Eribulin Mesylate as Second-Line Therapy for Locally Advanced, Unresectable, or Metastatic Pancreatic Cancer Patients

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00383760
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 59
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II trial is studying how well E7389 works as second-line therapy in treating patients with locally advanced, unresectable, or metastatic pancreatic cancer. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Pancreas; Pancreatic Cancer; Recurrent Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer	Drug: eribulin mesylate	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. To determine the objective response (complete and partial) to E7389 in patients with locally advanced, unresectable, or metastatic pancreatic adenocarcinoma that progressed after prior gemcitabine hydrochloride-based therapy.

SECONDARY OBJECTIVE:

1. To determine the antitumor activity of E7389, in terms of median survival, 1-year survival rate, response or stable disease duration, toxicity, and time to disease progression, in these patients.

OUTLINE: This is an open-label, multicenter study. Patients receive eribulin mesylate IV on days 1 and 8. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed at 4 weeks. Patients with complete response, partial response, or stable disease are followed every 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the Halichondrin B Analog E7389 as Second Line Therapy for Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (eribulin mesylate) Patients receive E7389 IV on days 1 and 8.	Drug: eribulin mesylate; Given IV; Other Names: B1939 E7389 ER-086526 halichrondrin B analog

Outcome Measures

Primary Outcome Measures

1. Objective Response (Complete and Partial) Evaluated Using RECIST Criteria [Up to 3 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

Secondary Outcome Measures

1. Stable Disease Rate, Evaluated Using RECIST Criteria [Up to 3 years]

   Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

2. Median Survival Time [Up to 3 years]

   Estimated using the Kaplan-Meier method.

3. Overall Survival [At 6 months]

   Estimated using the Kaplan-Meier method.

4. Overall Survival [At 1 year]

   Estimated using the Kaplan-Meier method.

5. Median Time to Disease Progression [Duration of time from start of treatment until the criteria for progression are met, assessed up to 3 years]

   Estimated using the Kaplan-Meier method.

6. Time to Progression [At 6 months]

   Estimated using the Kaplan-Meier method. Median time to progression

7. Time to Progression [At 1 year]

   Estimated using the Kaplan-Meier method.

8. Response Duration [From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years]

9. Toxicity [All patients will be evaluable for toxicity from the time of their first treatment with E7389.]

   Types of Gr 3 or greater adverse events that are atleast possibly related to study drug

10. Objective Stable Disease Rate [Upto 3 years]

    Objective stable disease rate Using RECIST

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically/cytologically confirmed pancreatic carcinoma (locally advanced, unresectable or metastatic)

• measurable disease (at least 1 lesion accurately measured in at least 1 dimension (longest diameter as >20mm with conventional techniques or >10mm with spiral CT scan)

• =4 weeks from any major surgery

• Up to 1 prior line of gemcitabine based systemic therapy (single agent/combination therapy) for locally advanced/metastatic disease with evidence of disease progression. Prior therapy with inhibitors of angiogenesis and/or the epidermal growth factor receptor permitted. Last chemotherapy dose >=4 weeks prior to randomization.

• May have received prior 5FU (+/- folinic acid)/gemcitabine given concurrently with radiation as a "radiation sensitizer". Last chemotherapy dose >=4 weeks prior to randomization.

• Prior radiation treatment >=4 weeks prior to randomization

• Age >18 years.

• Life expectancy >=3 months

• ECOG< 2(Karnofsky-60%)

• leukocytes>3,000/mcL

• absolute neutrophil count>1,500/mcL

• platelets>100,000/mcL

• total bilirubin < 1.5 UNL

• AST/ALT≤2.5x institutional ULN

• creatinine within institution limits OR creatinine clearance>60mL/min/1.73m2 for patients with creatinine levels above institution limits

• concurrent use of inhibitors/inducers of CYP3A4 are prohibited during the study treatment period

• effects of E7389 on developing human fetus are unknown. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

• Ability to understand/willingness to sign written informed consent

Exclusion Criteria:

• chemotherapy/radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• May not be receiving other investigational agents

• Known brain metastases

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to E7389

• Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study

• Pregnant women excluded because E7389 is an antitubulin agent with the potential for teratogenic/abortifacient effects

