Study of E7389 Administered Once Every 3 Weeks In Patients With Advanced Solid Tumors

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00069277
• Collaborator: (none)
• Enrollment: 21
• Locations: 3
• Duration (Months): 20
• Patients Per Site: 7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The malignancies (advanced solid tumors) that have been chosen for evaluation of E7389 are those where E7389 has demonstrated significant pre-clinical anti-tumor activity, both in vitro and in vivo. The ultimate goal is to demonstrate the clinical activity of E7389 in the treatment of these, and potentially other, tumor types.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: E7389	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Dose-Finding Study of E7389 (Halichondrin B Analog) Administered Once Every Three Weeks in Patients With Advanced Solid Tumors
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Apr 1, 2005
• Actual Study Completion Date: Apr 1, 2005

Outcome Measures

Primary Outcome Measures

1. Response and Progression Will be Evaluated in This Study Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in Only the Largest Diameter of the Tumor Lesions Are Used. [12 Weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have a histologically or cytologically confirmed and measurable advanced solid tumor that has progressed following standard therapy or for which no standard therapy exists (including surgery or radiation therapy)

• Patients may have received prior chemotherapy (limit of two prior chemotherapy regimens)

• Patients must be aged >= 18 years

• Patients must have a Karnofsky Performance Status of > 70% -- Patients must have a life expectancy of > 3 months

• Patients must have adequate renal function as evidenced by serum creatinine <1.5 mg/dL or creatinine clearance > 60 mL/minute

• Patients must have adequate bone marrow function as evidenced by absolute neutrophil count > 1,500/µL and platelets > 100,000/µL

• Patients must have adequate liver function as evidenced by bilirubin < 1.5 mg/dL and alanine transaminase (ALAT) and aspartate transaminase (ASAT) < 2 times the upper limits of normal

• Patients must be willing and able to comply with the study protocol for the duration of the study

• Patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

Exclusion Criteria:

• Patients who have received chemotherapy within three weeks (six weeks if nitrosoureas were received) of E7389 treatment start

• Patients who have not recovered from any chemotherapy related or other therapy related toxicity at study entry

• Patients who require therapeutic doses of anti-coagulant therapy (eg, Coumadin, heparin, low molecular weight heparin). Low doses of anticoagulants used for patency (e.g., lines, catheters, ports) are permitted.

• Women who are pregnant or breastfeeding.

• 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 (postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential)

• Fertile men who are not willing to use contraception or fertile men with a female partner who is not willing to use contraception

• Patients who have not successfully completed local therapy for previously treated central nervous system (CNS) metastases and who have not been discontinued from corticosteroids for at least four weeks before starting treatment with E7389. Patients with asymptomatic brain metastases who have no evidence of midline shift on CT scan or MRI 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.

• Patients who have tested positive for HIV

• Patients with severe uncontrolled intercurrent illness/infection (excluding malignancies)

• Patients with cardiovascular impairment

• Patients with organ allografts

• Patients who have received investigational drugs, including immunotherapy, gene therapy, hormone therapy, or other biologic therapy; anti-neoplastic therapy; or radiation therapy (other than required for palliation) within three weeks of E7389 treatment start

• Patients who have had major surgery within four weeks of E7389 treatment start without a full recovery

• Patients with a hypersensitivity to Halichondrin B and/or Halichondrin B-like compounds Patients with other significant disease that, in the Investigator's opinion, would exclude the patient from the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Institute Medical Group	Los Angeles	California	United States	90025
2	Premiere Oncology	Santa Monica	California	United States	90404
3		New Brunswick	New Jersey	United States	08901

Sponsors and Collaborators

• Eisai Inc.

Investigators

• Study Director: Dale Schuster, Ph.D, Eisai Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00069277
• Other Study ID Numbers: E7389-A001-102
• First Posted: Sep 24, 2003
• Last Update Posted: Apr 11, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by , ,: Cancer, tumors

Study Results

Participant Flow

Recruitment Details	This study was recruited at 2 centers in U.S.during the period of Aug 2003 to Apr 2005.

Arm/Group Title	E7389 Dose-Escalating
Arm/Group Description	E7389 dose-escalation starting at 0.25 mg/m^2 intravenous on Day 1 of a 21 day cycle. Dose escalations scheme used a two part design and proceeded based on dose-limiting toxicity and maximum tolerated dose.
Period Title: Overall Study
STARTED	21
COMPLETED	0
NOT COMPLETED	21

Baseline Characteristics

Arm/Group Title	E7389 Dose-Escalating
Arm/Group Description	E7389 dose-escalation starting at 0.25 mg/m^2 intravenous on Day 1 of a 21 day cycle. Dose escalations scheme used a two part design and proceeded based on dose-limiting toxicity and maximum tolerated dose.
Overall Participants	21
Age, Customized (participants) [Mean (Standard Deviation) ]
Mean (+/- Standard Deviation)	59.0 (11.2) 281%
Sex: Female, Male (Count of Participants)
Female	8 38.1%
Male	13 61.9%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 9.5%
White	16 76.2%
More than one race	0 0%
Unknown or Not Reported	0 0%
Hispanic/Latino	3 14.3%

