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

Phase 2

Completed

Conditions: Pancreatic Cancer
Adenocarcinoma of the Pancreas
Stage IV Pancreatic Cancer
Stage II Pancreatic Cancer
Recurrent Pancreatic Cancer
Stage III Pancreatic Cancer

Interventions: Drug: eribulin mesylate

Registration Number: NCT00383760

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (eribulin mesylate)	eribulin mesylate	Patients receive E7389 IV on days 1 and 8.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Overall Survival	At 1 year	Estimated using the Kaplan-Meier method.
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
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
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.
Median Survival Time	Up to 3 years	Estimated using the Kaplan-Meier method.
Time to Progression	At 1 year	Estimated using the Kaplan-Meier method.
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.
Objective Stable Disease Rate	Upto 3 years	Objective stable disease rate Using RECIST