Lapatinib+Vinorelbine vs Vinorelbine HER2 Positive Metastatic Breast Cancer Progressed After Lapatinib/Trastuzumab

NCT01730677 | Unknown Phase 2

• 1 other identifier: NCCCTS-11-583
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators address the clinical efficacy of continuing lapatinib treatment combined with vinorelbine after the progression of both trastuzumab and lapatinib treatment compared with vinorelbine alone in HER2 positive metastatic breast cancer patients.

Conditions

Metastatic Breast Cancer

Keywords

Lapatinib; Vinorelbine

Outcome Measures

Primary Outcomes (1)

• Progression free survival rate at 18 weeks

  The PFS rate at 18 weeks will be calculated as the ratio of patients on the study to Intent to treat (ITT) population at the time point of 18 weeks from the initiation of study treatment. The ITT population will consist of all patients who are randomized.

  The time point of 18 weeks from the initiation of study treatment.

Secondary Outcomes (4)

• Progression free survival (PFS)

  From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months

• Overall survival (OS)

  From date of randomization until the date of death from any cause, assessed up to 36 months

• toxicity

  From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months

• response rate

  From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months

Study Arms (2)

Lapatinib+Vinorelbine

EXPERIMENTAL

lapatinib 1000mg, once daily vinorelbine 20mg/m2, D1 and D8, every 3 weeks

Drug: Lapatinib; Drug: Vinorelbine

Vinorelbine

NO INTERVENTION

vinorelbine 30mg/m2, D1 and D8, every 3 weeks

Interventions

Lapatinib DRUG

lapatinib 1000mg, once daily

Also known as: LV arm

Lapatinib+Vinorelbine

Vinorelbine DRUG

Vinorelbine 20mg/m2, D1 and D8, every 3 weeks

Also known as: LV arm

Lapatinib+Vinorelbine

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed stage IV or recurrent breast cancer
• Documented HER2 status and positive for HER2 in tumor cells by immunohistochemistry (3+) or FISH (The results of SISH or CISH are also allowed)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Age ≥ 20 years
• Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1
• Patients who were treated with anthracycline based regimens in the adjuvant/neoadjuvant or metastatic setting.
• Patients who experienced disease progression after the treatment with lapatinib containing regimens whose response were more than stable disease (including CR, PR, SD≥ 12 weeks) during treatment. There is no limitation on the time interval between the stop of lapatinib treatment and the study enrollment.
• Patients must have received 2 or 3 lines of prior anti-HER2 therapy in metastatic setting as follows regardless of the order
• In case with trastuzumab: monotherapy or combined with taxane or combined with AI
• In case with lapatinib: monotherapy or combined with capecitabine or combined with AI
• Patients who received T-DM1 or pertuzumab with trastuzumab previously are allowed in this study
• Patients who received neratinib, mTOR inhibitor, PI3K/AKT inhibitor, or BIBW2992 are not eligible
• Patients who experienced a disease recurrence during receiving adjuvant trastuzumab or within 6 months after the completion of adjuvant trastuzumab treatment are allowed even when patients did not receive trastuzumab in the metastatic setting.
• Patients who experienced a disease recurrence during receiving adjuvant lapatinib or within 6 months after the completion of adjuvant lapatinib treatment are allowed as long as they meet criteria of CR, PR or SD ≥ 12 weeks by lapatinib/capecitabine treatment for metastatic disease.
• Central nervous system metastasis is permitted if asymptomatic or controlled with minimal steroid requirement and is documented to be non-progressing at study entry.

You may not qualify if:

• Pregnant or lactating women or women of childbearing potential, including women whose last menstrual period was ,12 months ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during the study treatment period.
• Patients who received vinorelbine treatment in metastatic setting.
• Patients who received more than 3 lines of prior anti-HER2 therapy in metastatic setting
• Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer
• Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative colitis)
• current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Concurrent disease or serious medical disorder,
• Serious cardiac illness :
• History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF \<50%) High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrioventricular (AV)-block,supraventricular arrhythmias, prolonged corrected QT (QTc) which are not adequately rate-controlled) Angina pectoris requiring antianginal medication Clinically significant valvular heart disease Evidence of transmural infarction on ECG Poorly controlled hypertension (e.g. systolic \>180mm Hg or diastolic \>100mm Hg)
• \- known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients.

Sponsors & Collaborators

• National Cancer Center, Korea: lead
• Asan Medical Center: collaborator
• Chung-Ang University: collaborator
• Korea University Anam Hospital: collaborator
• Samsung Medical Center: collaborator
• Seoul National University Hospital: collaborator
• Seoul National University Bundang Hospital: collaborator

Study Sites (1)

National Cancer Center

Goyang-si, Gyeonggi-do, 410-769, South Korea

RECRUITING

Related Publications (1)

• Sim SH, Park IH, Jung KH, Kim SB, Ahn JH, Lee KH, Im SA, Im YH, Park YH, Sohn J, Kim YJ, Lee S, Kim HJ, Chae YS, Park KH, Nam BH, Lee KS, Ro J. Randomised Phase 2 study of lapatinib and vinorelbine vs vinorelbine in patients with HER2 + metastatic breast cancer after lapatinib and trastuzumab treatment (KCSG BR11-16). Br J Cancer. 2019 Dec;121(12):985-990. doi: 10.1038/s41416-019-0618-z. Epub 2019 Nov 6.

  PMID: 31690831 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Vinorelbine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Jungsil Ro

  National Cancer Center, Korea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jungsil Ro

CONTACT

+82-31-920-1910; jungsro@ncc.re.rk

Inhae Park

CONTACT

+82-31-920-1680; parkih@ncc.re.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Center for Clinical Trials

Study Record Dates

• First Submitted: July 15, 2012
• First Posted: November 21, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 12, 2014

Record last verified: 2014-03

Locations

KR (1)