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Trial details
A Phase II Study of Ovarian Function Suppression And ExemesTane with or without PalbocIclib in PreMenopausal Women with ER positive / HER-2 negative MetAstatic Breast Cancer (FATIMA)
Current status:
Approved
|
Date registered:
05/03/2019
Trial version(s)
Current: 03/01/2019
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Main Information
Primary registry identifying number
LBCTR2019020181
Protocol number
AMCI – 001
MOH registration number
2018/2/51295
Trial already registered with the MoPH
Study registered at the country of origin
Not registered
Type of registration
Prospective
Date of registration in national regulatory agency
03/01/2019
Primary sponsor
AMCI (Africa Middle East Cancer Intergroup)/Investigator Initiated Research
Primary sponsor: Country of origin
Lebanon
Public title
A Phase II Study of Ovarian Function Suppression And ExemesTane with or without PalbocIclib in PreMenopausal Women with ER positive / HER-2 negative MetAstatic Breast Cancer (FATIMA)
Acronym
FATIMA
Scientific title
A Phase II Study of Ovarian Function Suppression And ExemesTane with or without PalbocIclib in PreMenopausal Women with ER positive / HER-2 negative MetAstatic Breast Cancer
Acronym
Brief summary of the study: English
This is an open label, randomized, multicenter, international phase II study for premenopausal patients with hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. Randomization will be done in a 1:1 ratio. Patients will be randomized to receive either palbociclib + exemestane + OFS (Arm A) or exemestane +OFS (Arm B). Treatment will be continued until disease progression, unacceptable toxicities, or withdrawal of consent.
Brief summary of the study: Arabic
هذه دراسة دولية، مفتوحة التسمية، عشوائية، متعددة المراكز وفي المرحلة الثانية لنساء لم يدخلن في سن اليأس ومصابات بسرطان ثدي نقيلي متقدم موضعياً أو إيجابي لمستقبلات الإستروجين و سلبي لمستقبلات العامل البشري لنمو البشرة – 2. سيتم التوزيع العشوائي بنسبة 1:1 . سيتم توزيع المرضى عشوائياً لتلقي إما تعطيل وظيفة المبيض+ الإكسيميستان+ البالبوسيكليب (طريقة العلاج 1) أو تعطيل وظيفة المبيض+ الإكسيميستان (طريقة العلاج .(2 سيستمر أخذ العلاج إلى حين تفاقم المرض أو الإصابة بتسمم حاد أو سحب الموافقة.
Health conditions/problem studied: Specify
Metastatic Breast Cancer – Oncology
Interventions: Specify
MEDICINAL PRODUCT{S}: Palbociclib
Key inclusion and exclusion criteria: Inclusion criteria
Subjects must meet all the following inclusion criteria to be eligible for enrolment into the study: 1. Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer (histologically or cytologically proven diagnosis of adenocarcinoma of the breast) not amenable to curative treatment by surgery or radiotherapy. 2. ER positive tumour: Histological or cytological confirmation of estrogen and/or progesterone-receptor positive, as determined by routine IHC. Positivity is defined as ≥1% positive stained cells. The receptor status determined by utilizing an assay consistent with local laboratory standards. 3. HER2 negative breast cancer as confirmed by IHC, SISH or FISH. 4. Premenopausal women : (definition of a real menopause is not a simple task in these relatively young women, owing to the potential effect of prior chemotherapy and /or endocrinal therapy particularly OFS) defined either by: i. Any age below 40 years , irrespective to E2 level or menstrual history ii. If the woman had a menstrual period any time within the last 12 months iii. If the woman has amenorrhea of more than 12 months (in the absence of chemotherapy or ovarian function suppression) that is associated with serum hormone levels that are NOT in the postmenopausal range (either estradiol (E2) < 30 pg/mL and follicle-stimulating hormone (FSH) < 20 mU/mL OR E2 ≥ 30 pg/mL and FSH ≥ 20 mU/mL) [30]. 5. Secondary hormonal resistance to tamoxifen or endocrinal sensitive metastatic disease i. Secondary hormonal resistance is defined as recurrence after 24 months from the start of adjuvant tamoxifen treatment or within 12 months from the end of the 5 years of adjuvant Tamoxifen ii. Endocrinal sensitive disease is defined as recurrence after 12 months from the end of adjuvant tamoxifen treatment or de novo metastatic disease 6. Measurable disease according to RECIST or bone-only metastases. Previously irradiated lesions are deemed measurable only if progression is documented at the site after completion of radiation. i. Patients must either have at least one lesion that can be accurately measured; OR ii. Patients have bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above. 7. ECOG Performance Status 0, 1, & 2. 8. Resolution of all acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade 1 (except alopecia or other toxicities not considered a safety risk for the patient). 9. Adequate organ function as defined by the following criteria: i. Absolute neutrophil count (ANC) ≥ 1.5 109/L ii. Platelets > 100 x109/L iii. Hemoglobin (Hgb) > 9.0g/dL iv. INR < 2 v. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x ULN (or <5 if hepatic metastases are present) vi. Total serum bilirubin < 1.5 x ULN (<3 x ULN for patients known to have Gilberts Syndrome) vii. Serum creatinine < 1.5 x ULN viii. QTc< 470 msec (based on the mean value of the triplicate ECGs). 10. Written informed consent obtained before any trial related activity and according to local guidelines.
