E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck

NCT01332266 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: E7050-7022011-000773-31
• Study Type: interventional
• Target: 95
• Locations: 4 countries
• Sites: 23

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.

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

Outcome Measures

Primary Outcomes (6)

• 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)

  DLT:adverse events graded as NCI CTCAEv4.0 occurring less than or equal to(\<=)28 days after treatment.Events as: Non-hematological: 1)Grade greater than or equal to(\>=)3 peripheral neuropathy; 2)Grade 3 fatigue or 2 point decline in eastern cooperative oncology group performance status that persisted for greater than(\>)7 days; 3)Grade \>=3 nausea,vomiting despite optimal antiemetic treatment; 4)Any nonhematologic toxicity of Grade \>=3, with exceptions as alopecia,single laboratory values out of normal range,hypersensitivity reaction. Hematological 1)Grade 4 neutropenia lasting \>7 days; 2)Febrile neutropenia as fever \>=38.5 degree celsius with absolute neutrophil count less than(\<)1.0\*10\^9 per liter(/L); 3)Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4)Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1)Study drug related death; 2)Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria.

  Cycle 1 (Cycle length is equal to [=] 28 days)

• Phase 1b: Plasma Concentration of Golvatinib When Given in Combination With Cetuximab

  Cycle 1: 0-48 hours post-dose (Each cycle=28 days)

• Phase 2: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs)

  TEAEs are defined as an adverse event that has an onset date, or a worsening in severity from baseline (pre-golvatinib), on or after the first dose of golvatinib. The severity was graded according to CTCAE v4.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event.

  Up to 5 years 11 months

• Phase 2: Number of Participants With Markedly Abnormal Vital Sign Values

  Up to 4 years 4 months

• Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings

  Physical examination was performed and included evaluation of 1) General appearance, 2) Head; Eyes; Ears; Nose; Throat (HEENT), 3) Neck, 4) Heart, 5) Chest (Including Lungs), 6) Abdomen, 7) Extremities, 8) Skin, 9) Lymph Nodes, and 10) neurological status. Here, number of participants with markedly abnormal physical examinations were reported.

  Up to 4 years 4 months

• Phase 2: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values

  Up to 4 years 4 months

Secondary Outcomes (5)

• Phase 2: Progression-free Survival (PFS)

  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)

• Phase 2: Percentage of Participants With PFS at Week 12

  At Week 12

• Phase 2: Time to Progression (TTP)

  From the date of randomization until the date of PD (Up to approximately 4 years 4 months)

• Phase 2: Overall Survival (OS)

  From the date of randomization until the date of death (Up to approximately 4 years 4 months)

• Phase 2: Percentage of Participants With Overall Response

  From the date of randomization until CR or PR (Up to approximately 4 years 4 months)

Study Arms (2)

Active Comparator; Phase 1b: Cohort 1,2,and 3

ACTIVE COMPARATOR

Phase 1b: Cohort 1; 200 mg E7050 + 250 mg/m2 cetuximab Cohort 2; 300 mg E7050 + 250 mg/m2 cetuximab Cohort 3; 400mg E7050 + 250mg/m2 cetuximab Phase 2: Arm 1; MTD E7050 + 250 mg cetuximab Arm 2; 250 mg cetuximab Interventions: Drug cetuximab

Drug: E7050; Drug: Cetuximab

Phase 2

ACTIVE COMPARATOR

Phase 2: Arm 1; MTD E7050 + 250 mg/m2 cetuximab Arm 2; 250 mg/m2 cetuximab

Drug: E7050; Drug: Cetuximab

Interventions

E7050 DRUG

E7050 given orally at 200, 300, or 400 mg once daily.

Also known as: Golvatinib

Active Comparator; Phase 1b: Cohort 1,2,and 3; Phase 2

Cetuximab DRUG

Cetuximab is given at an initial dose of 400 mg/m2 given as a 2-hour intravenous (IV) infusion on Day 1 of Cycle 1, followed by a dose of 250 mg/m2 given as a 1-hour IV infusion on Day 8, Day 15, and Day 22 of Cycle 1, and Day 1, Day 8, Day 15, and Day 22 of each subsequent cycle.

Active Comparator; Phase 1b: Cohort 1,2,and 3; Phase 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eisai Inc.: lead
• PharmaBio Development Inc.: collaborator

Study Sites (23)

Unknown Facility

Tucson, Arizona, 85715, United States

Location

Unknown Facility

Fort Myers, Florida, 33905, United States

Location

Unknown Facility

Boston, Massachusetts, 02111, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Toledo, Ohio, 43623, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73104, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

Unknown Facility

Hwasun, Jeollanam-do, 519-763, South Korea

Location

Unknown Facility

Busan, 602-739, South Korea

Location

Unknown Facility

Seoul, 110-744, South Korea

Location

Unknown Facility

Seoul, 120-752, South Korea

Location

Unknown Facility

Seoul, 135-710, South Korea

Location

Unknown Facility

Seoul, 138-736, South Korea

Location

Unknown Facility

Dnipropetrovsk, 49102, Ukraine

Location

Unknown Facility

Donetsk, 83003, Ukraine

Location

Unknown Facility

Donetsk, 83092, Ukraine

Location

Unknown Facility

Kharkiv, 61024, Ukraine

Location

Unknown Facility

Kyiv, 3057, Ukraine

Location

Unknown Facility

Sumy, 40005, Ukraine

Location

Unknown Facility

London, Greater London, NW1 2BU, United Kingdom

Location

Unknown Facility

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Unknown Facility

Glasgow, Strathclyde, G12 0YN, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

N-(2-fluoro-4-((2-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)carbonylaminopyridin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; Cetuximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

No pharmacokinetic analysis was conducted in this study due to incomplete pharmacokinetic sample bioanalysis due to unresolved queries leading to inadequate calculations and limited data interpretability.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

+1-888-274-2378

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 11, 2011
• Study Start: September 19, 2011
• Primary Completion: January 31, 2016
• Study Completion: September 4, 2017
• Last Updated: January 3, 2022
• Results First Posted: January 3, 2022

Record last verified: 2017-12

Locations

UA (6); KR (7); US (7); GB (3)