The starting dose of E7050 will be 50 mg given orally, twice-daily, in patients with advanced tumors that have progressed following effective therapy.

E7050

Takashi Sawada

The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of E7050 when administered orally twice daily to patients with advanced solid tumors.

Phase I, open-label, dose-escalation study to determine the maximum tolerated dose (MTD) of E7050 given orally, twice-daily, in patients with advanced tumors that have progressed following effective therapy.

A Study of E7050 Administered Orally to Patients With Advanced Solid Tumors

A Phase I Dose-finding Study of E7050 Administered Orally to Patients With Advanced Solid Tumors.

Eisai Co., Ltd.

Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Antineoplastic Agents, Immunological

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

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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

PharmaBio Development Inc.

Eisai Inc.

Participants with platinum-resistant SCCHN received golvatinib 200 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2

Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2

Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2

Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2

Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Phase 2: Arm 2: Cetuximab 400 mg/m^2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

ECOG: 0 (Fully Active)

ECOG: 1 (Restricted in Physical Activity; Ambulatory)

ECOG: 2 (Ambulatory and Capable of All Self-care)

ECOG: 3 (Capable of Only Limited Self-care)

ECOG: 4 (Completely Disabled)

ECOG: 5 (Dead)

Not Specified

ECOG PS is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0=Fully Active (Most Favorable Activity); 1=Restricted activity but ambulatory; 2=Ambulatory but unable to carry out work activities; 3=Limited Self-Care; 4=Completely Disabled, No self-care (Least Favorable Activity); 5=Dead.

Eastern Cooperative Oncology Group Performance Status (ECOG PS)

Safety population was defined as all participants enrolled and randomized into Phase 1b and Phase 2, except for those who drop out of study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment.

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.

Eisai Medical Information

Participants with platinum-resistant SCCHN received 200 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Participants with platinum-resistant SCCHN received 300 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment.

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)

Data was not collected and analyzed for this outcome measure because 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.

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)

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

General Appearance

HEENT

Neck

Heart

Chest (Including Lungs)

Abdomen

Extremities

Skin

Lymph Nodes

Neurologic

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

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

Modified Intent-to-Treat (MITT) analysis set included all participants randomized in the applicable study arm who received any comparator or study drug.

Phase 2: Progression-free Survival (PFS)

MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug.

Phase 2: Percentage of Participants With PFS at Week 12

Phase 2: Time to Progression (TTP)

MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug. Here "Overall number of participants analyzed" signifies participants with events (death).

Phase 2: Overall Survival (OS)

Participants with platinum-resistant squamous cell carcinoma of the head and neck received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After six cycles, at the discretion of the Investigator, participants experienced clinical benefit have continued for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Phase 2: Percentage of Participants With Overall Response

Participants with platinum-resistant squamous cell carcinoma of the head and neck (SCCHN) received golvatinib 200 milligram (mg) tablets, orally, once daily (run-in period) and cetuximab 400 milligram per square meter (mg/m\^2) intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining maximum tolerated dose (MTD) or Recommended Phase 2 dose (RP2D), until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of E7050 Administered Orally to Patients With Advanced Solid Tumors	NCT00921869	Solid Tumors	E7050	20 Years - 74 Years	Eisai Inc.
E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck	NCT01332266	Platinum-Resist...	E7050 Cetuximab	18 Years -	Eisai Inc.

Spots Global Cancer Trial Database for e7050

Every month we try and update this database with for e7050 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for e7050

Every month we try and update this database with for e7050 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for e7050 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.