• HIV-positive patients on combination antiretroviral therapy are ineligible because of potential for p PK interactions with E7389

• Other active malignancies in past 5 years except for cervical carcinoma in situ and non-melanomatous skin cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Malcolm Moore, University Health Network-Princess Margaret Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00383760
• Other Study ID Numbers: NCI-2009-00173; PHL-049; CDR0000502291; N01CM62203
• First Posted: Oct 3, 2006
• Last Update Posted: Oct 20, 2017
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Pancreatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	E7389
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: 1.4mg/m2 given IV weekly day 1,8 every 21 days (1 cycle).
Overall Participants	15
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 66.7%
>=65 years	5 33.3%
Sex: Female, Male (Count of Participants)
Female	8 53.3%
Male	7 46.7%
Region of Enrollment (participants) [Number]
Canada	15 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response (Complete and Partial) Evaluated Using RECIST Criteria
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Number [participants]	0 0%

2. Secondary Outcome

Title	Stable Disease Rate, Evaluated Using RECIST Criteria
Description	Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Number (95% Confidence Interval) [percentage of participants]	33 220%

3. Secondary Outcome

Title	Median Survival Time
Description	Estimated using the Kaplan-Meier method.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Median (95% Confidence Interval) [months]	6

4. Secondary Outcome

Title	Overall Survival
Description	Estimated using the Kaplan-Meier method.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Number (95% Confidence Interval) [percentage of participants]	58 386.7%

5. Secondary Outcome

Title	Overall Survival
Description	Estimated using the Kaplan-Meier method.
Time Frame	At 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Number [participants]	0 0%

6. Secondary Outcome

Title	Median Time to Disease Progression
Description	Estimated using the Kaplan-Meier method.
Time Frame	Duration of time from start of treatment until the criteria for progression are met, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Median (95% Confidence Interval) [months]	1.5

7. Secondary Outcome

Title	Time to Progression
Description	Estimated using the Kaplan-Meier method. Median time to progression
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Median (95% Confidence Interval) [months]	1.4

8. Secondary Outcome

Title	Time to Progression
Description	Estimated using the Kaplan-Meier method.
Time Frame	At 1 year

Outcome Measure Data

Analysis Population Description

Time to progression at 1 year not analyzed

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	0

9. Secondary Outcome

Title	Response Duration
Time Frame	From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	E7389
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	0

10. Secondary Outcome

Title	Toxicity
Description	Types of Gr 3 or greater adverse events that are atleast possibly related to study drug
Time Frame	All patients will be evaluable for toxicity from the time of their first treatment with E7389.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	E7389
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	15
Number [Types of adverse event]	8

11. Secondary Outcome

Title	Objective Stable Disease Rate
Description	Objective stable disease rate Using RECIST
Time Frame	Upto 3 years

Outcome Measure Data

Analysis Population Description

Data was not collected

Arm/Group Title	E7389
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
Measure Participants	0

Adverse Events

Arm/Group Title	Treatment (Eribulin Mesylate)
Arm/Group Description	Patients receive E7389 IV on days 1 and 8. eribulin mesylate: Given IV
All Cause Mortality
	Treatment (Eribulin Mesylate)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Eribulin Mesylate)
	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)
Gastrointestinal disorders
Constipation	1/15 (6.7%)
General disorders
Death NOS	2/15 (13.3%)
Investigations
Creatinine increased	1/15 (6.7%)
Renal and urinary disorders
Urinary tract obstruction	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Dry skin	1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	Treatment (Eribulin Mesylate)
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Anemia	13/15 (86.7%)
Gastrointestinal disorders
Abdominal pain	13/15 (86.7%)
Nausea	12/15 (80%)
Constipation	10/15 (66.7%)
General disorders
Fatigue	12/15 (80%)
Investigations
Lymphocyte count decreased	14/15 (93.3%)
Alkaline phosphatase increased	12/15 (80%)
White blood cell decreased	10/15 (66.7%)
Alanine aminotransferase increased	9/15 (60%)
Neutrophil count decreased	9/15 (60%)
Metabolism and nutrition disorders
Hypoalbuminemia	11/15 (73.3%)
Hyperglycemia	10/15 (66.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.