- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00410553
Eribulin Mesylate and Gemcitabine Hydrochloride in Treating Patients With Metastatic Solid Tumors or Solid Tumors That Cannot be Removed by Surgery
A Phase I Study of Halichondrin B Analog E7389 in Combination With Gemcitabine in Patients With Refractory or Advanced Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
I. Determine the recommended phase II dose (RPTD) of E7389 (eribulin mesylate) when given in combination with gemcitabine (gemcitabine hydrochloride) in patients with advanced cancer.
II. Determine the safety, tolerability, and toxicity profile of E7389 and gemcitabine given in combination.
III. Assess the antitumor activity of E7389 in combination with gemcitabine in patients with measurable disease.
IV. Determine the pharmacokinetic profile of E7389 and gemcitabine to assess for any possible interactions between the two agents.
OUTLINE: This is a multicenter, dose-escalation study. Patients receive eribulin mesylate intravenously (IV) and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 OR on days 1 and 8.
Courses repeat every 28 or 21 days* in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of eribulin mesylate and gemcitabine hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). NOTE: *If DLT is observed at the first dose level of the 28-day schedule, subsequent patients are treated on days 1 and 8 of the 21-day schedule; patients enrolled in the expansion cohort (patients with ovarian or endometrial cancer or chemotherapy-naive or minimally pre-treated cancer) receive treatment according to the 21-day schedule.
After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ontario
-
Ottawa, Ontario, Canada, K1Y 4E9
- Ottawa Hospital-Civic Campus
-
Toronto, Ontario, Canada, M5G 2M9
- University Health Network-Princess Margaret Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative antineoplastic drug treatments do not exist or are no longer effective:
- Ovarian/Endometrial Expansion Cohort: Patients must have histologically or cytologically confirmed ovarian or endometrial malignancy that is metastatic or unresectable and for which standard curative antineoplastic drug treatments do not exist or are no longer effective
CHEMOTHERAPY: Patients may have had up to two prior chemotherapy regimens for advanced or metastatic incurable solid tumors; prior (neo) adjuvant chemotherapy is allowed and not considered among the maximum of two prior regimens; patients must have completed any prior chemotherapy at least 4 weeks prior to registration; prior treatment with gemcitabine is not allowed
- Chemo Naïve/Minimally Pre-Treated Cohort: Patients may not have received any prior chemotherapy for metastatic disease; prior adjuvant chemotherapy is allowed; patients must have completed any prior chemotherapy at least 4 weeks prior to registration; prior treatment with gemcitabine is not allowed
- RADIATION: patients may have received prior radiation, however this must have been completed at least 4 weeks prior to registration; patients must not have had more than 40% of their bone marrow irradiated and must have either measurable disease outside the field or progression post radiation therapy
- SURGERY: patients may have had prior surgery; patients must be at least 4 weeks from any major surgery prior to registration on the study
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 (Karnofsky >= 60%)
- Life expectancy > 3 months
- Leukocytes >= 3 x 10^9/L
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Since cytochrome P450 (CYP)3A4 appears to be the major enzyme responsible for the human hepatic metabolism of E7389 in vitro, the concurrent use of inhibitors and inducers of CYP3A4 are prohibited during the study treatment period; concurrent use of CYP3A4 substrates are allowed, however, use caution and monitor the patient for potential drug interactions
- The effects of E7389 on the developing human fetus are unknown; for this reason and because antitubulin agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing 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; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who have had chemotherapy, biologic therapy, hormonal therapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered to < Common Terminology Criteria for Adverse Events (CTCAE) grade 2 from adverse events due to agents administered more than 4 weeks earlier are not eligible to participate in this study; grade 1 persisting toxicities or those deemed irreversible will not be exclusionary; patients who have received prior gemcitabine are also excluded
- Patients may not be receiving any other investigational agents concurrently; patients should not be receiving any other anticancer therapy while on study, such as hormonal, biologic, or targeted therapies
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to E7389 or gemcitabine used in study
- 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 requirements
- Pregnant women are excluded from this study because E7389 is an antitubulin agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7389, breastfeeding should be discontinued if the mother is treated with E7389; these potential risks may also apply to other agents used in this study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with E7389; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (combination chemotherapy)
Patients receive eribulin mesylate IV and gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 OR on days 1 and 8. Courses repeat every 28 or 21 days* in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose of eribulin mesylate administered with gemcitabine hydrochloride in advanced/metastatic solid tumors
Time Frame: Course 1
|
The Common Terminology Criteria for Adverse Events (CTCAE version 3 will be used to grade toxicity.
|
Course 1
|
Recommended phase II dose of eribulin mesylate in combination with gemcitabine hydrochloride
Time Frame: Course 1
|
Defined as one dose level below the dose at which 2 or more patients experience a DLT.
If =< 1 DLT is observed at dose level 5, then this will be the RPTD.
|
Course 1
|
Safety, tolerability, toxicity profile, and dose-limiting toxicity of eribulin mesylate
Time Frame: From the time of their first treatment with eribulin mesylate
|
Graded using the CTCAE version 3.
|
From the time of their first treatment with eribulin mesylate
|
Pharmacokinetic profiles of eribulin mesylate and gemcitabine hydrochloride
Time Frame: Days 1, 2, 3, 5, and 8 of course 1
|
Plasma samples for the determination of eribulin mesylate plasma concentration will be analyzed in conjunction with Eisai Pharmaceuticals.
