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PostmenopausalPhase 2OLYMPENCT02322853

A Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors

A Phase 2 study testing Tamoxifen and Ralimetinib (LY2228820 dimesylate) in people with Postmenopausal and Metastatic Breast Cancer, run by Centre Francois Baclesse at 14 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Metastatic breast cancer (MBC) remains an incurable disease and despite an improvement of the effect of systemic treatments. After relapse on first-line non-steroidal aromatase inhibitor, current clinical practice and treatment guidelines include tamoxifen, fulvestrant (an ER antagonist) and exemestane as available… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Postmenopausal, Metastatic Breast Cancer
What is being tested?
Tamoxifen and Ralimetinib (LY2228820 dimesylate)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
14 sitesFrance
Study dates
Jan 2015to Apr 2017
Phase
Phase 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

  • Women with histologically confirmed breast cancer
  • 18 < age < 80 years old
  • Menopausal status Women are considered post-menopausal and not of child bearing potential if they have had
  • 12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or
  • 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or
  • surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
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  • ER-positive status by local laboratory testing (>10% by IHC) and HER2-negative status (IHC 0 or 1+ or 2+ and FISH negative) on the last biopsy or surgical specimen available.
  • Disease progression defined as inoperable locally advanced or metastatic breast cancer (MBC) excluding aggressive visceral disease requiring other approaches, such as chemotherapy
  • Disease refractory to aromatase inhibitors (AI) defined as:
  • recurrence while on, or within 12 months of end of adjuvant treatment with aromatase inhibitor, or
  • progression while on, or within 3 months of end of AI for locally advanced or MBC
  • Patients who have received fulvestrant are eligible
  • Maximum 2 previous lines of chemotherapy for MBC
  • Performance Status (PS) ≤ 2
  • Patient able to swallow and retain oral medication
  • Measurable or evaluable lesions as per RECIST 1.1
  • Measurable disease (≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography scan) or
  • Non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
  • Patients with only pleural effusion and/or ascites are not eligible.
  • Adequate bone marrow and organ function as defined by the following laboratory values:
  • Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
  • Platelets (plt) ≥ 100 x 109/L
  • Hemoglobin (Hgb) ≥ 9 g/dl
  • INR ≤ 1.5 without any anticoagulation treatment
  • Serum creatinine ≤ 1.5 x ULN
  • Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) within normal range (or < 3.0 x ULN if liver metastases are present)
  • Total serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome, which is defined as presence of several episodes of unconjugated hyperbilirubinemia with normal results from CBC count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis
  • Patient has signed informed consents obtained before any trial related activities and according to local guidelines

Who cannot join

  • • Previous treatment with p38 MAPK inhibitors or Tamoxifen in metastatic setting (adjuvant treatment by tamoxifen is allowed)
  • More than 2 lines of chemotherapy for locally advanced and/or metastatic breast cancer
  • Brain metastasis
  • Other malignancy (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer).
  • Clinically significant (i.e. active) cardiovascular disease: cerebro-vascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; CHF of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication.
  • Have had a major bowel resection that would alter oral drug absorption.
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  • Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis).
  • Are receiving concurrent administration of immunosuppressive therapy
  • Concurrent participation in any therapeutic clinical trial
  • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

France14 sites

  • Institut Bergonié

    Bordeaux

  • Centre François Baclesse

    Caen

  • Centre Jean Perrin

    Clermont-Ferrand

  • Centre Georges-François Leclerc

    Dijon

  • Centre Léon Bérard

    Lyon

  • Institut Paoli Calmettes

    Marseille

  • Institut de Cancérologie de l'Ouest

    Nantes

  • Hegp, Ap-Hp

    Paris

  • Hôpital St Louis, AP-HP

    Paris

  • Centre Eugène Marquis

    Rennes

  • Centre Henri Becquerel

    Rouen

  • Institut Curie

    Saint-Cloud

  • Institut Claudius Regaud

    Toulouse

  • Institut Gustave Roussy

    Villejuif

Other trials in France

About this study

Official title: A Randomized Open-label Phase II Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors

Metastatic breast cancer (MBC) remains an incurable disease and despite an improvement of the effect of systemic treatments. After relapse on first-line non-steroidal aromatase inhibitor, current clinical practice and treatment guidelines include tamoxifen, fulvestrant (an ER antagonist) and exemestane as available options (NCCN treatment guidelines 2012), but in this context of resistance, their efficacy are poor.

Some results confirm the possibility to improve the efficacy of tamoxifen in metastatic setting by a combination with therapy targeting signal transduction pathways. Other transduction pathways seem to be involved in endocrine sensitivity/resistance, such as RAS/RAF/MEK/MAK pathway.

LY2228820 inhibits the activity of p38 MAPK (selective inhibitor of the α and β isoforms of p38 MAPK in vitro) and reduces phosphorylation of its cellular target, MAPK-activated protein kinase 2 (MAPKAP-K2).

Being tested
Tamoxifen, Ralimetinib (LY2228820 dimesylate)
Keywords
Metastatic breast cancer, p38 map kinase, tamoxifen, LY2228820, Postmenopausal woman with advanced or metastatic breast cancer progressing on aromatase inhibitors (AI)
Medical subject headings
Breast Neoplasms

What participants receive

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

  • TamoxifenDrug

    hormonotherapy

  • Ralimetinib (LY2228820 dimesylate)Drug

    Also called target therapy

Study groups in NCT02322853
Study groupRoleWhat they receive
TAMOXIFENActive comparatorTamoxifen will be administered daily orally Patients will receive study medication until disease progression or unacceptable toxicity
Receives: Drug: Tamoxifen
TAMOXIFEN + LY2228820ExperimentalTamoxifen will be administered daily orally LY2228820 dimesylate (Ralimetinib) will be administered orally Patients will receive study medication until disease progression or unacceptable toxicity
Receives: Drug: Tamoxifen; Drug: Ralimetinib (LY2228820 dimesylate)

What is being measured

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

  1. To define the efficacy (progression-free survival rate at 6 months) of LY2228820 in combination with tamoxifen for postmenopausal women with an ER positive and HER2 negative advanced or metastatic breast cancer who progressed on aromatase inhibitors.

    Measured: at 6 months after treatment start.

Secondary outcomes (4)

  1. - To evaluate the toxicity profile (Safety and Tolerability) of the LY2228820 in combination with tamoxifen

    Adverse events description and grade in all participants

    Measured: From date of randomization until study participation (during average 12 months)

  2. - To estimate the Progression-Free Survival of the LY2228820 in combination with tamoxifen

    Measured: evaluated every 8-12 weeks (during average 12 months)

  3. - To assess the overall survival of the LY2228820 in combination with tamoxifen

    Measured: From date of randomization until the date of first documented date of death from any cause, whichever came first, assessed up to 60 months

  4. - To assess response duration of the LY2228820 in combination with tamoxifen

    Measured: evaluated every 8-12 weeks during treatment to progression or death for any cause.(during average 12 months)

Timeline

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

  1. First posted23 Dec 2014 (estimated)
  2. Study startJan 2015
  3. Primary completionApr 2017
  4. Study completionApr 2017

Why it stopped: lack of recruitment

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02322853
Sponsor's protocol ID
OLYMPE / 2013-005084-29
Acronym
OLYMPE
Status last verified
May 2017
First submitted
12 Dec 2014
Last updated
24 May 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tamoxifen and Ralimetinib (LY2228820 dimesylate) in people with Postmenopausal and Metastatic Breast Cancer, run by Centre Francois Baclesse at 14 sites in France.

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 28 inclusion and 10 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: stopped early, as of the sponsor's last update on 24 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in France. 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 phase mean?

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 was stopped early (reason given: lack of recruitment). Results are not available in the source record.

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?

To define the efficacy (progression-free survival rate at 6 months) of LY2228820 in combination with tamoxifen for postmenopausal women with an ER positive and HER2 negative advanced or metastatic breast cancer who progressed on aromatase inhibitors. (time frame: at 6 months after treatment start.). 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 NCT02322853.

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 24 May 2017.

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