Key inclusion and exclusion criteria: Gender
Female
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
Subjects presenting with any of the following will not be included in the study: 1. Postmenopausal women. Postmenopausal status is defined by age>40years with amenorrhea of more than 12 months, associated with serum hormonal levels of the postmenopausal range (either estradiol (E2) < 30 pg/mL and follicle-stimulating hormone (FSH) < 20 mU/mL or E2 ≥ 30 pg/mL and FSH ≥ 20 mU/mL) [30], in the absence of chemotherapy, tamoxifen, or OFS. 2. Patients with primary endocrinal resistance, defined as recurrence within 24 months from the start of adjuvant tamoxifen treatment. 3. Symptomatic and/or life threatening visceral metastases 1. Diffuse lymphangitic carcinomatosis. 2. Bulky liver or pulmonary metastases 4. Patients with only non-measurable lesions other than bone metastasis as defined above (e.g., pleural effusion, ascites, etc.). 5. Patients who have received hormonal treatment other than neo/adjuvant tamoxifen ± LHRH agonist for their early breast cancer. 6. Patients who received prior chemotherapy for metastatic or recurrent breast cancer. 7. Another malignancy within 5 years prior to enrolment with the exception of adequately treated in-situ carcinoma of the cervix, uterus, basal or squamous cell carcinoma or non-melanomatous skin cancer. 8. Uncontrolled (clinically or radiologically progressive) CNS metastases, carcinomatous meningitis, or leptomeningeal disease. 9. Major surgery within 3 weeks of first study treatment. 10. Chemotherapy, radiotherapy, or other anti-cancer therapy within 2 weeks before randomization. Patients who previously received radiotherapy to 25% of bone marrow are not eligible independent of when it was received. 11. Current treatment with any anti-cancer therapies for advanced disease; any experimental treatment of another clinical trial; therapeutic doses of anticoagulant. N.B. Low dose anticoagulants for deep vein thrombosis prophylaxis are allowed. Low molecular weight heparin is allowed. Aspirin is permitted. 12. Active bleeding diathesis. 13. History of non-compliance to medical regimens. Patients unwilling to or unable to comply with the protocol. 14. Pregnant or breast feeding women or those who are not using effective birth control methods. Adequate contraceptives must be used throughout the trial and for 8 weeks after the last study drug administration. Patients must have a negative serum pregnancy test within 7 days prior to first administration of study drug. 15. Prior hematopoietic stem cell or bone marrow transplantation. 16. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval. 17. Known or possible hypersensitivity to goserelin during the adjuvant setting. 18. Any severe and/or uncontrolled medical conditions such as: i. Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction < 6months prior to enrollment, serious uncontrolled cardiac arrhythmia ii. Uncontrolled diabetes as defined by fasting serum glucose > 3 x ULN iii. Acute and chronic active infectious disorders (except for Hepatitis B and Hepatitis C positive patients) and non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy iv. Known human immunodeficiency virus infection v. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Open (masking not used)
Study design: Control
Active
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
Yes, Lebanon and Worldwide
IMP has market authorization: Specify the countries
USA
Name of IMP
MEDICINAL PRODUCT{S}: Palbociclib
Year of authorization
2015
Month of authorization
1
Type of IMP
Others
Type of IMP: Specify
Cyclin-dependent kinase (CDK) inhibitor
Pharmaceutical class
Cyclin-dependent kinase (CDK) inhibitor
Therapeutic indication
Metastatic Breast Cancer – Oncology
Therapeutic benefit
There is a strong in-vitro and clinical evidence suggesting that the dual inhibition of CDK 4/6 and ER signaling is a highly effective therapeutic strategy in HR+ MBC. With the unprecedented success of palbociclib in PALOMA-1 trial, several phase 2 and 3 trials are underway to evaluate this agent (and other CDK4/6 inhibitors as well) in the different clinical scenarios of HR+ breast cancer [28].The vast majority of these trials –if not all– are testing these novel agents in postmenopausal patients, which would render the clinical experience of these agents restricted to postmenopausal women (median age was 62 years in PALOMA-1 trial) The scarcity of clinical trials addressing endocrinal therapy in premenopausal women with MBC is, at least in part, related to the fact that the majority of women in western countries are diagnosed with breast cancer during their postmenopausal life. However the situation is rather different in many countries, including those in the Middle East region, where the median age of women diagnosed with breast cancer is below 50 years, and where approximately 50% of these patients are still menstruating. This study will be the first to explore the therapeutic effects of palbociclib when combined with exemestane and ovarian function suppression (OFS) in premenopausal with hormone receptor positive and HER2 negative MBC, and how it will compare to the classic approach of using OFS plus an aromatase inhibitor.
Biospecimen retention
None retained
Biospecimen description
No exportation of biological samples.
Target sample size
160
Actual enrollment target size
160
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
15/03/2019
Date of study closure: Type
Anticipated
Date of study closure: Date
15/09/2021
Recruitment status
Not recruiting
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
Yes (Sharing Individual Participant Data) Presentation in a conference proceedings in mid-2019. Full publication in January 2020
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Sources of Monetary or Material Support
Name
Secondary Sponsors
Name
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Marwan
Ghosn
Center Sehnaoui, 894 Blvd Alfred Naccache, 5th Floor, Clinic Professor Marwan GHOSN, Achrafieh, Beirut
Lebanon
00961 1 613395 / 1 613396
marwanghosnmd@yahoo.com
Hotel Dieu de France Hospital
Scientific
Loay
El Kassem
Egypt
Egypt
00201003022907
loay.kassem@cairocure.com
AMCI
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hotel Dieu de France Hospital, Beirut
Marwan Ghosn
Hematology/Oncology
Approved
Hammoud Hospital University Medical Center, Saida
Fadi Farhat
Hematology/Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hotel Dieu de France
29/11/2018
Marwan Ghosn
drghosn@sodetel.net.lb
+9613226842
Hammoud Hospital University Medical Center
03/10/2018
Fadi Farhat
drfadi.trials@gmail.com
+9613753155
Countries of Recruitment
Name
Lebanon
Egypt
Algeria
South Africa
Health Conditions or Problems Studied
Condition
Code
Keyword
Breast Cancer
2-Propanol (T51.2)
Not applicable
Interventions
Intervention
Description
Keyword
MEDICINAL PRODUCT{S}: Palbociclib
MEDICINAL PRODUCT{S}: Palbociclib
Not applicable
Primary Outcomes
Name
Time points
Measure
Progression Free Survival (PFS)* as assessed by the Investigator.
Primary Endpoint: - Progression Free Survival (PFS)* as assessed by the Investigator. *PFS will be defined as the time from randomization to the time of disease progression or death for both treatment arms.
Primary Endpoint: - Progression Free Survival (PFS)* as assessed by the Investigator. *PFS will be defined as the time from randomization to the time of disease progression or death for both treatment arms.
Key Secondary Outcomes
Name
Time points
Measure
Objective Response (OR): Complete Response (CR) or Partial Response (PR).
Objective Response (OR): Complete Response (CR) or Partial Response (PR).
Objective Response (OR): Complete Response (CR) or Partial Response (PR).
Clinical benefit Rate (CBR): Complete Response + Partial Response + Stable Disease (SD) for 24 weeks
Clinical benefit Rate (CBR): Complete Response + Partial Response + Stable Disease (SD) for 24 weeks
Clinical benefit Rate (CBR): Complete Response + Partial Response + Stable Disease (SD) for 24 weeks
Overall Survival (OS)
Overall Survival (OS)
Overall Survival (OS)
Overall treatment safety: Type, incidence and severity of adverse events (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0)
Overall treatment safety: Type, incidence and severity of adverse events (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0)
Overall treatment safety: Type, incidence and severity of adverse events (as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.0)
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial