An Open-Label Study of E7974 Administered on Days 1, 8, and 15 of a 28-Day Cycle and Days 1 and 8 of a 21-Day Cycle in Patients With Solid Malignancies

This study has been completed.
Sponsor:
Information provided by:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00121732
First received: July 15, 2005
Last updated: November 10, 2009
Last verified: November 2009
  Purpose

The purpose of this study is to determine the maximum tolerated dose (MTD) of E7974 administered as an intravenous bolus dose on Days 1, 8, and 15 of a 28-day cycle (Arm A) or on Days 1 and 8 of a 21-day cycle (Arm B) to patients with solid tumors that have progressed following effective therapy or for which no effective therapy exists.


Condition Intervention Phase
Solid Tumor Malignancies, Cancer
Drug: E7974
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Two-Arm, Open-Label Study of E7974 Administered on Days 1, 8, and 15 of a 28-Day Cycle and Days 1 and 8 of a 21-Day Cycle in Patients With Solid Malignancies

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Determine the maximum tolerated dose of E7974 in patients with solid malignancies. [ Time Frame: Duration of each cycle will be 28 or 21 days; patients will attend a follow-up visit 30 days after last study treatment. Follow-up for safety and efficacy will occur 6 months after the last patient is accrued to the study. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1) Assess E7974 for safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD); 2) Evaluate the correlation of AUC with clinical toxicity and efficacy in both arms. [ Time Frame: Duration of each cycle will be 28 or 21 days; patients will attend a follow-up visit 30 days after last study treatment. Follow-up for safety and efficacy will occur 6 months after the last patient is accrued to the study. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: July 2005
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: E7974
Maximum tolerated dose = 0.15 mg/m^2 administered on Days 1, 8, 15 of 28-day cycle.
Experimental: B Drug: E7974
Maximum tolerated dose = 0.37 mg/m^2 administered on Days 1 and 8 of 21-day cycle.

Detailed Description:

This is a two-arm, open-label, non-randomized, dose-escalation study to determine the MTD of E7974 administered as an intravenous bolus dose on Days 1, 8, and 15 of a 28-day cycle (Arm A) or on Days 1 and 8 of a 21-day cycle (Arm B) to patients with solid tumors that have progressed following effective therapy or for which no effective therapy exists. Response and progression will be evaluated in this study using Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients who meet all of the inclusion criteria and none of the exclusion criteria will be eligible for entry into the study:

  1. Patients must have a pathologically diagnosed, histologically or cytologically confirmed solid tumor that has progressed following effective therapy or for which no effective therapy exists (including surgery or radiation therapy).
  2. Patients must be >= 18 years of age.
  3. Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
  4. Patients must have a life expectancy of >= 3 months.
  5. Patients must have adequate renal function as evidenced by serum creatinine <= 1.5 mg/dL or creatinine clearance >= 40 mL/minute (min).
  6. Patients must have adequate bone marrow function as evidenced by absolute neutrophil count >= 1,500/µL, hemoglobin of >= 9 g/dL (may be transfused), and platelet count (not transfused) >= 100,000/µL.
  7. Patients must have adequate liver function as evidenced by bilirubin <= 1.5 mg/dL and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3 times the upper limits of normal (ULN), unless related to liver involvement by tumor, in which case <= 5.0 times ULN.
  8. Patients must be willing and able to sign written informed consent and be able to comply with the study protocol for the duration of the study.
  9. Patients must be willing and able to undergo blood draw and urine sampling for PK in Cycle 1.
  10. Patients may have either measurable or non-measurable disease.

Exclusion Criteria:

The presence of one or more of the following criteria will disqualify a patient from enrollment in the study:

  1. Patients who have received chemotherapy within three weeks of E7974 treatment start (6 weeks for a nitrosourea).
  2. Patients who have not recovered from any chemotherapy-related or other therapy-related toxicity to <= Grade 1 at study entry (excluding Grade 2 alopecia).
  3. Patients who have received radiotherapy <= 3 weeks prior to study enrollment, whose marrow exposure has exceeded 25% and who have not recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia).
  4. Patients who have had major surgery without full recovery or major surgery within three weeks of E7974 treatment start.
  5. Patients with primary brain tumors or metastasis at study entry must have controlled them for >= 1 month by previous treatment, including radiation therapy and corticosteroids.
  6. Women who are pregnant or breastfeeding.
  7. Women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test.
  8. Women of childbearing potential unless (1) surgically sterile, (2) physiologically postmenopausal for > 12 months, or (3) using adequate measures (including barrier methods) of contraception.
  9. Fertile men or their partners who are not willing to use contraception.
  10. Patients who have a positive history for Human Immunodeficiency Virus (HIV) and/or have active hepatitis B or active hepatitis C at study entry.
  11. Patients with severe, uncontrolled intercurrent illness or infection.
  12. Patients with medically uncontrolled cardiovascular illness defined as unstable angina, >= symptomatic Grade II New York Heart Association (NYHA) Classification congestive heart failure (CHF), or myocardial infarction within six months prior to study entry.
  13. Patients who have received organ allografts requiring immunosuppressive therapy.
  14. Patients who have received investigational drugs including immunotherapy, gene therapy, hormone therapy, biologic therapy, or chemotherapy within the three-week period prior to E7974 treatment start; patients must have recovered from any previous major therapy-related toxicities (Grade 3 or 4) to <= Grade 1 at study entry.
  15. Patients with a current history of peripheral neuropathy > CTC Grade 2 (e.g., diabetic or chemotherapy-induced neuropathy).
  16. Patients with a history of uncontrolled seizures.
  17. Patients with marked baseline prolongation of QT/QTc interval (QTc interval >470) using the Fridericia method as the main method of QTc analysis.
  18. Patients with other significant diseases or disorders that, in the Investigator's opinion, would exclude them from the study.
  19. Patients with allergy or hypersensitivity to hemiasterlin based product or analogue.
  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: NCT00121732

Locations
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Texas
CTRC
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Jenny Zhang, M.D. Eisai Inc.
  More Information

No publications provided

Responsible Party: Peter Tarassoff, MD, Eisai Medical Research Inc.
ClinicalTrials.gov Identifier: NCT00121732     History of Changes
Other Study ID Numbers: E7974-A001-101
Study First Received: July 15, 2005
Last Updated: November 10, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 28, 2014