Adenocarcinoma of the Pancreas, Pancreatic Cancer, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage II Pancreatic Cancer, Stage IV Pancreatic Cancer
Conditions
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.
Interventions
DRUGeribulin mesylate
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Median Survival Time | Up to 3 years | Estimated using the Kaplan-Meier method. |
| Overall Survival | At 6 months | 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. |
| 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. |
| 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 | — |
| 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 |
| Objective Stable Disease Rate | Upto 3 years | Objective stable disease rate Using RECIST |
| Time to Progression | At 6 months | Estimated using the Kaplan-Meier method. Median time to progression |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Eribulin Mesylate) 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). | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Treatment (Eribulin Mesylate) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 62 years |
| Region of Enrollment Canada | 15 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
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.
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Objective Response (Complete and Partial) Evaluated Using RECIST Criteria | 0 participants |
Secondary
Median Survival Time
Estimated using the Kaplan-Meier method.
Time frame: Up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Median Survival Time | 6 months |
Secondary
Median Time to Disease Progression
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Median Time to Disease Progression | 1.5 months |
Secondary
Objective Stable Disease Rate
Objective stable disease rate Using RECIST
Time frame: Upto 3 years
Population: Data was not collected
Secondary
Overall Survival
Estimated using the Kaplan-Meier method.
Time frame: At 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Overall Survival | 0 participants |
Secondary
Overall Survival
Estimated using the Kaplan-Meier method.
Time frame: At 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Overall Survival | 58 percentage of participants |
Secondary
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
Population: Data were not collected
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.
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Stable Disease Rate, Evaluated Using RECIST Criteria | 33 percentage of participants |
Secondary
Time to Progression
Estimated using the Kaplan-Meier method. Median time to progression
Time frame: At 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Time to Progression | 1.4 months |
Secondary
Time to Progression
Estimated using the Kaplan-Meier method.
Time frame: At 1 year
Population: Time to progression at 1 year not analyzed
Secondary
Toxicity
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Eribulin Mesylate) | Toxicity | 8 Types of adverse event |