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

Primary Purpose

Adenocarcinoma of the Pancreas, Pancreatic Cancer, Recurrent Pancreatic Cancer

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
eribulin mesylate
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Pancreas

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (eribulin mesylate)

Arm Description

Patients receive E7389 IV on days 1 and 8.

Outcomes

Primary Outcome Measures

Objective Response (Complete and Partial) Evaluated Using RECIST Criteria
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

Stable Disease Rate, Evaluated Using RECIST Criteria
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.
Median Survival Time
Estimated using the Kaplan-Meier method.
Overall Survival
Estimated using the Kaplan-Meier method.
Overall Survival
Estimated using the Kaplan-Meier method.
Median Time to Disease Progression
Estimated using the Kaplan-Meier method.
Time to Progression
Estimated using the Kaplan-Meier method. Median time to progression
Time to Progression
Estimated using the Kaplan-Meier method.
Response Duration
Toxicity
Types of Gr 3 or greater adverse events that are atleast possibly related to study drug
Objective Stable Disease Rate
Objective stable disease rate Using RECIST

Full Information

First Posted
September 29, 2006
Last Updated
September 19, 2017
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00383760
Brief Title
Eribulin Mesylate as Second-Line Therapy for Locally Advanced, Unresectable, or Metastatic Pancreatic Cancer Patients
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 Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
Detailed Description
PRIMARY OBJECTIVE: I. 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: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Pancreas, Pancreatic Cancer, Recurrent Pancreatic Cancer, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (eribulin mesylate)
Arm Type
Experimental
Arm Description
Patients receive E7389 IV on days 1 and 8.
Intervention Type
Drug
Intervention Name(s)
eribulin mesylate
Other Intervention Name(s)
B1939, E7389, ER-086526, halichrondrin B analog
Intervention Description
Given IV
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
Title
Median Survival Time
Description
Estimated using the Kaplan-Meier method.
Time Frame
Up to 3 years
Title
Overall Survival
Description
Estimated using the Kaplan-Meier method.
Time Frame
At 6 months
Title
Overall Survival
Description
Estimated using the Kaplan-Meier method.
Time Frame
At 1 year
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
Title
Time to Progression
Description
Estimated using the Kaplan-Meier method. Median time to progression
Time Frame
At 6 months
Title
Time to Progression
Description
Estimated using the Kaplan-Meier method.
Time Frame
At 1 year
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
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.
Title
Objective Stable Disease Rate
Description
Objective stable disease rate Using RECIST
Time Frame
Upto 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Malcolm Moore
Organizational Affiliation
University Health Network-Princess Margaret Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

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

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