Eribulin Plus Gemcitabine (EG) vs Paclitaxel Plus Gemcitabine (PG) in HER2-Negative Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

— EG_PG  

Official title:

A Phase II, Multicenter, Randomized Trial of Eribulin Plus Gemcitabine (EG) vs.Paclitaxel Plus Gemcitabine (PG) in Patients With HER2-Negative Metastatic Breast Cancer as First -Line Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02263495
• Other study ID #: 2014-0857
• Status: Completed
• Phase: Phase 2
• Start date: December 19, 2014
• Est. completion date: June 17, 2019

Study information

• Verified date: July 2020
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Metastatic breast cancer (MBC) is an incurable disease and is needed to improve effective chemotherapy. Paclitaxel plus Gemcitabine (PG) combination chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC, and was found to be proper as a maintenance chemotherapy regimen with survival benefit and feasible toxicity profile as shown in a large phase III KCSG (Korean Cancer Study Group) study (Park Y et al. J Clin Oncol 31(14):1732, 2013).

Eribulin mesylate is a microtubule-targeting agent that showed improved overall survival benefit as monotherapy for MBC patients as a new chemotherapeutic agent after failure of anthracycline and taxane in EMBRACE study (Cortes J et. al. Lancet 377:914-923, 2011). Eribulin was also reported its promising efficacy in another randomized phase III study that demonstrated eribulin as efficacious as capecitabine (Kaufman P et. al. Abstr# S6-6, SABCS 2012). Both study results showed potential clinical benefit in patients with triple negative MBC (TNBC). Thus, eribulin combined with gemcitabine may be a new potential regimen for early line therapy in patients with metastatic breast cancer.

Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Although there is no direct evidence that eribulin has better neurotoxicity profile than taxane, eribulin tended to show less neurotoxicity compared with ixabepilone in a phase II trial (Vahdat, L et al. 2011 SABCS). Eribulin has no worsen toxicity as compared to paclitaxel. Therefore, EG may have less neurotoxicity comparing to PG.

In phase I trial, eribulin in combination with gemcitabine was feasible in patients with advanced solid tumor treated with chemotherapy (< 3 lines) (Goel R, et al, 2009 ASCO).

Based on this rationale, the investigators are to conduct randomized phase II study comparing EG chemotherapy with PG chemotherapy for patients with HER-2 negative MBC as first-line chemotherapy.

A total of 118 patients will be recruited. Patients will be randomized to a treatment arm by permutated method. The randomization ratio is 1:1. This study is multi-center, randomized, open label study.

Description:

A total of enrolled 118 patients in EG and PG groups, will be provided chemotherapy regimen:

Paclitaxel/Gemcitabine (PG) : every 3 weeks D1 Paclitaxel 175mg/m2 + D5W 500mL MIV over 3hrs before gemcitabine administration D1, D8 Gemcitabine 1,250 mg/m2 + NormalSaline 100ml MIV over 30mins

• Pre & Post medication (which can be changed according to institutions' policy) D1 Corticosteroid 100 mg i.v. 30 min. before Paclitaxel Pheniramine 1A + D5W 50mL MIV 30mins before Paclitaxel Ranitidine 50mg IV + D5W 50mL MIV 30mins before Paclitaxel HT3 antagonist 1A + D5W 50 mL MIV 30mins before Paclitaxel

Eribulin/Gemcitabine (EG): every 3weeks D1, D8 Eribulin 1.0 mg/m2, 2-5min iv before gemcitabine (or miv with NormalSaline 100ml in max.) D1, D8 Gemcitabine 1000 mg/m2 + NormalSaline100ml MIV over 30mins

1. screening /baseline

• obtaining Informed consent form

• collecting information

• demographic data

• breast cancer treatment history/ medical history

• general physical examination/ vital sign & Performance status

• Test: CBC/blood chemistry/ Tumor response(CT or MRI)/

• collecting QOL questionnaire using FACT-Taxane

2. cycle 1 ~ prior to EOT

• general physical examination/ vital sign & Performance status

• Test: CBC/blood chemistry/ Tumor response(CT or MRI)

