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

NCT02322853 | Terminated Phase 2 DMC

• 1 other identifier: OLYMPE / 2013-005084-29
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 14

Brief 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 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).

Conditions

Postmenopausal; Metastatic Breast Cancer

Keywords

Metastatic breast cancer; p38 map kinase; tamoxifen; LY2228820; Postmenopausal woman with advanced or metastatic breast cancer progressing on aromatase inhibitors (AI)

Outcome Measures

Primary Outcomes (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.

  at 6 months after treatment start.

Secondary Outcomes (4)

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

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

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

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

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

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

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

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

Study Arms (2)

TAMOXIFEN

ACTIVE COMPARATOR

Tamoxifen will be administered daily orally Patients will receive study medication until disease progression or unacceptable toxicity

Drug: Tamoxifen

TAMOXIFEN + LY2228820

EXPERIMENTAL

Tamoxifen will be administered daily orally LY2228820 dimesylate (Ralimetinib) will be administered orally Patients will receive study medication until disease progression or unacceptable toxicity

Drug: Tamoxifen; Drug: Ralimetinib (LY2228820 dimesylate)

Interventions

Tamoxifen DRUG

hormonotherapy

TAMOXIFEN; TAMOXIFEN + LY2228820

Ralimetinib (LY2228820 dimesylate) DRUG

Also known as: target therapy

TAMOXIFEN + LY2228820

Eligibility Criteria

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

You may qualify if:

• Women with histologically confirmed breast cancer
• \< age \< 80 years old
• Menopausal status Women are considered post-menopausal and not of child bearing potential if they have had
• months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or
• 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
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Centre Francois Baclesse: lead
• National Cancer Institute, France: collaborator
• ARC Foundation for Cancer Research: collaborator

Study Sites (14)

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Georges-François Leclerc

Dijon, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Institut de Cancérologie de l'Ouest

Nantes, France

Location

Hegp, Ap-Hp

Paris, France

Location

Hôpital St Louis, AP-HP

Paris, France

Location

Centre Eugène Marquis

Rennes, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Curie

Saint-Cloud, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen; ralimetinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Christelle LEVY, MD

  c.levy@baclesse.unicancer.fr

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2014
• First Posted: December 23, 2014
• Study Start: January 1, 2015
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: May 24, 2017

Record last verified: 2017-05

Locations

FR (14)