Metastatic Breast CancerPhase 3FUMANCENCT02383030
Fulvestrant as Maintenance Therapy After First-line Chemotherapy in HER2 - Postmenopausal MBC Patients
A Phase 3 study testing Fulvestrant in people with Metastatic Breast Cancer, run by Consorzio Oncotech at 20 sites in Italy.
Trial summary
Breast cancer is one of the most prevalent cancers among women, and represents 20 - 25% of all female cancers. Despite earlier diagnosis and improvement in adjuvant therapies, some patients will present metastatic recurrence. Treatment of breast cancer is determined by the extent of the disease. 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?
- Fulvestrant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 20 sitesItaly
- Study dates
- Nov 2015to Dec 2017
- Phase
- Phase 3
- 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 or cytologically diagnosis of breast cancer;
- Presence of metastatic disease either measureable or non-measureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors;
- Diagnosis of hormone receptor positive (HR+), HER2 negative breast cancer. To fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (estrogen receptor [ER], progesterone receptor [PR]). To fulfill the requirement for HER2 negative disease, a breast cancer must not demonstrate over-expression of HER2 by either IHC or fluorescence in-situ hybridization (FISH);
- Post-menopausal status at the time of randomization.
- Previous treatment with either an antiestrogen or an aromatase inhibitor for adjuvant or metastatic disease is allowed;
- Age >18;
Show all 17Show fewer
- One line chemotherapy for metastatic disease discontinued for 21-28 days. Patient has to have response or stability from the first-line chemotherapy. The patient may have received prior systemic chemotherapy in the neo-adjuvant or adjuvant setting;
- Patients with measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria;
- Performance Status (ECOG) <2;
- No brain metastases;
- No clinically serious concurrent illnesses;
- Adequate organ function
- Use of bisphosphonates are allowed;
- Use of antiangiogenetic drugs (bevacizumab associated to paclitaxel) is allowed, but discontinued 21-28 days before start study;
- Life expectancy > 12 weeks;
- Are willing to participate for the duration of the study and to follow study procedures;
- Written informed consent prior to any study-specific procedures Written informed consent;
Who cannot join
- Treatment with a drug that has not received regulatory approval for any indication within 21-28 days from the randomization;
- Drug (chemotherapy or biological drug) after the end of first-line chemotherapy for maintenance phase;
- Significant known cardiovascular impairment (NYHA CHF > grade 2, unstable angina, myocardial infarction within the previous 6 months prior to randomization, or existing serious cardiac arrhythmia). VECF (Ventricular Ejection Cardiac Fraction) ≤ 50%;
- Prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to randomization;
- Severe/uncontrolled intercurrent illness within the previous 28 days prior to randomization.
- Any other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation;
- Patients with psychiatric illness, social situation or geographical situation that would preclude informed consent or limit compliance with study requirements, as determined by the Investigator;
Trial locations and contacts
20 sites in 1 country.
Elena Abrami, BD contact
20 sites in 1 country
Italy20 sites, 20 recruiting
- Not yet recruiting
Ospedale C. e G. Mazzoni di Ascoli Piceno - Area Vasta 5
Ascoli Piceno
Giorgio De Signoribus
- Not yet recruiting
P.O. Avezzano Via G. di Vittorio, 6
Avezzano
Giovanna Amiconi
- Not yet recruiting
A.S.U.R. Zona Territoriale 6 Fabriano U.O. Oncologia Medica
Fabriano, Ancona, 60044
ROSA RITA SILVA, Md
- Recruiting
Ospedale degli Infermi - Faenza
Faenza
Laura Amaducci
- Not yet recruiting
A.O.U Ospedali Riuniti di Foggia
Foggia
Sante Romito
- Not yet recruiting
A.S.L. LT - Ospedale Santa Maria Goretti U.O.C. di Oncologia Medica
Latina, Latina, 04100
ENZO VELTRI, Md
- Recruiting
Ospedale Vito Fazzi
Lecce, 73100
Mariangela Ciccarese, MD
Mariangela Ciccarese, MD
- Recruiting
Ospedale Unico Versilia U.O. Oncologia Medica
Lido di Camaiore, Lucca, 55041
Domenico Amoroso, Md
- Recruiting
P.O. Campo di Marte
Lucca
Editta Baldini
- Not yet recruiting
Presidio Ospedaliero di Macerata
Mecerata, MC, 62100
Luciano LL Latini, Doctor
- Not yet recruiting
Azienda Ospedaliera Fatebenefratelli e Oftalmico
Milan
Nicla La Verde
- Recruiting
Istituto Nazionale dei Tumori - Fondazione G. Pascale U.O. Oncologia Medica Senologica
Naples, Napoli, 80131
MICHELINO DE LAURENTIIS, Md
- Recruiting
A.O.R.N. "A. Cardarelli"
Naples
Ferdinando Riccardi
- Recruiting