Outcome Measures

1. Primary Outcome

Title	Response and Progression Will be Evaluated in This Study Using the New International Criteria Proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in Only the Largest Diameter of the Tumor Lesions Are Used.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	E7389 Dose-Escalating
Arm/Group Description	E7389 dose-escalation starting at 0.25 mg/m^2 intravenous on Day 1 of a 21 day cycle. Dose escalations scheme used a two part design and proceeded based on dose-limiting toxicity and maximum tolerated dose.
Measure Participants	21
partial response	1 4.8%
stable disease	12 57.1%
progressive Disease	7 33.3%

Adverse Events

Arm/Group Title	E7389 Dose-Escalating
Arm/Group Description	E7389 dose-escalation starting at 0.25 mg/m^2 intravenous on Day 1 of a 21 day cycle. Dose escalations scheme used a two part design and proceeded based on dose-limiting toxicity and maximum tolerated dose.
All Cause Mortality
	E7389 Dose-Escalating
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	E7389 Dose-Escalating
	Affected / at Risk (%)	# Events
Total	10/21 (47.6%)
Blood and lymphatic system disorders
Febrile Neutropenia	6/21 (28.6%)
Cardiac disorders
Myocardial Infarction	1/21 (4.8%)
Gastrointestinal disorders
Ileus	1/21 (4.8%)
Diarrhea	1/21 (4.8%)
Dysphagia	1/21 (4.8%)
General disorders
Pyrexia	1/21 (4.8%)
Fatigue	1/21 (4.8%)
Infections and infestations
Infection	1/21 (4.8%)
Pneumonia	1/21 (4.8%)
Bacteremia	1/21 (4.8%)
Cellulitis	1/21 (4.8%)
Investigations
Hyponatremia	1/21 (4.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Central Nervous System	2/21 (9.5%)
Nervous system disorders
Headache	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	E7389 Dose-Escalating
	Affected / at Risk (%)	# Events
Total	20/21 (95.2%)
Blood and lymphatic system disorders
Anemia	6/21 (28.6%)
Febrile Neutropenia	6/21 (28.6%)
Leukopenia	4/21 (19%)
Neutropenia	8/21 (38.1%)
Thrombocytopenia	2/21 (9.5%)
Cardiac disorders
Tachycardia	2/21 (9.5%)
Gastrointestinal disorders
Abdominal Distention	2/21 (9.5%)
Abdominal Pain	3/21 (14.3%)
Abdominal Pain Upper	2/21 (9.5%)
Constipation	6/21 (28.6%)
Diarrhea	3/21 (14.3%)
Dry Mouth	2/21 (9.5%)
Gastroesophageal Reflux Disease	2/21 (9.5%)
Nausea	5/21 (23.8%)
Vomiting	2/21 (9.5%)
General disorders
Chest Pain	3/21 (14.3%)
Fatigue	11/21 (52.4%)
Mucosal Inflammation	2/21 (9.5%)
Peripheral Edema	3/21 (14.3%)
Pyrexia	3/21 (14.3%)
Infections and infestations
Oral Candidiasis	2/21 (9.5%)
Upper Respiratory Tract Infection	2/21 (9.5%)
Urinary Tract Infection	2/21 (9.5%)
Investigations
Alanine Aminotransferase Increased	3/21 (14.3%)
Blood Alkaline Phosphatase Increased	2/21 (9.5%)
Weight Decreased	4/21 (19%)
White Blood Cell Count Decreased	2/21 (9.5%)
Metabolism and nutrition disorders
Anorexia	4/21 (19%)
Decreased Appetite	4/21 (19%)
Hyperglycemia	2/21 (9.5%)
Hyponatremia	2/21 (9.5%)
Musculoskeletal and connective tissue disorders
Back Pain	5/21 (23.8%)
Chest Wall Pain	2/21 (9.5%)
Myalgia	4/21 (19%)
Pain in Extremity	3/21 (14.3%)
Nervous system disorders
Dizziness	4/21 (19%)
Headache	3/21 (14.3%)
Psychiatric disorders
Insomnia	3/21 (14.3%)
Renal and urinary disorders
Dysuria	3/21 (14.3%)
Respiratory, thoracic and mediastinal disorders
Cough	4/21 (19%)
Dyspnea	2/21 (9.5%)
Dyspnea Exertional	2/21 (9.5%)
Nasal Congestion	2/21 (9.5%)
Rhonchi	2/21 (9.5%)
Wheezing	2/21 (9.5%)
Skin and subcutaneous tissue disorders
Alopecia	7/21 (33.3%)
Dry Skin	3/21 (14.3%)
Hyperhidrosis	2/21 (9.5%)
Night Sweats	3/21 (14.3%)
Pruritis	4/21 (19%)
Rash Pruritic	2/21 (9.5%)
Vascular disorders
Hypotension	2/21 (9.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.