A Dose-Finding 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

The purpose of this study is to determine the maximum tolerated dose (MTD) of E7050 given orally in patients with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: E7050

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital
  • Surrey, United Kingdom, SM2 5PT
    • Royal Marsden Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years.
2. Histologically and/or cytologically confirmed metastatic solid tumors, that have progressed after treatment with approved therapies, or for which there are no standard effective therapies available.
3. Adequate bone marrow function.
4. Adequate renal function.
5. Adequate liver function.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
7. Life expectancy > 3 months.

8. Be willing and able to comply with the study protocol, and can give written informed consent.

   Additional inclusion criterion for the additional 15 patients recruited to the expanded MTD cohort only:

9. At least one tumor lesion with diameter >= 2 cm measurable according to Modified RECIST.

Exclusion Criteria:

1. Any condition that may preclude oral intake or oral absorption, history of gastrointestinal malabsorption, or surgery involving gastro- and/or intestinal- anastomosis within 4 weeks prior to starting study drug.
2. Untreated or unstable known primary or metastatic central nervous system (CNS) tumors (stability shown by contrast-enhanced computed tomography or magnetic resonance imaging scans at least 8 weeks apart, with the most recent scan obtained within 28 days prior to starting study treatment).
3. Known human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infection or intercurrent illness (unrelated to tumor).
4. Prior surgery, radiotherapy, chemotherapy, biologic therapy or investigational drugs within 4 weeks prior to starting study drug. Prior immunotherapy, hormonal, or molecular targeted therapy within 2 weeks prior to starting study treatment (except gonadorelin analogue therapy for prostate cancer is allowed). (All acute toxicities related to prior treatments should have resolved).
5. Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within 6 months prior to starting study drug.
6. Requiring therapeutic anti-coagulant therapy (prophylactic dose of heparin or low molecular weight heparin is allowed).
7. Poorly controlled hypertension (defined as a change in hypertensive therapy within 3 months of starting study drug) or hypertension diagnosed at screening (defined as a repeat blood pressure measurement of 160/90 mmHg or higher).

8. Pregnancy or lactation. Female patients of childbearing potential must have a negative pregnancy test before inclusion into the study, and must agree to use medically acceptable methods of contraception (e.g. abstinence, or a double-barrier method [e.g. condom + spermicide, condom + diaphragm with spermicide], or IUD, or have a vasectomised partner) starting at Screening and throughout the entire study period and for 2 months after the last dose of study drug. Those female patients using hormonal contraceptives must also be using an additional approved method of contraception (as described previously) starting at Cycle 1 Day 1, and continuing throughout the entire study period and for 2 months after the last dose of study drug.

   Perimenopausal women must have been amenorrheic for at least 12 months; otherwise a pregnancy test is required.

   Male patients must agree to use contraceptive methods (e.g., abstinence, or a double-barrier method [e.g., condom + spermicide, condom + partner diaphragm with spermicide]).

   Additional exclusion criterion for the additional 15 patients recruited to the expanded MTD cohort only:

9. History of any malignancy other than the present malignancy (except treated non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off all therapy for that disease for a minimum of 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: E7050; Oral dosing starting at 100 mg once daily. After the MTD of once daily dosing has been determined, subsequent cohorts will be treated with a divided dosing schedule either twice or three times daily. The starting dose for this schedule will be an appropriate level below the MTD for once daily dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose: the highest dose at which no more than 1 out of 6 patients experiences Dose Limiting Toxicity (DLT) during Cycle 1.	Weekly assessments during the first 4 weeks of treatment.

Secondary Outcome Measures

Outcome Measure	Time Frame
DLTs and adverse events.	Weekly assessments during the first 4 weeks of treatment for DLTs and throughout the study for AEs.
Pharmacokinetics (blood and urine).	Weekly assessments of blood during Cycle 1 and every 2 weeks for subsequent cycles and of urine on Day 1 of Cycles 1 and 2.
Pharmacodynamics (blood).	Weekly assessments during Cycle 1, every 2 weeks on Cycle 2, and on Day 1 of subsequent cycles.
Best overall tumor response, duration of response and duration of stable disease assessed according to modified RECIST (Response Evaluation Criteria in Solid Tumors).	At Screening, between Days 21 and 28 of every even cycle, and at the Final Visit.

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: Wouter Hanekom, Eisai Limited

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: March 25, 2009
• First Submitted That Met QC Criteria: March 25, 2009
• First Posted (Estimate): March 26, 2009

Study Record Updates

• Last Update Posted (Estimate): January 29, 2016
• Last Update Submitted That Met QC Criteria: January 27, 2016
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Advanced solid tumors
• Other Study ID Numbers: E7050-E044-101