• collecting QOL questionnaire using FACT-Taxane

• administration PG or EG

3. EOT(end of treatment)

• general physical examination/ vital sign & Performance status

• Test: CBC/blood chemistry/ Tumor response(CT or MRI)

• collecting QOL questionnaire using FACT-Taxane

4. survival follow up(every 12weeks)

• survival

• anti neoplastic therapy after end of treatment

• The tumor response will be performed every 12 (±2) weeks until disease progression

Subjects may be withdrawn from the study (i.e. from any further study medication or study procedure) for the following reasons:

• At their own request

• If, in the investigator's opinion, continuation in the study would be detrimental to the subject's well-being

• In case of disease progression

• In case of unacceptable toxicity

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: June 17, 2019
• Est. primary completion date: May 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed metastatic, or recurrent breast cancer

2. HER2-negative breast cancer

3. age > 18 years

4. ECOG performance status 0 - 2

5. Pre- or postmenopausal breast cancer patients with measurable or non-measurable lesions, who are candidates for chemotherapy

6. Life expectancy = 3 months

7. No prior history of chemotherapy for metastatic, recurrent breast cancer

8. Patients may have received prior neoadjuvant or adjuvant taxane regimen as long as it has been 12 months since completion of regimen.

9. Patients either may or may not have a prior anthracycline containing regimen.

10. Prior hormonal therapy as a treatment of metastatic disease is allowed. But antitumoral hormonal therapy must be terminated prior to enrollment(up to the date of randomization)

11. Prior radiation therapy allowed as long as < 25% of the bone marrow has been treated, and the patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed 2 weeks before study entry.

12. Bisphosphonates for the treatment of bone metastases should not be initiated following the first dose of randomized therapy. It must be initiated prior to day of treatment (cycle 1, day 1). Patients may continue on bisphosphonates who already established on bisphosphonate therapy for bone metastases

13. Adequate bone marrow function (= ANC 1,500/ul, = platelet 100,000/ul, = Hemoglobin 9.0 g/dl)

14. Adequate renal function (= serum creatinine 1.5 mg/dl or CCr = 50 ml/min)

15. Adequate liver function (= serum bilirubin 1.5 mg/dl, = AST & ALTX3 upper normal limit or AST and ALT = 5.0XULN if judged by the investigator to be related to liver metastases)

16. Written informed consent

Exclusion Criteria:

1. Serious uncontrolled intercurrent infections

2. Serious intercurrent medical or psychiatric illness, including active cardiac disease

3. Pregnancy or breast feeding

4. Second primary malignancy(except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence)

5. Documented parenchymal or leptomeningeal brain metastasis

6. Peripheral neuropathy = grade 2

7. Prior treatment with gemcitabine will not be allowed.

8. HER-2 overexpressing breast cancer and concomitant trastuzumab treatment is not allowed

9. Women of childbearing potential, unwilling to use a medically acceptable method of contraception during the trial

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Paclitaxel
175mg/m2 + D5W 500mL MIV over 3hrs before gemcitabine administration
• Eribulin
1.0 mg/m2, 2-5min iv before gemcitabine (or miv with NS 100ml in max.)
• Gemcitabine
PG:1250mg/m2 + NS 100ml MIV over 30mins EG:1000mg/m2 + NS 100ml MIV over 30mins

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (4)

Lead Sponsor	Collaborator
Asan Medical Center	Dong-A ST Co., Ltd., Eisai Inc., Samyang Biopharmaceuticals Corporation

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	To demonstrate that EG is not inferior to PG group in terms of PFS in patients with metastatic or recurrent breast cancer as first-line treatment.	48months
Secondary	overall survival	Survival will be measured as the time from randomization to the date of death.	48months
Secondary	neuropathic scale	FACT for Taxane QOL assessment	expected at 9week , expected at 24week
Secondary	toxicity of study drugs	Using CTCAE Version 4.0	from first administration until 28 days after the last dose administration
Secondary	duration of response	using RECIEST version 1.1	48months
Secondary	objective response rate	using RECIEST version 1.1	48months
Secondary	clinical benefit rate	using RECIEST version 1.1	48months