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

Primary Purpose

Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

E7050

Cetuximab

About this trial

This is an interventional treatment trial for Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck focused on measuring Cancer, head and neck, squamous cell carcinoma of the head and neck, phase 1b, phase 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

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

Phase 2

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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

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.

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

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.

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

Secondary Outcome Measures

Phase 2: Progression-free Survival (PFS)

PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on response evaluation criteria in solid tumor (RECIST) v1.1. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.

Phase 2: Percentage of Participants With PFS at Week 12

PFS rate at week 12 is defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS rate was estimated and analyzed using Kaplan Meier method.

Phase 2: Time to Progression (TTP)

TTP is defined as the time from the date of randomization until the date of PD based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.

Phase 2: Overall Survival (OS)

OS is defined as the time from the date of randomization until the date of death. OS was analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.

Phase 2: Percentage of Participants With Overall Response

Overall response rate is defined as percentage of participants with complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As planned, data for this endpoint was analyzed and collected till primary completion date.

Full Information

NCT ID

NCT01332266

First Posted

April 7, 2011

Last Updated

December 3, 2021

Sponsor

Eisai Inc.

Collaborators

PharmaBio Development Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01332266

Brief Title

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

2. Study Status

Record Verification Date

December 2017

Overall Recruitment Status

Completed

Study Start Date

September 19, 2011 (Actual)

Primary Completion Date

January 31, 2016 (Actual)

Study Completion Date

September 4, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Inc.

Collaborators

PharmaBio Development Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

95 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Active Comparator

Arm Description

Arm Title

Phase 2

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

E7050

Other Intervention Name(s)

Golvatinib

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cetuximab

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Description

Time Frame

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

Title

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

Time Frame

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

Title

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

Description

Time Frame

Up to 5 years 11 months

Title

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

Time Frame

Up to 4 years 4 months

Title

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

Description

Time Frame

Up to 4 years 4 months

Title

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

Time Frame

Up to 4 years 4 months

Secondary Outcome Measure Information:

Title

Phase 2: Progression-free Survival (PFS)

Description

Time Frame

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)

Title

Phase 2: Percentage of Participants With PFS at Week 12

Description

Time Frame

At Week 12

Title

Phase 2: Time to Progression (TTP)

Description

Time Frame

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

Title

Phase 2: Overall Survival (OS)

Description

Time Frame

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

Title

Phase 2: Percentage of Participants With Overall Response

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Facility Information:

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85715

Country

United States

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33905

Country

United States

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

City

Toledo

State/Province

Ohio

ZIP/Postal Code

43623

Country

United States

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

City

Goyang-si

State/Province

Gyeonggi-do

ZIP/Postal Code

410-769

Country

Korea, Republic of

City

Hwasun

State/Province

Jeollanam-do

ZIP/Postal Code

519-763

Country

Korea, Republic of

City

Busan

ZIP/Postal Code

602-739

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

110-744

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

City

Seoul

ZIP/Postal Code

138-736

Country

Korea, Republic of

City

Dnipropetrovsk

ZIP/Postal Code

49102

Country

Ukraine

City

Donetsk

ZIP/Postal Code

83003

Country

Ukraine

City

Donetsk

ZIP/Postal Code

83092

Country

Ukraine

City

Kharkiv

ZIP/Postal Code

61024

Country

Ukraine

City

Kyiv

ZIP/Postal Code

3057

Country

Ukraine

City

Sumy

ZIP/Postal Code

40005

Country

Ukraine

City

London

State/Province

Greater London

ZIP/Postal Code

NW1 2BU

Country

United Kingdom

City

Manchester

State/Province

Greater Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

City

Glasgow

State/Province

Strathclyde

ZIP/Postal Code

G12 0YN

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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