Plasma samples for the determination of gemcitabine plasma concentration will be analyzed through methods developed at the Princess Margaret Hospital.
|
Days 1, 2, 3, 5, and 8 of course 1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Preliminary clinical antitumor activity of eribulin mesylate
Time Frame: Baseline, every 2 courses, and 4 weeks post-treatment
|
Assessed using radiologic images (CT scans).
Measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
|
Baseline, every 2 courses, and 4 weeks post-treatment
|
Objective response rate in patients with measurable disease
Time Frame: Baseline, every 2 courses, and 4 weeks post-treatment
|
Measured by RECIST criteria.
All tests will be two-sided and a p-value of 0.05 or less will be considered statistically significant.
Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest.
95% confidence intervals will be provided for estimates of interest where possible.
|
Baseline, every 2 courses, and 4 weeks post-treatment
|
Duration of response in patients with measurable disease
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
|
Estimated using the Kaplan-Meier method.
|
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
|
Time to disease progression in patients with measurable disease
Time Frame: From start of treatment until the criteria for progression are met
|
Estimated using the Kaplan-Meier method.
|
From start of treatment until the criteria for progression are met
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rakesh Goel, University Health Network-Princess Margaret Hospital
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Disease Attributes
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Carcinoma
- Recurrence
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Gemcitabine
- Halichondrin B
Other Study ID Numbers
- NCI-2009-00172 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- N01CM17107 (U.S. NIH Grant/Contract)
- N01CM00032 (U.S. NIH Grant/Contract)
- CDR0000520315
- PMH-PHL-048
- PHL-048 (Other Identifier: University Health Network-Princess Margaret Hospital)
- 7444 (Other Identifier: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Ovarian Carcinoma
-
National Cancer Institute (NCI)NRG OncologyActive, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Seromucinous Carcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Primary Peritoneal High Grade Serous Adenocarcinoma | Ovarian High Grade Serous Adenocarcinoma | Fallopian... and other conditionsUnited States, Puerto Rico
-
National Cancer Institute (NCI)NRG OncologyActive, not recruitingOvarian Seromucinous Carcinoma | Recurrent Ovarian High Grade Serous Adenocarcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Fallopian Tube Mucinous Adenocarcinoma | Recurrent Fallopian Tube Clear Cell Adenocarcinoma | Recurrent Fallopian Tube Endometrioid Adenocarcinoma | Recurrent... and other conditionsUnited States, Puerto Rico
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Merck Sharp & Dohme LLC; Celldex TherapeuticsRecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Endometrial Serous Adenocarcinoma | Ovarian Clear Cell Adenocarcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Platinum-Sensitive Ovarian Carcinoma | Recurrent Fallopian... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...National Institutes of Health (NIH)TerminatedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Malignant Ovarian Endometrioid Tumor | Malignant Ovarian Serous TumorUnited States
-
Radboud University Medical CenterDutch Cancer SocietyRecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal CarcinomaNetherlands
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Recurrent Ovarian Germ Cell Tumor | Undifferentiated Ovarian Carcinoma | Ovarian Serous...United States
-
Northwestern UniversityNational Cancer Institute (NCI); Ipsen BiopharmaceuticalsCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Refractory Ovarian Carcinoma | Refractory Fallopian Tube... and other conditionsUnited States
-
University of MiamiWithdrawnOvarian Cancer | Recurrent Ovarian Carcinoma | Ovarian Carcinoma | Recurrent Ovarian Cancer
-
Roswell Park Cancer InstituteCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Tumor | Fallopian Tube Endometrioid Tumor | Ovarian Endometrioid Tumor | Fallopian Tube Mucinous Neoplasm | Fallopian Tube Serous Neoplasm | Ovarian Serous Tumor | Ovarian Mucinous...United States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Ovarian Undifferentiated CarcinomaUnited States
Clinical Trials on Gemcitabine Hydrochloride
-
Mayo ClinicNational Cancer Institute (NCI)TerminatedStage III Renal Pelvis Cancer AJCC v8 | Stage III Ureter Cancer AJCC v8 | Stage IV Renal Pelvis Cancer AJCC v8 | Stage IV Ureter Cancer AJCC v8 | Stage III Renal Pelvis and Ureter Cancer AJCC v8 | Stage IV Renal Pelvis and Ureter Cancer AJCC v8 | Stage 0a Renal Pelvis and Ureter Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Beth ChristianCompletedRecurrent Adult Hodgkin Lymphoma | Adult Lymphocyte Depletion Hodgkin Lymphoma | Adult Lymphocyte Predominant Hodgkin Lymphoma | Adult Mixed Cellularity Hodgkin Lymphoma | Adult Nodular Sclerosis Hodgkin Lymphoma | Adult Nodular Lymphocyte Predominant Hodgkin LymphomaUnited States
-
National Cancer Institute (NCI)CompletedStage IV Ovarian Epithelial Cancer | Primary Peritoneal Cavity Cancer | Recurrent Ovarian Epithelial Cancer | Stage III Ovarian Epithelial CancerUnited States
-
NCIC Clinical Trials GroupCompleted
-
OSI PharmaceuticalsNational Cancer Institute (NCI)CompletedPancreatic Cancer | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Adult Burkitt Lymphoma | Recurrent Adult Diffuse Large Cell Lymphoma | Recurrent Adult Diffuse Mixed Cell Lymphoma | Recurrent Adult Diffuse Small Cleaved Cell Lymphoma and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedAdenocarcinoma of the Pancreas | Recurrent Pancreatic Cancer | Stage III Pancreatic Cancer | Stage II Pancreatic CancerUnited States
-
NCIC Clinical Trials GroupCompleted
-
Institute of Liver and Biliary Sciences, IndiaRecruiting