A Study of Foretinib in Patients With Recurrent/Metastatic Breast Cancer (IND197)

A Phase II Study of Foretinib in Patients With Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) Negative, Recurrent/Metastatic Breast Cancer

The purpose of this study is to find out what effects this new drug foretinib has on this type of breast cancer, called "triple negative" breast cancer because the cancer tissue is estrogen, progesterone and HER2 receptor negative.

Study Overview

• Status: Completed
• Conditions: Recurrent Breast Cancer
• Intervention / Treatment: Drug: Foretinib

Detailed Description

This research is being done because there is no treatment that will cure this type of cancer. Although some types of chemotherapy can cause this cancer to shrink for a time, better options are needed.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • BCCA - Cancer Centre for the Southern Interior
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Health Research Institute - General Division
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles LeMoyne
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of invasive breast cancer, that is estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER2) negative.
• Formalin fixed paraffin embedded tissue available for central pathology review and translational studies. Patients entered on the second stage of accrual must have an accessible tumour lesion for biopsy.
• Advanced or recurrent/ metastatic disease incurable with standard therapies.
• Clinically and/or radiologically documented measurable disease. At least one site of disease must be unidimensionally measurable.
• ECOG performance of 0, 1 or 2.
• Age ≥ 18 years of age.
• Previous Therapy: Any treatment-related major organ toxicities must be recovered to ≤ grade 1.
• Patients may have received adjuvant chemotherapy and/or one prior line of chemotherapy in the recurrent/metastatic setting. A minimum of 21 days since the last dose of chemotherapy must have elapsed prior to registration.
• No prior therapy with a c-Met inhibitor or angiogenesis inhibitor. Other targeted agents are permissible provided a minimum of 21 days has elapsed since last day of targeted therapy and registration.
• Prior radiation therapy permitted 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. Exceptions may be made for non-myelosuppressive radiation to peripheral areas.
• Previous surgery permitted provided wound healing has occurred and at least 14 days have elapsed 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; ALT and AST ≤ 2 x UNL
• Women must be post menopausal, surgically sterile or use a reliable form of contraception while on study and for 90 days after discontinuing therapy. Women of childbearing potential must have a pregnancy test taken and proven negative within 7 days prior to registration and must not be lactating.
• Patients who require oral anticoagulants (coumadin, warfarin) are eligible
• Patient consent must be obtained according to local Institutional and/or University Human Experimentation Committee requirements.
• Protocol treatment must begin within 7 working days of patient registration.

Exclusion Criteria:

• 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).
• Untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction. Patients with a significant cardiac history (even if controlled) or prior anthracycline exposure are required to have an LVEF > 50%.
• 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.
• Known hypersensitivity to the study drugs or their components.
• Potent CYP3A4 inhibitors/inducers (e.g. ketoconazole, carbamazepine) must be discontinued at least 7 days prior to Day 1, Cycle 1.
• Treatment, concurrent or within 3 weeks prior to registration, with other investigational drugs or anti-cancer therapy.
• Proliferative diabetic retinopathy, retinal arteritis or hemorrhage.
• History of pulmonary embolus or a deep vein thrombosis diagnosed and/or treated within 6 months prior to registration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Foretinib	Drug: Foretinib; foretinib, at a continuous oral daily dose of 60 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response and early progression rate	All patients will be assessed for response at the end of every second cycle (every 8 weeks). Response and progression will be evaluated using RECIST 1.1.	Every 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events as a Measure of Safety and Tolerability	All patients will be assessed for toxicity at the end of every cycle (every 4 weeks). Adverse events will be graded using CTCAE V4.0.	every 4 weeks
Relationship between response and biomarkers	Archival tissue will be collected on all patients. Pre-treatment fresh tissue biopsies CTC's will be collected on all patients entered in the second stage of accrual. Translational research studies will be done as described in protocol section 17.0.	2 years (end of study)
Biomarkers in Tumour cells	Archival tissue will be collected on all patients. Pre-treatment fresh tissue biopsies CTC's will be collected on all patients entered in the second stage of accrual. Translational research studies will be done as described in protocol section 17.0.	2 years (end of study)

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: GlaxoSmithKline
• Investigators: Study Chair: Sasha Lupichuk, Tom Baker Cancer Centre, Calgary AB; Study Chair: Daniel Rayson, QEII HSC - Nova Scotia Cancer Centre

Publications and helpful links

General Publications

• Rayson D, Lupichuk S, Potvin K, Dent S, Shenkier T, Dhesy-Thind S, Ellard SL, Prady C, Salim M, Farmer P, Allo G, Tsao MS, Allan A, Ludkovski O, Bonomi M, Tu D, Hagerman L, Goodwin R, Eisenhauer E, Bradbury P. Canadian Cancer Trials Group IND197: a phase II study of foretinib in patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-negative recurrent or metastatic breast cancer. Breast Cancer Res Treat. 2016 May;157(1):109-16. doi: 10.1007/s10549-016-3812-1. Epub 2016 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2010
• Primary Completion (Actual): December 14, 2014
• Study Completion (Actual): February 13, 2015

Study Registration Dates

• First Submitted: May 27, 2010
• First Submitted That Met QC Criteria: June 18, 2010
• First Posted (Estimated): June 22, 2010

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Breast Neoplasms; Recurrence
• Other Study ID Numbers: I197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No