Evaluating E7389 in Patients With Hormone Refractory Prostate Cancer With Advanced and/or Metastatic Disease Stratified by Prior Chemotherapy

• Sponsor: Eisai Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00278993
• Collaborator: (none)
• Enrollment: 108
• Locations: 18
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a multi-centre, phase II, open-label, two-stage design, single-arm study in patients with hormone-refractory prostate cancer (HRPC) with advanced (rising PSA) and/or metastatic disease and who have had prior anti-androgen therapy. The study will further explore the efficacy of E7389 by enrollment of patients into two strata: those who have had no prior systemic chemotherapy for their disease (except for mitoxantrone and estramustine), and those who failed no more than one previous chemotherapeutic regimen with tubulin-binding agents such as docetaxel.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: E7389	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicenter, Open Label, Two Stage Design Study Evaluating E7389 in Patients With Hormone Refractory Prostate Cancer With Advanced and/or Metastatic Disease Stratified by Prior Chemotherapy
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 With stratification	Drug: E7389; Intravenous 1.4 mg/m2 on a 3-week course.

Outcome Measures

Primary Outcome Measures

1. Objective Prostate Specific Antigen (PSA) Response Rate Based on Bubley Criteria [12 months]

   Bubley Criteria: Patients must have progressive disease to enter study. For outcomes, PSA response must show at least 50% decrease. Duration of response is the time from >50% decrease from baseline to when there is a 50% decrease in nadir. PSA progressive disease- 25% increase from baseline or increase of 5 ng/mL along with measureable disease Stable disease- decline of less than 50% and not more than 25% increase.

Secondary Outcome Measures

1. Duration of Prostate Specific Antigen Response Based on Bubley Criteria [12 months.]

   Duration of response is the time from >50% decrease from baseline to when there is a 50% decrease in nadir.

2. Progression Free Survival [12 months]

   From the date study treatment was initiated until the earliest date of the first PSA assessment that determined progressive disease, or the death of death if death occurred without disease progression.

3. Overall Survival [12 months]

4. Best Objective Tumor Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria [12 months]

   Based on Response Evaluation Criteria in Solid Tumors (RECIST), consisting of complete response (CR) plus partial response (PR). Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).

Eligibility Criteria

Criteria

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

Inclusion criteria:

1. Males with histologically proven adenocarcinoma of the prostate that has progressed (ie. a minimum of 3 consecutive rises in Prostate Specific Antigen (PSA) (with the last value ≥ 4 ng/mL) taken at least 1 week apart prior to study entry) despite castration or maintenance of castrate-level testosterone (defined as serum testosterone ≤ .50 ng/dL or 1.7 nmol/L), or progressed during non-hormonal chemotherapy.

Note: Patients previously treated with an antiandrogen must have disease progression documented after antiandrogen withdrawal. Those who have not undergone orchiectomy must continue medical castration with a gonadotropin-releasing hormone analog. At least 4 weeks must have elapsed between the withdrawal of antiandrogens (6 weeks in the case of nilutamide or bicalutamide and four weeks in the case of flutamide or other secondary hormonal therapy) and enrollment, so as to avoid the possibility of confounding results of the response due to antiandrogen withdrawal.

1. Patients must fulfill one of the following two criteria to be stratified:

• No prior chemotherapy (except mitoxantrone or estramustine) for advanced and/or metastatic disease as defined in inclusion criteria #1.

• Failure of no more than one previous chemotherapeutic regimen with tubulin binding agents such as docetaxel.

1. Resolution of all chemotherapy or radiation-related toxicities to less than grade 2 severity, except neuropathy and alopecia

2. Age ≥ 18 years.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

4. Life expectancy of ≥ 3 months.

5. Adequate renal function as evidenced by serum creatinine ≤ 1.5 times upper limits of normal (ULN) or calculated creatinine clearance ≥ 40 mL/minute (min) per the Cockcroft and Gault formula.

6. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) ≥ 1.5 x 10^{9/L, hemoglobin ≥ 9.0 g/dL (or 5.5 mmol/L), and platelet count ≥ 100 x 10}9/L. Adequate liver function as evidenced by bilirubin ≤ 1.5 x ULN, alanine transaminase (ALT), and aspartate transaminase (AST) ≤ 3 x ULN (in the case of liver metastases ≤ 5 x ULN).

7. Patients willing and able to complete the VAS (Visual Analog Scale).

8. Patients willing and able to comply with the study protocol for the duration of the study.

9. 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:

1. Patients who have received chemotherapy, radiation, or experimental therapy within 4 weeks of start of E7389 treatment

2. Radiation therapy encompassing ≥30% of marrow or treatment with radioactive strontium

3. Patients who require therapeutic anti-coagulant therapy with warfarin or related compounds; (mini dose warfarin or related compounds are permitted).

4. Severe / uncontrolled intercurrent illness/infection.

5. Significant cardiovascular impairment (history of congestive heart failure > NYHA grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia)

6. Patients with organ allografts.

7. Patients with known immunosuppression such as positive HIV status.

8. Patients who have had a prior malignancy, other than nonmelanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated ≥ 5 years previously with no subsequent evidence of recurrence.

