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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
PharmaBio Development Inc.
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01332266
First received: April 7, 2011
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to determine whether patients with Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck who receive either E7050 administered with Cetuximab or Cetuximab alone experience greater benefit


Condition Intervention Phase
Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Drug: E7050
Drug: Cetuximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Safety Parameters- Adverse Events [ Time Frame: until study termination; 3 years ] [ Designated as safety issue: Yes ]

    Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with cetuximab in patients with platinum-resistant, recurrent and/or metastatic squamous cell carcinoma for the head and neck (SCCHN).

    Phase II: to evaluate the safety and tolerability of E7050 administered in combination with cetuximab compared with cetuximab alone in patients with platinum-resistant, recurrent and/or metastatic SCCHN.


  • Safety Parameter- concomitant medications [ Time Frame: until study termination; 3 years ] [ Designated as safety issue: Yes ]

    Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with cetuximab in patients with platinum-resistant, recurrent and/or metastatic squamous cell carcinoma for the head and neck (SCCHN).

    Phase II: to evaluate the safety and tolerability of E7050 administered in combination with cetuximab compared with cetuximab alone in patients with platinum-resistant, recurrent and/or metastatic SCCHN.


  • Safety Parameter- Lab tests [ Time Frame: Day 1 and every 28 days until study termination; 3 years ] [ Designated as safety issue: Yes ]

    Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with cetuximab in patients with platinum-resistant, recurrent and/or metastatic squamous cell carcinoma for the head and neck (SCCHN).

    Phase II: to evaluate the safety and tolerability of E7050 administered in combination with cetuximab compared with cetuximab alone in patients with platinum-resistant, recurrent and/or metastatic SCCHN.


  • Safety Parameter- ECGs [ Time Frame: Screening and 28 days after end of therapy; 3 years ] [ Designated as safety issue: Yes ]

    Phase Ib: to determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with cetuximab in patients with platinum-resistant, recurrent and/or metastatic squamous cell carcinoma for the head and neck (SCCHN).

    Phase II: to evaluate the safety and tolerability of E7050 administered in combination with cetuximab compared with cetuximab alone in patients with platinum-resistant, recurrent and/or metastatic SCCHN.



Secondary Outcome Measures:
  • Efficacy Parameter [ Time Frame: Time Frame: Time to progression (TTP)-until the date of first documented progression of such patient's disease or death for 3 years ] [ Designated as safety issue: No ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with cetuximab in patients with platinum-resistant, recurrent and/or metastatic SCCHN;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with cetuximab as compared with cetuximab alone in patients with platinum-resistant, recurrent and/or metastatic SCCHN..


  • Efficacy Parameter [ Time Frame: Overall survival (OS)-until the date of first documented progression of such patient's disease or death for 3 years ] [ Designated as safety issue: No ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with cetuximab in patients with platinum-resistant, recurrent and/or metastatic SCCHN;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with cetuximab as compared with cetuximab alone in patients with platinum-resistant, recurrent and/or metastatic SCCHN.


  • Efficacy Parameter [ Time Frame: Overall response rate (ORR)-until the date of first documented progression of such patient's disease or death for 3 years ] [ Designated as safety issue: No ]

    Phase Ib: To determine the MTD/recommended Phase II dose and characterize the pharmacokinetics (PK) of E7050 when administered in combination with cetuximab in patients with platinum-resistant, recurrent and/or metastatic SCCHN;

    Phase II: To evaluate the safety and tolerability of E7050 when administered in combination with cetuximab as compared with cetuximab alone in patients with platinum-resistant, recurrent and/or metastatic SCCHN.



Estimated Enrollment: 95
Study Start Date: May 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active Comparator; Phase IB: Cohort 1,2,and 3

Phase Ib:

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 II: Arm 1; MTD E7050 + 250 mg cetuximab Arm 2; 250 mg cetuximab

Interventions: Drug cetuximab

Drug: E7050
E7050 given orally at 200, 300, or 400 mg once daily.
Active Comparator: Phase II

Phase II:

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

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

Detailed Description:

This open-label, multicenter, randomized study will consist of a Phase Ib: a safety run-in period with 3 ascending doses of E7050 in combination with Cetuximab; and a Phase II portion: a randomized 2-arm period. Approximately 95 patients with Platinum-Resistant Squamous Cell Carcinoma of the head and neck will be enrolled in the study (10-15 patients in the Phase Ib portion and 80 patients in the Phase II portion). Patients will only participate in either the Phase Ib or the Phase II portion of the study.

In the phase II portion, Patients will receive study treatment (E7050 plus Cetuximab or Cetuximab alone) for approximately six 28-day cycles (24 weeks). Beyond 24 weeks, patients 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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;
  • ECOG PS of 0-2;
  • Blood pressure must be well-controlled. Patients must have no history of hypertensive crisis or hypertensive encephalopathy; Adequate end organ function

Exclusion Criteria

  • Nasopharyngeal tumors;
  • Previously received E7050, anti-cmet, anti-angiogenic therapy, or anti-EGFR therapy (prior anti-angiogenic/EGFR therapy is permitted in Phase Ib only. Prior cetuximab is permitted if administered in combination with radiation;
  • Presence of brain metastases, unless the patient 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01332266

Locations
United States, Arizona
Tucson, Arizona, United States, 85715
United States, Florida
Fort Myers, Florida, United States, 33905
United States, Massachusetts
Boston, Massachusetts, United States, 02111
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, Ohio
Toledo, Ohio, United States, 43623
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Nasville, Tennessee, United States, 37203
Korea, Republic of
Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
Hwasun-gun, Jeollanam-do, Korea, Republic of, 519-763
Busan, Korea, Republic of, 602-739
Seoul, Korea, Republic of, 138-736
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 110-744
Seoul, Korea, Republic of, 120-752
Ukraine
Dnipropetrovsk, Ukraine, 49102
Donetsk, Ukraine, 83092
Donetsk, Ukraine, 83003
Kharkiv, Ukraine, 61024
Kyiv, Ukraine, 3057
Sumy, Ukraine, 40005
United Kingdom
London, Greater London, United Kingdom, NW1 2BU
Manchester, Greater Manchester, United Kingdom, M20 4BX
Glasgow, Strathclyde, United Kingdom, G12 0YN
Sponsors and Collaborators
Eisai Inc.
PharmaBio Development Inc.
Investigators
Study Director: Melissa J Versola, RN Innovation Quintiles
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01332266     History of Changes
Other Study ID Numbers: E7050-702, 2011-000773-31
Study First Received: April 7, 2011
Last Updated: July 17, 2014
Health Authority: Ukraine: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Cancer
head and neck
squamous cell carcinoma of the head and neck
phase I
phase II

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Cetuximab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014