Study of Foretinib in Combination With Lapatinib in Patients With Metastatic Breast Cancer

NCT01138384 | Completed Phase 1 DMC

• 1 other identifier: I198
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 5

Brief Summary

This research is being done because it is not yet known what dose of foretinib in combination with lapatinib can be given safely to patients with breast cancer, nor what type and severity of side effects will result from the combination of the two treatments. This research is also being done because it is not clear if the addition of the new drug foretinib to treatment with lapatinib can offer better results and longer survival than treatment with lapatinib alone.

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Toxicity, maximum administered dose and the recommended phase II dose

  Adverse events will be graded using CTCAE V4.0

  every 4 weeks

Secondary Outcomes (2)

• Pharmacokinetic evaluation of lapatinib

  cycle 1 only

• Preliminary evidence of efficacy

  every 8 weeks

Study Arms (1)

Foretinib and Lapatinib

EXPERIMENTAL

Patients will receive foretinib as a continuous oral dose, and lapatinib as a continuous oral dose. Lapatinib will commence on Day1, Cycle 1 and foretinib will commence on Day 3, Cycle 1.

Drug: Foretinib; Drug: Lapatinib

Interventions

Foretinib DRUG

Daily oral dosing at assigned dose beginning day 3 of cycle 1

Foretinib and Lapatinib

Lapatinib DRUG

Daily oral dosing at assigned dose beginning day 1 cycle 1.

Foretinib and Lapatinib

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of invasive breast cancer, that is human epidermal growth factor receptor 2 (HER2) positive assessed by FISH or IHC 3+ staining (in accordance with ASCO guidelines) on the basis of the local evaluation of HER2 status.
• Formalin fixed paraffin embedded tissue available for translational studies. Patients entered on the expanded RP2D cohort must have an accessible tumour lesion for biopsy.
• Advanced or recurrent/ metastatic disease incurable with standard therapies.
• During the dose escalation phase patients are not required to have measurable disease, but if they do, it will be recorded and followed. Patients at the expanded RP2D must have measurable disease defined by the RECIST 1.1.
• ECOG performance status 0, 1 or 2.
• Age ≥ 18 years of age.
• Any treatment-related major organ toxicities must be recovered to ≤ grade 1.
• Patients may have had prior chemotherapy for adjuvant and/or for metastatic disease. There is no limit to the number of previous chemotherapy regimens allowed provided patients meet other eligibility criteria. A minimum of 21 days since the last dose of chemotherapy must have elapsed prior to registration.
• Patients may have had prior hormone therapy. There is no limit to the number of previous hormone regimens allowed provided patients meet other eligibility criteria. A minimum of 7 days since the last dose of hormone therapy must have elapsed prior to registration.
• Patients may have had prior therapy with trastuzumab or lapatinib. No prior therapy with a c-Met inhibitor or angiogenesis inhibitor. Other targeted agents permissible provided a minimum of 21 days has elapsed since last day of targeted therapy and registration.
• Patients may have had prior radiation therapy provided the patient has recovered from acute toxic effects of the radiation therapy prior to registration and at least 21 days have elapsed from the day of the last fraction of radiation to the date of registration.
• Previous surgery is permitted provided that wound healing has occurred and at least 14 days have elapsed prior to registration if surgery was major.
• Granulocytes (AGC) ≥ 1.5 x 109/L; Platelets ≥ 100 x 109/L
• Serum creatinine ≤ 1.2 x UNL; Total bilirubin ≤ 1.2 x UNL; AST and ALT ≤ 2 x UNL; Potassium within normal range; Magnesium within normal range
• Left ventricular ejection fraction ≥ 50% demonstrated by MUGA scan or echocardiogram within 28 days prior to registration.

You may not qualify if:

• History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
• Resting BP consistently higher than, systolic \> 150 mmHg and/or diastolic \> 100 mmHg (in the presence or absence of a stable dose of anti-hypertensive medication) or poorly controlled hypertension, history of labile hypertension or poor compliance with anti-hypertensive medication.
• Appreciable cavitating or actively bleeding lesions.
• Untreated brain or meningeal metastases. (Patients with neurologically stable and treated brain metastases who have discontinued corticosteroids at least two weeks prior to study registration and have no evidence of cavitation or hemorrhage are eligible).
• Serious cardiac illness or condition including, but not limited to:
• history of documented congestive heart failure (CHF)
• systolic dysfunction (LVEF \< 50% by MUGA or ECHO)
• high risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately rate-controlled)
• unstable angina pectoris requiring anti-anginal medication
• clinically significant valvular heart disease
• evidence of transmural infarction on ECG
• New York Heart Association (NYHA) Class III or IV functional status (see Appendix VIII)
• Patients with QTc \> 450 msec are not eligible
• GI tract disease resulting in an inability to absorb oral medication
• Active or uncontrolled infections, or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol are not eligible.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• GlaxoSmithKline: collaborator

Study Sites (5)

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (1)

• Chia SK, Ellard SL, Mates M, Welch S, Mihalcioiu C, Miller WH Jr, Gelmon K, Lohrisch C, Kumar V, Taylor S, Hagerman L, Goodwin R, Wang T, Sakashita S, Tsao MS, Eisenhauer E, Bradbury P. A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer. Breast Cancer Res. 2017 May 2;19(1):54. doi: 10.1186/s13058-017-0836-3.

  PMID: 28464908 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

GSK 1363089; Lapatinib

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

Study Officials

• Stephen Chia

  British Columbia Cancer Agency

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 4, 2010
• First Posted: June 7, 2010
• Study Start: October 27, 2010
• Primary Completion: May 14, 2014
• Study Completion: February 13, 2015
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)