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
timeFrame: Up to 4 years 4 months
measure: Phase 2: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values
timeFrame: Up to 4 years 4 months
Secondary outcomes:
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 4 years 4 months)
measure: Phase 2: Percentage of Participants With PFS at Week 12
timeFrame: At Week 12
measure: Phase 2: Time to Progression (TTP)
timeFrame: From the date of randomization until the date of PD (Up to approximately 4 years 4 months)
measure: Phase 2: Overall Survival (OS)
timeFrame: From the date of randomization until the date of death (Up to approximately 4 years 4 months)
measure: Phase 2: Percentage of Participants With Overall Response
timeFrame: From the date of randomization until CR or PR (Up to approximately 4 years 4 months)
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Fort Myers
country: United States
state: Florida
city: Boston
country: United States
state: Massachusetts
city: Saint Louis
country: United States
state: Missouri
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Nashville
country: United States
state: Tennessee
city: Goyang-si
country: Korea, Republic of
state: Gyeonggi-do
city: Hwasun
country: Korea, Republic of
state: Jeollanam-do
city: Busan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Sumy
country: Ukraine
city: London
country: United Kingdom
state: Greater London
city: Manchester
country: United Kingdom
state: Greater Manchester
city: Glasgow
country: United Kingdom
state: Strathclyde
Study officials:
References: