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Breast CancerPhase 1/2NCT01138384

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

A Phase 1/2 study testing Foretinib and Lapatinib in people with Breast Cancer, run by NCIC Clinical Trials Group at 5 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Foretinib and Lapatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
5 sitesCanada
Study dates
27 Oct 2010to 13 Feb 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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 2 working days of patient registration.

Who cannot join

  • 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)
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  • 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.
  • 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.
  • Patients on treatment with agents with a known risk of Torsades de Pointes (List #1 http://torsades.org) are not eligible.
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Canada5 sites

  • BCCA - Cancer Centre for the Southern Interior

    Kelowna, British Columbia, V1Y 5L3

  • Cancer Centre of Southeastern Ontario at Kingston

    Kingston, Ontario, K7L 5P9

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • McGill University - Dept. Oncology

    Montreal, Quebec, H2W 1S6

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase I/II Study of Foretinib in Combination With Lapatinib in Patients With Human Epidermal Growth Factor Receptor 2(HER2)Over-Expressing Metastatic Breast Cancer

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.

Read the detailed description

The purpose of this study is to find the dose of foretinib that can safely be given in combination with lapatinib. This is done by starting at doses of both drugs lower than the usual doses of each when given on their own. Patients are given foretinib and lapatinib and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then more patients are asked to join the study and are given higher does of foretinib and lapatinib. Patients joining the study later on will get higher doses of foretinib and lapatinib than patients who join earlier. This will continue until a dose is found that causes severe but temporary side effects. Doses higher than that will not be given.

Conditions
Breast Cancer
Being tested
Foretinib, Lapatinib
Keywords
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ForetinibDrug

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

  • LapatinibDrug

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

Study groups in NCT01138384
Study groupRoleWhat they receive
Foretinib and LapatinibExperimentalPatients 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.
Receives: Drug: Foretinib; Drug: Lapatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity, maximum administered dose and the recommended phase II dose

    Adverse events will be graded using CTCAE V4.0

    Measured: every 4 weeks

Secondary outcomes (2)

  1. Pharmacokinetic evaluation of lapatinib

    pharmacokinetic evaluation of lapatinib when administered in combination with foretinib

    Measured: cycle 1 only

  2. Preliminary evidence of efficacy

    All patients with measurable disease will be evaluated for response and progression using RECIST 1.1.

    Measured: every 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2010 (estimated)
  2. Study start27 Oct 2010
  3. Primary completion14 May 2014
  4. Study completion13 Feb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01138384
Sponsor's protocol ID
I198
Status last verified
Apr 2020
First submitted
4 Jun 2010
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 28464908

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Foretinib and Lapatinib in people with Breast Cancer, run by NCIC Clinical Trials Group at 5 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity, maximum administered dose and the recommended phase II dose (time frame: every 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01138384, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.

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