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

• ClinicalTrials.gov Identifier: NCT00383760
• Recruitment Status: Completed
• First Posted: October 3, 2006
• Results First Posted: December 9, 2016
• Last Update Posted: October 20, 2017
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

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:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• 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: August 2006
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: July 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 3 years ]
   Estimated using the Kaplan-Meier method.
3. Overall Survival [ Time Frame: At 6 months ]
   Estimated using the Kaplan-Meier method.
4. Overall Survival [ Time Frame: At 1 year ]
   Estimated using the Kaplan-Meier method.
5. Median Time to Disease Progression [ Time Frame: 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 [ Time Frame: At 6 months ]

   Estimated using the Kaplan-Meier method.

   Median time to progression

7. Time to Progression [ Time Frame: At 1 year ]
   Estimated using the Kaplan-Meier method.
8. 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 ]
9. Toxicity [ Time Frame: 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 [ Time Frame: Upto 3 years ]
    Objective stable disease rate Using RECIST

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Canada, Ontario

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

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00383760
• Other Study ID Numbers: NCI-2009-00173; PHL-049 ( Other Grant/Funding Number: N01CM17107 ); CDR0000502291 ( Other Grant/Funding Number: N01CM17107 ); N01CM62203 ( U.S. NIH Grant/Contract )
• First Posted: October 3, 2006
• Results First Posted: December 9, 2016
• Last Update Posted: October 20, 2017
• Last Verified: September 2017

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases