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A Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors
This study is currently recruiting participants.
Verified by Eisai Inc., August 2009
First Received: December 21, 2005   Last Updated: September 1, 2009   History of Changes
Sponsored by: Eisai Inc.
Information provided by: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00268905
  Purpose

The purpose of this study is to determine the maximum tolerated dose (MTD) and to explore the safety and anti-tumor activity of E7389 in combination with carboplatin in patients with advanced solid tumors.


Condition Intervention Phase
Cancer
Drug: E7389 + carboplatin AUC 5
Drug: E7389 + carboplatin AUC 6
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety Study
Official Title: A Phase Ib Open-Label, Two-Arm, Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Efficacy will be determined by best overall objective tumor response rate as defined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria, overall survival, progression free survival & duration of response. [ Time Frame: Tumor response: once every second cycle or sooner if disease progression occurs, or once every third cycle if patients remain in the study beyond 12 months. Survival will be recorded from the start of E7389 until disease progression or death. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety will be assessed by adverse events (AE), dose limiting toxicities (DLT), and laboratory parameters. Other assessments will include pharmacokinetics (PK). [ Time Frame: AEs, DLTs, and laboratory measurements assessed on Days 1, 8, and 15 of each cycle. AEs and labs also assessed within 30 days after discontinuation. PK samples on Days 1, 2 and 3 of Cycle 1. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 85
Study Start Date: October 2006
Estimated Study Completion Date: November 2010
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental Drug: E7389 + carboplatin AUC 5
Patients will receive E7389 before (Schedule A) or after (Schedule B) carboplatin AUC 5 infusion. E7389 will be administered as a 2-5 minute intravenous (IV) bolus infusion at a starting dose of 0.7 mg/m^2 on Days 1 and 8 every 21 days. Carboplatin 5 AUC will be administered as a 30-minute IV infusion on Day 1 every 21 days. Dose escalation will be performed in cohorts of three patients per dose level per schedule.
2: Experimental Drug: E7389 + carboplatin AUC 6
After MTD is reached with carboplatin AUC 5, dose escalation of E7389 in combination with carboplatin at AUC 6 will begin at one dose level below MTD, using the preferred schedule (A or B). If carboplatin AUC 6 with E7389 is tolerated, the MTD reached will be used to enroll 20 additional patients with Stage IIIB or IV non-small cell lung cancer (NSCLC). If carboplatin AUC 6 is not tolerated, these patients will be enrolled at the MTD determined with the combination of E7389 and carboplatin AUC 5.

Detailed Description:

This is a Phase Ib open-label, two-arm, dose-finding study of E7389 in combination with carboplatin in patients with solid tumors.

  Eligibility

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

Inclusion Criteria:

  1. Patients ≥ 18 years of age.
  2. Patients with an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
  3. Patients with a life expectancy of ≥ three months.
  4. Patients with adequate renal function as evidenced by serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula.
  5. Patients with adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, hemoglobin ≥ 10.0 g/dL (this may have been corrected by transfusion or growth factors) and platelet count ≥ 100

    • 10^9/L.
  6. Patients with adequate liver function as evidenced by bilirubin ≤ 1.5 mg/dL and alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limits of normal (ULN) (in the case of liver metastases ≤ 5 x ULN), unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase. to assess the liver function instead of the total alkaline phosphatase.
  7. Patients willing and able to comply with the study protocol for the duration of the study.
  8. Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

For patients in the dose finding phase, the following additional inclusion criteria must be fulfilled:

  1. Patients with pathologically diagnosed, histologically or cytologically confirmed advanced solid tumor, that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy).
  2. Patients with disease progression despite standard therapy or have disease for which no standard therapy exists.
  3. Patients with ≤ Grade 2 chemotherapy or radiation-related toxicities except alopecia.

For NSCLC patients at the MTD, the following additional inclusion criteria must be fulfilled:

  1. Patients with pathologically diagnosed, histologically or cytologically confirmed advanced NSCLC (Stage IIIB or IV) with measurable disease, not amenable to surgical or radiation treatment.
  2. Patients with no prior chemotherapy for disease, including neoadjuvant or adjuvant treatment.

Exclusion Criteria:

  1. Patients who have received investigational drugs, including immunotherapy, gene therapy, hormone therapy (except Leuprolide and megestrol acetate for appetite stimulation), or other biological therapy; conventional chemotherapy; radiation; or hormonal therapy within three weeks; major surgery without full recovery or major surgery within 3 weeks of starting on this study; patients must have recovered from any previous major therapy related toxicity (Grade 3 or 4) to < Grade 2 at study entry.
  2. Patients who have received radiation ≤ 3 weeks prior to study enrollment, whose marrow exposure has exceeded 30% or who have not recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia).
  3. Patients who have received prior high dose chemotherapy with hematopoietic stem cell rescue or stem cell or bone marrow transplant in the past two years.
  4. Patients with pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
  5. Patients with active symptomatic brain metastases. Patients with central nervous system (CNS) metastases are considered eligible if they have had adequately treated brain metastases, ie, have completed treatment (tapered off steroids) at least four weeks before starting treatment with E7389. Patients who have no evidence that the metastases are symptomatic or actively growing (no evidence of midline shift on computed tomography scan or magnetic resonance imaging) may be enrolled without initiation of local therapy for the CNS metastases. In this case, a repeat scan must be performed within four weeks of the original scan to ensure that disease progression is not occurring. It is not the intention of this study to treat patients with active brain metastases.
  6. Patients with meningeal carcinomatosis.
  7. Patients who require therapeutic anti-coagulant therapy with warfarin or related compounds.
  8. Women who are pregnant or breast-feeding. Women of childbearing potential with either a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the investigator (e.g., using 2 forms of contraception including a barrier method). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  9. Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception.
  10. Patients with severe/uncontrolled intercurrent illness or infection.
  11. Patients with significant cardiovascular impairment (history of congestive heart failure > New York Heart Association Grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).
  12. Patients with organ allografts.
  13. Patients who have a history of positive testing for HIV and/or have active hepatitis B or active hepatitis C at study entry.
  14. Patients with pre-existing neuropathy > Grade 2.
  15. Patients with a hypersensitivity to halichondrin B and/or to a halichondrin B chemical derivative.
  16. Patients who participated in a prior E7389 clinical trial.
  17. Patients with other significant disease or disorders that, in the investigator's opinion, would exclude the patient from the study.

For NSCLC patients at the MTD, the following additional exclusion criterion must be fulfilled:

1. Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated ≥ five years previously with no subsequent evidence of recurrence.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00268905

Contacts
Contact: Eisai Medical Services 1-888-422-4743

Locations
United States, New Jersey
Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States
Albert Einstein Cancer Center Recruiting
Bronx, New York, United States
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Dale Shuster, Ph.D Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Medical Research Inc. ( Dale Shuster, Ph.D )
Study ID Numbers: E7389-A001-104
Study First Received: December 21, 2005
Last Updated: September 1, 2009
ClinicalTrials.gov Identifier: NCT00268905     History of Changes
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Signs and Symptoms
Carboplatin

Additional relevant MeSH terms:
Antineoplastic Agents
Therapeutic Uses
Carboplatin
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 10, 2009