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Platinum-Resistant Squamous Cell Carcinoma of the Head and NeckPhase 1/2NCT01332266

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

A Phase 1/2 study testing E7050 and Cetuximab in people with Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck, run by Eisai Inc. at 23 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
E7050 and Cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
23 sitesin 4 countries
Study dates
19 Sep 2011to 4 Sep 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

23 sites in 4 countries.

23 sites in 4 countries

United States7 sites

  • Study site

    Boston, Massachusetts, 02111

  • Study site

    Fort Myers, Florida, 33905

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    Oklahoma City, Oklahoma, 73104

  • Study site

    St Louis, Missouri, 63110

  • Study site

    Toledo, Ohio, 43623

  • Study site

    Tucson, Arizona, 85715

Other trials in United States

South Korea7 sites

  • Study site

    Busan, 602-739

  • Study site

    Goyang-si, Gyeonggi-do, 410-769

  • Study site

    Hwasun, Jeollanam-do, 519-763

  • Study site

    Seoul, 110-744

  • Study site

    Seoul, 120-752

  • Study site

    Seoul, 135-710

  • Study site

    Seoul, 138-736

Other trials in South Korea

Ukraine6 sites

  • Study site

    Dnipropetrovsk, 49102

  • Study site

    Donetsk, 83003

  • Study site

    Donetsk, 83092

  • Study site

    Kharkiv, 61024

  • Study site

    Kyiv, 3057

  • Study site

    Sumy, 40005

Other trials in Ukraine

United Kingdom3 sites

  • Study site

    Glasgow, Strathclyde, G12 0YN

  • Study site

    London, Greater London, NW1 2BU

  • Study site

    Manchester, Greater Manchester, M20 4BX

Other trials in United Kingdom

About this study

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

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.

Read the 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.

Being tested
E7050, Cetuximab
Keywords
Cancer, head and neck, squamous cell carcinoma of the head and neck, phase 1b, phase 2
Medical subject headings
Neoplasms, Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E7050Drug

    Also called Golvatinib

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

  • CetuximabDrug

    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.

Study groups in NCT01332266
Study groupRoleWhat they receive
Active Comparator; Phase 1b: Cohort 1,2,and 3Active comparatorPhase 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
Receives: Drug: E7050; Drug: Cetuximab
Phase 2Active comparatorPhase 2: Arm 1; MTD E7050 + 250 mg/m2 cetuximab Arm 2; 250 mg/m2 cetuximab
Receives: Drug: E7050; Drug: Cetuximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

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

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

  3. 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.

    Measured: Up to 5 years 11 months

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

    Measured: Up to 4 years 4 months

  5. 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.

    Measured: Up to 4 years 4 months

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

    Measured: Up to 4 years 4 months

Secondary outcomes (5)

  1. 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.

    Measured: 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)

  2. 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.

    Measured: At Week 12

  3. 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.

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

  4. 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.

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

  5. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Apr 2011 (estimated)
  2. Study start19 Sep 2011
  3. Primary completion31 Jan 2016
  4. Study completion4 Sep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01332266
Sponsor's protocol ID
E7050-702
Other IDs
2011-000773-31
Status last verified
Dec 2017
First submitted
7 Apr 2011
Last updated
3 Jan 2022
Data monitoring committee
No
FDA-regulated drug
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing E7050 and Cetuximab in people with Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck, run by Eisai Inc. at 23 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, South Korea, Ukraine, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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) (time frame: Cycle 1 (Cycle length is equal to [=] 28 days)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01332266.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2022.

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