9. Patients with pre-existing neuropathy > Grade 2

10. Patients with brain or subdural metastases are not eligible, except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least two weeks before starting treatment with E7389.

11. Patients with meningeal carcinomatosis.

12. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.

13. Patients who participated in a prior E7389 clinical trial.

14. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dr. Robert Jotte	Denver	Colorado	United States	80218
2	Melbourne Internal Medicine Associates	Melbourne	Florida	United States	32901
3	Ocala Oncology Center PL	Ocala	Florida	United States	34474
4	Central Indiana Cancer Centers	Indianapolis	Indiana	United States	46227
5	Minnesota Hematology Oncology	Burnsville	Minnesota	United States	33557
6	Missouri Cancer Associates	Columbia	Missouri	United States	65201
7	New York Oncology Hematology, P.C.	Albany	New York	United States	12208
8	St. Luke's Roosevelt Hospital Center	New York	New York	United States	10019
9	Columbia University Medical Center	New York	New York	United States	10032
10	Raleigh Hematology Oncology Associates PL	Raleigh	North Carolina	United States	27607
11	US Oncology	Dallas	Texas	United States	75204
12	Mary Crowley Medical Research Center	Dallas	Texas	United States	75246
13	El Paso Cancer Treatment Center	El Paso	Texas	United States	79915
14	Texas Oncology PA	Fort Worth	Texas	United States	76104
15	Texas Oncology PA	Tyler	Texas	United States	75702
16	Tyler Cancer Center	Tyler	Texas	United States	75702
17	Deke Slayton Cancer Center	Webster	Texas	United States	77598
18	Virginia Oncology Associates	Norfolk	Virginia	United States	23505

Sponsors and Collaborators

• Eisai Inc.

Investigators

• Study Director: Asha Das, Eisai Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT00278993
• Other Study ID Numbers: E7389-G000-204; 2005-004271-37
• First Posted: Jan 19, 2006
• Last Update Posted: Jul 14, 2014
• Last Verified: Apr 1, 2012

• Keywords provided by Eisai Inc.: Prostate cancer; metastatic disease
• Additional relevant MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis

Study Results

Participant Flow

Recruitment Details	This study was recruited at 22 centers in U.S, UK, Spain and Hungary during the period of Feb 2006 to May 2009.

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
Period Title: Overall Study
STARTED	108
COMPLETED	1
NOT COMPLETED	107

Baseline Characteristics

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
Overall Participants	108
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.0 (9.36)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	108 100%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	0 0%
Asian	3 2.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 5.6%
White	94 87%
More than one race	0 0%
Other	5 4.6%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Objective Prostate Specific Antigen (PSA) Response Rate Based on Bubley Criteria
Description	Bubley Criteria: Patients must have progressive disease to enter study. For outcomes, PSA response must show at least 50% decrease. Duration of response is the time from >50% decrease from baseline to when there is a 50% decrease in nadir. PSA progressive disease- 25% increase from baseline or increase of 5 ng/mL along with measureable disease Stable disease- decline of less than 50% and not more than 25% increase.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
Measure Participants	105
Response	16.2 15%
Stable Disease	52.4 48.5%
Progressive Disease	29.5 27.3%
Unknown/Not Evaluated	1.9 1.8%

2. Secondary Outcome

Title	Duration of Prostate Specific Antigen Response Based on Bubley Criteria
Description	Duration of response is the time from >50% decrease from baseline to when there is a 50% decrease in nadir.
Time Frame	12 months.

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
Measure Participants	105
Median (Full Range) [Days]	96

3. Secondary Outcome

Title	Progression Free Survival
Description	From the date study treatment was initiated until the earliest date of the first PSA assessment that determined progressive disease, or the death of death if death occurred without disease progression.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
Measure Participants	105
Median (Full Range) [Days]	64

4. Secondary Outcome

Title	Overall Survival
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Intent to Treat Population

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
Measure Participants	108
Median (Full Range) [Days]	567

5. Secondary Outcome

Title	Best Objective Tumor Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Description	Based on Response Evaluation Criteria in Solid Tumors (RECIST), consisting of complete response (CR) plus partial response (PR). Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per Protocol Population

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
Measure Participants	105
Patients with measureable tumors	59 54.6%
Complete Response	0 0%
Partial Response	8.1 7.5%
Stable Disease	72.6 67.2%
Progressive Disease	8.1 7.5%
Unknown	11.3 10.5%

