Metastatic Breast CancerPhase 2FATIMANCT02917005
PalbocIclib in PreMenopausal Women With ER Positive/HER-2 Negative MetAstatic Breast Cancer
A Phase 2 study testing Palbociclib, Exemestane and Goserelin in people with Metastatic Breast Cancer, run by Hamdy A. Azim at 1 site in South Africa.
Trial summary
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. Patients will be randomized to receive either palbociclib + exemestane + OFS (Arm 1) or exemestane +OFS (Arm 2). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Palbociclib, Exemestane and Goserelin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteSouth Africa
- Study dates
- 7 May 2019to Dec 2023
- 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
- 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.
- 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.
- HER2 negative breast cancer as confirmed by IHC, SISH or FISH.
- 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:
- 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].
- 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
Show all 13Show fewer
- 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.
- 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.
- ECOG Performance Status 0, 1, \& 2.
- 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).
- Adequate organ function as defined by the following criteria:
- Absolute neutrophil count (ANC) ≥ 1.5 10˄9/L ii. Platelets > 100 x10˄9/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).
- Written informed consent obtained before any trial related activity and according to local guidelines.
Who cannot join
- 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.
- Patients with primary endocrinal resistance, defined as recurrence within 24 months from the start of adjuvant tamoxifen treatment.
- Symptomatic and/or life threatening visceral metastases i. Diffuse lymphangitic carcinomatosis. ii. Bulky liver or pulmonary metastases
- Patients with only non-measurable lesions other than bone metastasis as defined above (e.g., pleural effusion, ascites, etc.).
- Patients who have received hormonal treatment other than neo/adjuvant tamoxifen
- ± LHRH agonist for their early breast cancer.
Show all 21Show fewer
- Patients who received prior chemotherapy for metastatic or recurrent breast cancer.
- 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.
- Uncontrolled (clinically or radiologically progressive) CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
- Major surgery within 3 weeks of first study treatment.
- 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.
- 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.
- Active bleeding diathesis.
- History of non-compliance to medical regimens. Patients unwilling to or unable to comply with the protocol.
- 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.
- Prior hematopoietic stem cell or bone marrow transplantation.
- 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.
- Known or possible hypersensitivity to goserelin during the adjuvant setting.
- Any severe and/or uncontrolled medical conditions such as:
- 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)
Trial locations and contacts
1 site in 1 country.
South Africa1 site, 1 recruiting
- Recruiting
Wits Oncology center
Johannesburg, 2050
Georgia Demetriou, M.D, georgiademetriou@hotmail.com
About this study
Official 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
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. Patients will be randomized to receive either palbociclib + exemestane + OFS (Arm 1) or exemestane +OFS (Arm 2).
Treatment will be continued until disease progression, unacceptable toxicities, or withdrawal of consent.
Read the detailed description
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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Palbociclib, Exemestane, Goserelin
- Keywords
- breast cancer, hormone receptor positive, HER2 negative, palbociclib, premenopausal
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalbociclibDrug
Also called Ibrance
CDK 4/6 inhibitor
ExemestaneDrug
Also called Aromasine
Aromatase inhibitor
GoserelinDrug
Also called Zoladex
LHRH agonist
| Study group | Role | What they receive |
|---|---|---|
| Palbociclib Arm | Experimental | Palbociclib (Pfizer) 125mg/day orally for 3 weeks followed by 1 week off plus Exemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days Receives: Drug: Palbociclib; Drug: Exemestane; Drug: Goserelin |
| Control Arm | Active comparator | Exemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days Receives: Drug: Exemestane; Drug: Goserelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Measured: 28 months
Secondary outcomes (4)
Overall response rate
Measured: 28 months
Clinical benefit rate
Measured: 28 months
Overall survival
Measured: 52 months
Incidence of treatment related adverse events
Measured: 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2016 (estimated)
- Study start7 May 2019
- Primary completionDec 2021 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hamdy A. Azim
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hamdy A. Azim, Africa Middle East Cancer Intergroup
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02917005
- Sponsor's protocol ID
- AMCI-001
- Acronym
- FATIMA
- Status last verified
- Jul 2021
- First submitted
- 18 Sep 2016
- Last updated
- 28 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Presentation in a conference proceedings in mid 2022 Full publication in January 2023
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02917005
- Acronym / sponsor ID
- FATIMA / AMCI-001
- Conditions
- Metastatic Breast Cancer
- Keywords
- breast cancer, hormone receptor positive, HER2 negative, palbociclib, premenopausal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Hamdy A. AzimUniversity, hospital or other
- Study start
- 7 May 2019 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 28 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. Patients will be randomized to receive either palbociclib + exemestane + OFS (Arm 1) or exemestane +OFS (Arm 2).
Treatment will be continued until disease progression, unacceptable toxicities, or withdrawal of consent.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Palbociclib Arm | Experimental | Drug: Palbociclib, Drug: Exemestane, Drug: GoserelinPalbociclib (Pfizer) 125mg/day orally for 3 weeks followed by 1 week off plus Exemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days |
| Control Arm | Active comparator | Drug: Exemestane, Drug: GoserelinExemestane (Pfizer) 25mg/day orally continuously plus Goserelin (Astrazeneca) 3.6 mg SC given every 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
- 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.
- HER2 negative breast cancer as confirmed by IHC, SISH or FISH.
- 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:
- 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
Key exclusion criteria (21 listed)
- 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.
- Patients with primary endocrinal resistance, defined as recurrence within 24 months from the start of adjuvant tamoxifen treatment.
- Symptomatic and/or life threatening visceral metastases i. Diffuse lymphangitic carcinomatosis. ii. Bulky liver or pulmonary metastases
- Patients with only non-measurable lesions other than bone metastasis as defined above (e.g., pleural effusion, ascites, etc.).
- Patients who have received hormonal treatment other than neo/adjuvant tamoxifen
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PalbociclibAlso: IbranceCDK 4/6 inhibitor | Drug | Palbociclib Arm |
| ExemestaneAlso: AromasineAromatase inhibitor | Drug | Control Arm, Palbociclib Arm |
| GoserelinAlso: ZoladexLHRH agonist | Drug | Control Arm, Palbociclib Arm |
Primary outcome
Progression free survival
Time frame: 28 months
4 secondary outcomes
Overall response rate
Time frame: 28 months
Clinical benefit rate
Time frame: 28 months
Overall survival
Time frame: 52 months
Incidence of treatment related adverse events
Time frame: 28 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2021.
- Individual participant dataSharing planned: Yes. Presentation in a conference proceedings in mid 2022 Full publication in January 2023
Related trials for Metastatic Breast Cancer
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
RecruitingPhase 1/2
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer
Metastatic Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Palbociclib, Exemestane and Goserelin in people with Metastatic Breast Cancer, run by Hamdy A. Azim at 1 site in South Africa.
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 13 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 28 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Loay M. Kassem, MD (01003022907, Loay.kassem@cairocure.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 28 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jul 2021.