NCT01332266

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

Completed Phase 1, PHASE2 Results posted Last updated 3 January 2022

What this trial tests

Phase 1, PHASE2 trial testing E7050 in Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck in 95 participants. Completed in 4 September 2017.

Timeline

19 September 2011

Primary endpoint
31 January 2016

4 September 2017

Quick facts

Lead sponsor	Eisai Inc.
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	95
Start date	19 September 2011
Primary completion	31 January 2016
Estimated completion	4 September 2017
Sites	23 locations across United Kingdom, United States, Ukraine, South Korea

Drugs / interventions tested

• E7050 — full drug profile →
• Cetuximab (cetuximab) — full drug profile →

Conditions studied

• Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck — all drugs for Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck →

Sponsor

Eisai Inc. — full company profile →

Who can join

18 and older, any sex, with Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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)

Group	Value	95% CI
Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2	0
Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2	0
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2	0

Phase 2: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) Primary · Up to 5 years 11 months

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

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	21
Phase 2: Arm 2: Cetuximab 400 mg/m^2	21

Phase 2: Number of Participants With Markedly Abnormal Vital Sign Values Primary · Up to 4 years 4 months

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	0
Phase 2: Arm 2: Cetuximab 400 mg/m^2	0

Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings Primary · Up to 4 years 4 months

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.

General Appearance

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	5
Phase 2: Arm 2: Cetuximab 400 mg/m^2	6

HEENT

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	20
Phase 2: Arm 2: Cetuximab 400 mg/m^2	17

Neck

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	24
Phase 2: Arm 2: Cetuximab 400 mg/m^2	22

Heart

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	1
Phase 2: Arm 2: Cetuximab 400 mg/m^2	0

Chest (Including Lungs)

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	4
Phase 2: Arm 2: Cetuximab 400 mg/m^2	5

Abdomen

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	6
Phase 2: Arm 2: Cetuximab 400 mg/m^2	3

Extremities

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	2
Phase 2: Arm 2: Cetuximab 400 mg/m^2	0

Skin

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	4
Phase 2: Arm 2: Cetuximab 400 mg/m^2	5

Phase 2: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values Primary · Up to 4 years 4 months

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	0
Phase 2: Arm 2: Cetuximab 400 mg/m^2	0

Phase 2: Progression-free Survival (PFS) Secondary · 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)

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 compl

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	15.71	12.14 – 23.86
Phase 2: Arm 2: Cetuximab 400 mg/m^2	15.71	9.29 – 18.71

Phase 2: Percentage of Participants With PFS at Week 12 Secondary · 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 M

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	68.9	50.79 – 81.44
Phase 2: Arm 2: Cetuximab 400 mg/m^2	59.4	41.90 – 73.23

Phase 2: Time to Progression (TTP) Secondary · From the date of randomization until the date of PD (Up to approximately 4 years 4 months)

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.

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	15.43	12.14 – 23.14
Phase 2: Arm 2: Cetuximab 400 mg/m^2	16.00	9.29 – 19.14

Phase 2: Overall Survival (OS) Secondary · From the date of randomization until the date of death (Up to approximately 4 years 4 months)

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.

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	39.71	28.43 – 49.71
Phase 2: Arm 2: Cetuximab 400 mg/m^2	36.71	28.00 – 44.43

Phase 2: Percentage of Participants With Overall Response Secondary · From the date of randomization until CR or PR (Up to approximately 4 years 4 months)

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.

Group	Value	95% CI
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2	9.5	0.7 – 18.4
Phase 2: Arm 2: Cetuximab 400 mg/m^2	4.9	0 – 11.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 5 years 11 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

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

Serious: 1/4 (25%)

Deaths: 3/4

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

Serious: 4/5 (80%)

Deaths: 3/5

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

Serious: 2/3 (67%)

Deaths: 2/3

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

Serious: 15/42 (36%)

Deaths: 33/42

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

Serious: 15/41 (37%)

Deaths: 36/41

Serious adverse events (39 terms)

