Lapatinib in Combination With Docetaxel in Patients With HER-2 Positive Advanced or Metastatic Breast Cancer

NCT01044485 | Completed Phase 1 DMC

• 1 other identifier: 0205-1isni 07 / 001.112
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this phase I/ II study is therefore to assess the safety and efficacy of lapatinib in combination with docetaxel in patients with advanced cancer. Only patients in first line treatment for metastatic disease should be included in the present study. It is proposed to start with a phase I part evaluating the safety of lapatinib 1250 mg with docetaxel 75 mg/m² without systematic support of growth factors, starting after the completion and data from the 1000 mg lapatinib +75 mg/m² docetaxel dose level in the EORTC (Bonnefoi) study.The objective of the phase II part will confirm the safety and evaluate efficacy of lapatinib in combination with docetaxel.

Conditions

Metastatic Breast Cancer

Keywords

HER-2 positive advanced or metastatic breast cancer; dose escalation study; lapatinib; docetaxel

Outcome Measures

Primary Outcomes (1)

• To determine the optimal tolerated regimen of lapatinib administered in combination with docetaxel as first-line therapy in patients with metastatic breast cancer

  during first cycle ( each cycle last 3 weeks)

Secondary Outcomes (7)

• To evaluate the dose-limiting toxicity

  each weeks of each cycle and after the end of the study

• To evaluate anti-tumour activity in terms of response

  each cycle and at the end of the study

• To evaluate anti-tumour activity in time to response

  each cycle and at the end of the study

• To evaluate anti-tumour activity in terms of response duration

  each cycle and at the end of the study

• To evaluate anti-tumour activity, in terms time to progression (TTP)

  each cycle and at the end of the study

Study Arms (1)

lapatinib + docetaxel

OTHER

dose level Lapatinib (OD) Docetaxel (q3wks) Systematic Growth factor Minus 0 1250 mg 75 mg/m2 + systematic growth factor support 0, 1250mg 75 mg/m2 No +1 1500mg 75mg/m2 No Minus +1\* 1500mg 75mg/m2 + systematic growth factor support +2 1250mg 100mg/m2 No Minus +2\* + systematic growth factor support +3 1500mg 100mg/m2 No Minus +3\* + systematic growth factor support Apart within the minus dose levels, G-CSF support should be added only as rescue strategy if severe neutropenia occurred during the first cycle of studied dose.Patients will receive 4 cycles of the association. In case of benefit of the treatment, they should continue the treatment with lapatinib until progression.\* patients will be included at level "minus X" only if 2 DLT out of 6 patients based on febrile neutropenia occurred at level "X"

Drug: lapatinib; Drug: docetaxel

Interventions

lapatinib DRUG

escalation dose from 1250 to 1500 mg in association with docetaxel

lapatinib + docetaxel

docetaxel DRUG

escalation dose from 75 mg/m2 to 100 mg/m2 in association with lapatinib

lapatinib + docetaxel

Eligibility Criteria

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

You may qualify if:

• Age over or equal 18 years·
• ECOG Performance Status of 0 to 2·
• Patients with histological or cytological confirmed breast cancer, HER positive (IHC 3+, or IHC 2+ and FISH/CISH +, or FISH+ or CISH+ only), not amenable for an alternative curative strategy in first line metastatic setting·
• Patients who receive hormonotherapy for metastatic disease or who received chemotherapy in adjuvant setting if recurrence occur after 6 months are eligible·
• Patient must have not received the last injection of trastuzumab within the six weeks·
• Subjects must have completed prior radiotherapy treatment at least 4 weeks from enrolment and recovered from all treatment-related toxicities· Subjects must have tissue available to prospectively determine treatment assignment and to compare tumor response with intra-tumor expression levels of relevant biomarkers·
• No prior systemic investigational agent within the past 30 days or topical investigational drugs within the past 7 days·
• Subjects must have a cardiac ejection fraction within the institutional range of normal as measured by ECHO (echocardiogram) or MUGA (Multigated Acquisition) scan·
• Subjects must have adequate haematological, hepatic, and renal function·
• Affiliation to a social insurance program is required

You may not qualify if:

• Subjects with elevations of transaminase (ALT and/or AST) greater than 2.5 times the upper limit of the normal range (ULN) are NOT eligible for the study·
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier·
• Patients who have had prior treatment with EGFR targeting therapies· All herbal (alternative) medicines are excluded·
• Patients with known brain metastases·
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib.·
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, peripheral neuropathy of grade 2 or greater, or psychiatric illness/social situations that would limit compliance with study requirements·
• Pregnant women are excluded from this study because lapatinib is member of the 4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or abortifacient effects·
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib·
• Patients with gastro intestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, 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)· Previous allergic reaction to docetaxel and/or polyascorbate· Concomitant requirement for medication classified as CYP3A4 inducers or inhibitors·
• Active cardiac disease, defined as: history of uncontrolled or symptomatic angina pectoris, history of cardiac arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation, myocardial infarction \< 6 months from study entry, uncontrolled or symptomatic congestive heart failure, ejection fraction below the institutional normal limit

Sponsors & Collaborators

• Centre Georges Francois Leclerc: lead
• GlaxoSmithKline: collaborator
• Sanofi: collaborator

Study Sites (1)

Centre Georges François Leclerc

Dijon, Bourgogne-Franche-Comté, 21000, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Docetaxel

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Nicolas Isambert, MD

  Centre Georges François Leclerc

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 5, 2010
• First Posted: January 8, 2010
• Study Start: November 1, 2008
• Primary Completion: November 1, 2011
• Last Updated: September 25, 2012

Record last verified: 2012-09

Locations

FR (1)