Adverse Events

Arm/Group Title	E7389 Intravenous 1.4 mg/m2
Arm/Group Description	E7389 intravenous 1.4 mg/m2 on a 3-week course
All Cause Mortality
	E7389 Intravenous 1.4 mg/m2
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	E7389 Intravenous 1.4 mg/m2
	Affected / at Risk (%)	# Events
Total	34/108 (31.5%)
Blood and lymphatic system disorders
Anemia	2/108 (1.9%)
Febrile Neutropenia	3/108 (2.8%)
Neutropenia	2/108 (1.9%)
Abdominal Pain	1/108 (0.9%)
Diarrhea	2/108 (1.9%)
Cardiac disorders
Bradycardia	2/108 (1.9%)
Cardiac Arrest	3/108 (2.8%)
Tachycardia	2/108 (1.9%)
Gastrointestinal disorders
Gastrointestinal Hemorrhage	1/108 (0.9%)
Intestinal Obstruction	1/108 (0.9%)
Melena	2/108 (1.9%)
Esophageal Ulcer Hemorrhage	1/108 (0.9%)
General disorders
Chest Pain	1/108 (0.9%)
Edema Peripheral	1/108 (0.9%)
Pyrexia	3/108 (2.8%)
Suprpubic Pain	1/108 (0.9%)
Infections and infestations
Pharyngitis Streptococcal	1/108 (0.9%)
Pneumonia	4/108 (3.7%)
Sepsis	1/108 (0.9%)
Urinary Tract Infection	2/108 (1.9%)
Uriosepsis	3/108 (2.8%)
Metabolism and nutrition disorders
Dehydration	3/108 (2.8%)
Hyperglycemia	1/108 (0.9%)
Hypocalcemia	1/108 (0.9%)
Hyponatremia	1/108 (0.9%)
Hypovolemia	1/108 (0.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/108 (0.9%)
Muscular Weakness	1/108 (0.9%)
Pathological Fracture	1/108 (0.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Neoplasm Progression	2/108 (1.9%)
Nervous system disorders
Hemiparesis	1/108 (0.9%)
Spinal Cord Compression	3/108 (2.8%)
Psychiatric disorders
Confusional State	1/108 (0.9%)
Renal and urinary disorders
Bladder Obstruction	1/108 (0.9%)
Hematuria	1/108 (0.9%)
Renal Colic	1/108 (0.9%)
Renal Failure	4/108 (3.7%)
Renal Failure Acute	1/108 (0.9%)
Reproductive system and breast disorders
Prostatic Pain	1/108 (0.9%)
Respiratory, thoracic and mediastinal disorders
Alveolitis Allergic	1/108 (0.9%)
Chronic Obstructive Pulmonary Disease	1/108 (0.9%)
Lung Infiltration	1/108 (0.9%)
Pulmonary Embolism	3/108 (2.8%)
Skin and subcutaneous tissue disorders
Swelling Face	1/108 (0.9%)
Vascular disorders
Deep Vein Thrombosis	2/108 (1.9%)
Hypertension	1/108 (0.9%)
Peripheral Ischemia	1/108 (0.9%)
Thrombosis	1/108 (0.9%)
Other (Not Including Serious) Adverse Events
	E7389 Intravenous 1.4 mg/m2
	Affected / at Risk (%)	# Events
Total	107/108 (99.1%)
Blood and lymphatic system disorders
Anemia	38/108 (35.2%)
Leukopenia	30/108 (27.8%)
Neutropenia	46/108 (42.6%)
Thrombocytopenia	8/108 (7.4%)
Gastrointestinal disorders
Constipation	25/108 (23.1%)
Diarrhea	28/108 (25.9%)
Dry Mouth	6/108 (5.6%)
Dyspepsia	6/108 (5.6%)
Nausea	26/108 (24.1%)
Vomiting	11/108 (10.2%)
General disorders
Asthenia	31/108 (28.7%)
Fatigue	47/108 (43.5%)
Mucosal Inflammation	6/108 (5.6%)
Edema Peripheral	19/108 (17.6%)
Pain	11/108 (10.2%)
Pyrexia	18/108 (16.7%)
Infections and infestations
Urinary Tract Infection	10/108 (9.3%)
Investigations
Alanine Aminotransferase Increased	7/108 (6.5%)
Aspartate Aminotransferase Increased	8/108 (7.4%)
Metabolism and nutrition disorders
Anorexia	22/108 (20.4%)
Dehydration	6/108 (5.6%)
Hypokalemia	6/108 (5.6%)
Underweight	9/108 (8.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/108 (8.3%)
Back Pain	11/108 (10.2%)
Bone Pain	9/108 (8.3%)
Muscular Weakness	10/108 (9.3%)
Musculoskeletal Chest Pain	6/108 (5.6%)
Musculoskeletal Pain	7/108 (6.5%)
Myalgia	10/108 (9.3%)
Nervous system disorders
Dizziness	8/108 (7.4%)
Dysgeusia	5/108 (4.6%)
Headache	8/108 (7.4%)
Neuropathy	8/108 (7.4%)
Neuropathy Peripheral	15/108 (13.9%)
Paraesthesia	13/108 (12%)
Psychiatric disorders
Insomnia	7/108 (6.5%)
Respiratory, thoracic and mediastinal disorders
Cough	8/108 (7.4%)
Dyspnea	9/108 (8.3%)
Skin and subcutaneous tissue disorders
Alopecia	20/108 (18.5%)
Rash	7/108 (6.5%)
Vascular disorders
Hot Flush	6/108 (5.6%)

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.