Lapatinib in Combination With Vinorelbine

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01013740
• Date of registration: 29/10/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Lapatinib in Combination With Vinorelbine VITAL
• Scientific title: A Phase II, Randomised, Multi-Centre Study Evaluating Lapatinib in Combination With Vinorelbine or Capecitabine in Women With ErbB2 Overexpressing Metastatic Breast Cancer
• Date of first enrolment: November 25, 2009
• Target sample size: 112
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01013740
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Bulgaria, Chile, France, Germany, Greece, Italy, Mexico, Poland, Serbia, Spain

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria :

- Signed informed consent prior to registration.

- Considered by the investigator to have a life expectancy of =12 weeks.

- Subjects must be female and have histologically - confirmed invasive breast cancer
with Stage IV disease at primary diagnosis or at relapse after curative - intent
surgery.

- Documented overexpression of ErbB2

- Subjects should have progressive disease following prior therapy which may include
anthracyclines, taxanes, and trastuzumab.

- Females aged =18 years

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.

- Subjects must have adequate organ and marrow function

- Subjects must have a cardiac ejection fraction of at least 50% and within the
institutional range of normal.

- Radiotherapy prior to initiation of study medication is allowed to a limited area ( e
. g . , palliative therapy ) , if it is not the sole site of disease.

- Subjects with stable central nervous system (CNS) metastases are permitted.

- Subject must be free of gastrointestinal diseases or any other conditions that impede
swallowing, retaining, and absorption of oral medications.

- Bisphosphonate therapy for bone metastases is allowed; however, treatment must be
initiated prior to the first dose of study medication. Prophylactic use of
bisphosphonates in subjects without bone disease, except for the treatment of
osteoporosis, is not permitted.

Exclusion Criteria:

- Subjects taking prohibited medications are not eligible for the study.

- Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this
study.

- Prior therapy with more than one chemotherapeutic regimen for metastatic breast
cancer.

- Concurrent anticancer or concomitant radiotherapy treatment.

- History of uncontrolled or symptomatic angina; history of arrhythmias requiring
medications ; clinically significant myocardial infarction < 6 months from study
entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below
the institutional normal limit; or any other cardiac condition, which in the opinion
of the treating physician, would make this protocol unreasonably hazardous for the
patient.

- Have 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).

- Use of an investigational drug within 30 days or 5 half - lives, whichever is longer,
preceding the first dose of investigational treatment, or, concurrent treatment with
an investigational agent or participation in another clinical trial involving
investigational agents.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to any of the agents used in this study or their excipients that in
the opinion of the investigator or GSK Medical Monitor contraindicates their
participation.

- Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD).

- Known history of uncontrolled inter - current illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, clinically significant cardiac arrhythmia, or psychiatric illness / social
situations that would limit compliance with study requirements.

- Concurrent disease or condition that would make the subject inappropriate for study
participation , or any serious medical disorder that would interfere with the
subject's safety.

- Pregnant or lactating females at any time during the study (due to the potential
teratogenic or abortifacient effects of lapatinib and breastfeeding).

- Subjects with diseases affecting gastrointestinal function resulting in an inability
to take oral medication , including ; malabsorption syndrome, disease significantly
affecting gastrointestinal function , or resection of the stomach , small bowel , or
colon. Subjects with inflammatory bowel disease or ulcerative colitis are also
excluded.

- Peripheral neuropathy of Grade 2 or greater.

- Unresolved or unstable, serious toxicity from prior administration of another
investigational drug and / or of prior cancer treatment.

- Dementia, altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Cancer

Intervention(s)

Drug: Capecitabine

Drug: Vinorelbine

Drug: Lapatinib

Primary Outcome(s)

Progression Free Survival (PFS) in the Randomized Phase [Time Frame: From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)]

Secondary Outcome(s)

Maximum Concentration (Cmax) for Vinorelbine [Time Frame: Days 1 and 8; 0 to 24 hours post-dose]

Overall Survival (OS) [Time Frame: From the date of randomization until death (average of 55 study weeks)]

Time to Response in the Randomized Phase [Time Frame: From randomization until the time of the first documented confirmed CR or PR (average of 27 study weeks)]

Area Under the Concentration-time Curve Over the Dosing Interval (AUC-tau) for Vinorelbine [Time Frame: Days 1 and 8; 0 to 24 hours post-dose]

Duration of Response (DOR) in the Randomized Phase [Time Frame: From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 27 study weeks)]

Number of Participants With Grade 4 and Grade 5 Adverse Events (AE) [Time Frame: From randomization until disease progression, death, or discontinuation from the study (average of 55 study weeks)]

Number of Participants With Clinical Benefit (CB) in the Randomized Phase [Time Frame: From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)]

Number of Participants With Overall Response (OR), as Assessed by the Investigator in the Randomized Phase [Time Frame: From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)]

Secondary ID(s)

CLAP016A2205 / 112620

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/07/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01013740