Reaction	System	Phase 1b: Cohort 1: Golvat…	Phase 1b: Cohort 2: Golvat…	Phase 1b: Cohort 3: Golvat…	Phase 2: Arm 1: Golvatinib…	Phase 2: Arm 2: Cetuximab …
Pneumonia	Infections and infestations	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—
Tumour Haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Upper Airway Obstruction	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Haemorrhage Subcutaneous	Skin and subcutaneous tissue disorders	—	—	—	—	—
Pericardial Effusion	Cardiac disorders	—	—	—	—	—
Haematemesis	Gastrointestinal disorders	—	—	—	—	—
Mechanical Ileus	Gastrointestinal disorders	—	—	—	—	—
Oral Cavity Fistula	Gastrointestinal disorders	—	—	—	—	—
Rectal Haemorrhage	Gastrointestinal disorders	—	—	—	—	—
Adverse Drug Reaction	General disorders	—	—	—	—	—
Pyelonephritis Acute	Infections and infestations	—	—	—	—	—
Staphylococcal Infection	Infections and infestations	—	—	—	—	—
Tuberculosis	Infections and infestations	—	—	—	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—	—	—	—
Alcohol Poisoning	Injury, poisoning and procedural complications	—	—	—	—	—
Post Procedural Haemorrhage	Injury, poisoning and procedural complications	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—

Other adverse events (88 terms — click to expand)

Reaction	System	Phase 1b: Cohort 1: Golvat…	Phase 1b: Cohort 2: Golvat…	Phase 1b: Cohort 3: Golvat…	Phase 2: Arm 1: Golvatinib…	Phase 2: Arm 2: Cetuximab …
Nausea	Gastrointestinal disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Alanine Aminotransferase Increased	Investigations	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Aspartate Aminotransferase Increased	Investigations	—	—	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—	—	—
Dermatitis Acneiform	Skin and subcutaneous tissue disorders	—	—	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—	—	—
Weight Decreased	Investigations	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Dry Skin	Skin and subcutaneous tissue disorders	—	—	—	—	—
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	—	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—	—
Paronychia	Infections and infestations	—	—	—	—	—
Skin Fissures	Skin and subcutaneous tissue disorders	—	—	—	—	—
Mucosal Inflammation	General disorders	—	—	—	—	—
Abdominal Pain Upper	Gastrointestinal disorders	—	—	—	—	—
Blood Alkaline Phosphatase Increased	Investigations	—	—	—	—	—
Blood Lactate Dehydrogenase Increased	Investigations	—	—	—	—	—
Pain in Extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Neck Pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Chest Pain	General disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Haematuria	Renal and urinary disorders	—	—	—	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—
Lethargy	Nervous system disorders	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Anaemia, Pneumonia Aspiration, Dysphagia, Tumour Haemorrhage, Abdominal Pain, Nausea, Vomiting.

Data from ClinicalTrials.gov NCT01332266 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
   Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
2. Targeting the HGF/Met signaling pathway in cancer therapy.
   Cecchi F, Rabe DC, Bottaro DP. · · 2012 · cited 180× · PMID 22530990 · DOI 10.1517/14728222.2012.680957
3. Clinical update on cancer: molecular oncology of head and neck cancer.
   Suh Y, Amelio I, Guerrero Urbano T, Tavassoli M. · · 2014 · cited 132× · PMID 24457962 · DOI 10.1038/cddis.2013.548
4. Small molecule inhibitors targeting the cancers.
   Liu GH, Chen T, Zhang X, Ma XL, et al · · 2022 · cited 127× · PMID 36254250 · DOI 10.1002/mco2.181
5. Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer.
   Raj S, Kesari KK, Kumar A, Rathi B, et al · · 2022 · cited 111× · PMID 35081970 · DOI 10.1186/s12943-022-01503-1
6. Activated HGF-c-Met Axis in Head and Neck Cancer.
   Arnold L, Enders J, Thomas SM. · · 2017 · cited 53× · PMID 29231907 · DOI 10.3390/cancers9120169
7. Clinical Development of Molecular Targeted Therapy in Head and Neck Squamous Cell Carcinoma.
   Gougis P, Moreau Bachelard C, Kamal M, Gan HK, et al · · 2019 · cited 39× · PMID 32337482 · DOI 10.1093/jncics/pkz055
8. Genomically personalized therapy in head and neck cancer.
   Aung KL, Siu LL. · · 2016 · cited 20× · PMID 31093332 · DOI 10.1186/s41199-016-0004-y