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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00383760
• Other study ID #: NCI-2009-00173
• Secondary ID: PHL-049CDR000050
• Status: Completed
• Phase: Phase 2
• First received: September 29, 2006
• Last updated: September 19, 2017
• Start date: August 2006
• Est. completion date: July 2011

Study information

• Verified date: September 2017
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Pancreas
• Pancreatic Cancer
• Pancreatic Neoplasms
• Recurrent Pancreatic Cancer
• Stage II Pancreatic Cancer
• Stage III Pancreatic Cancer
• Stage IV Pancreatic Cancer

Intervention

Drug:
• eribulin mesylate
Given IV

Locations

Country	Name	City	State
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 3 years
Secondary	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.	Up to 3 years
Secondary	Median Survival Time	Estimated using the Kaplan-Meier method.	Up to 3 years
Secondary	Overall Survival	Estimated using the Kaplan-Meier method.	At 6 months
Secondary	Overall Survival	Estimated using the Kaplan-Meier method.	At 1 year
Secondary	Median Time to Disease Progression	Estimated using the Kaplan-Meier method.	Duration of time from start of treatment until the criteria for progression are met, assessed up to 3 years
Secondary	Time to Progression	Estimated using the Kaplan-Meier method.; Median time to progression	At 6 months
Secondary	Time to Progression	Estimated using the Kaplan-Meier method.	At 1 year
Secondary	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
Secondary	Toxicity	Types of Gr 3 or greater adverse events that are atleast possibly related to study drug	All patients will be evaluable for toxicity from the time of their first treatment with E7389.
Secondary	Objective Stable Disease Rate	Objective stable disease rate Using RECIST	Upto 3 years