Eribulin Mesylate and Gemcitabine Hydrochloride in Treating Patients With Metastatic Solid Tumors or Solid Tumors That Cannot be Removed by Surgery

NCT00410553 | Completed Phase 1

• 7 other identifiers: NCI-2009-00172CDR0000520315PMH-PHL-048PHL-0487444N01CM00032N01CM17107
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial is studying the side effects and best dose of eribulin mesylate and gemcitabine hydrochloride in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as eribulin mesylate and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Conditions

Adult Solid Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Uterine Corpus Cancer AJCC v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Uterine Corpus Cancer AJCC v7

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose of eribulin mesylate administered with gemcitabine hydrochloride in advanced/metastatic solid tumors

  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

  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

  Graded using the CTCAE version 3.

  From the time of their first treatment with eribulin mesylate

• Pharmacokinetic profiles of eribulin mesylate and gemcitabine hydrochloride

  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 Outcomes (4)

• Preliminary clinical antitumor activity of eribulin mesylate

  Baseline, every 2 courses, and 4 weeks post-treatment

• Objective response rate in patients with measurable disease

  Baseline, every 2 courses, and 4 weeks post-treatment

• Duration of response in patients with measurable disease

  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

  From start of treatment until the criteria for progression are met

Study Arms (1)

Treatment (combination chemotherapy)

EXPERIMENTAL

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.

Drug: Eribulin Mesylate; Drug: Gemcitabine Hydrochloride

Interventions

Eribulin Mesylate DRUG

Given IV

Also known as: B1939 Mesylate, E7389, ER-086526, Halaven, Halichondrin B Analog

Treatment (combination chemotherapy)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

Treatment (combination chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Ottawa Hospital-Civic Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• Lheureux S, Oza AM, Laurie SA, Halford R, Jonker D, Chen E, Keller D, Bourade V, Wang L, Doyle L, Siu LL, Goel R. A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium. Br J Cancer. 2015 Dec 1;113(11):1534-40. doi: 10.1038/bjc.2015.343. Epub 2015 Nov 10.

  PMID: 26554651 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

eribulin; Gemcitabine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Rakesh Goel

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 13, 2006
• Study Start: November 14, 2006
• Primary Completion: October 24, 2012
• Study Completion: October 24, 2012
• Last Updated: October 3, 2018

Record last verified: 2018-10

Locations

CA (2)