Università di Napoli Federico II Dipartimento di Medicina clinica e Chirurgia
Naples
Sabino De Placido
- Recruiting
Ospedale 'Felice Lotti' - Azienda USL 5 di Pisa U.O. di Oncologia Medica
Pontedera, Pisa, 56025
Giacomo Allegrini, MD
- Recruiting
Ospedale di Ravenna
Ravenna
Amelia Tienghi
- Recruiting
Ospedale Oncologico Regionale - Centro di Riferimento Oncologico di Basilicata U.O. di Oncologia Medica
Rionero in Vulture, Potenza, 85028
Michele Aieta, MD
- Recruiting
Istituto Regina Elena per lo studio e la cura dei tumori S.C. Oncologia Medica A
Roma, Roma, 00144
Alessandra Fabi, mD
- Not yet recruiting
Ospedale fatebenefratelli - Villa S Pietro (Roma)
Roma
Arianna Pellegrino
- Not yet recruiting
Ospedale civile "Madonna del Soccorso" - Area Vasta 5
San Benedetto del Tronto
Giorgio De signoribus
About this study
Official title: Randomized Phase III Study of Fulvestrant as Maintenance Therapy After First-line Chemotherapy in HER2 Negative Postmenopausal Metastatic Breast Cancer Patients
Breast cancer is one of the most prevalent cancers among women, and represents 20 - 25% of all female cancers. Despite earlier diagnosis and improvement in adjuvant therapies, some patients will present metastatic recurrence.
Treatment of breast cancer is determined by the extent of the disease. Early or localized breast cancer is treated by a combination of surgery and radiotherapy. Adjuvant systemic therapy, consisting of chemotherapy and/or endocrine therapy, in tumors deemed hormone responsive, can prolong the disease-free interval and improve overall survival. However, approximately 30% to 40% of patients with early breast cancer will ultimately relapse, with either local recurrence or distant metastases, and require further systemic treatment for advanced disease.
Read more
Since breast cancer that recurs or progresses after initial treatment is considered incurable, the therapy options available for advanced disease are concerned with disease control and palliation of symptoms.
Hormonal therapy has become the treatment of choice in postmenopausal women with hormone sensitive breast cancer. Even though the treatment of advanced breast cancer in postmenopausal women has improved with the introduction of agents such as aromatase inhibitors, these agents still have limitations, and disease management continues to be sub-optimal. The use of systemic therapies such as hormonal therapy, chemotherapy or new biological treatment is to reduce tumour masses, improve survival and preserve quality of life. Whatever the initial efficacy of the treatment undertaken in metastatic setting, almost every patient will relapse. The main goal is to improve progression free survival (PFS). To achieve this, the type of chemotherapy, the optimal duration of chemotherapy, the benefit of maintenance chemotherapy, the benefit of maintenance hormonal treatment are debatable.
Read the detailed description
The search for prognostic and predictive factors that could influence the survival of patients treated for metastatic breast cancer has already been the subject of several studies. It seems that 2 components in the natural outcome of tumors must be considered. The first category is related to the primary characteristics such as initial histological grade, hormonal receptor status. The second category is linked to the metastatic characteristics: proliferation index reflected by the length of disease-free interval, type and number of metastatic sites involved. On the other hand, some prognostic factors are linked to the treatments undertaken, stressing their impact on the natural outcome of the disease: type of hormonotherapy, type of chemotherapy, type of response achieved by treatment.
The impact of some factors remains debatable, such the duration of treatment. The optimal duration of chemotherapy in patients who respond or have stable disease is not identified.
Definitively, the major limit to the use of prolonged regimens of chemotherapy is related to their toxicity, all the more so as they are cumulative (cardiac toxicity of anthracyclins, neurologic toxicity of taxanes, haematological cumulative toxicities with any chemotherapy…). The proposition to give hormonal treatment to prolong therapy in hormonal-positive tumors is another possible option. In the literature, data focused on this strategy are rare.
One can object that the choice of patient/tumor characteristics for who would or would not receive the maintenance hormonal therapy was not random, or controlled in any way. This may have led to a selection of better prognosis patients. Investigators cannot know whether they are observing natural history or impacting it in such a trial. Nevertheless the major impact obtained by maintenance hormonal treatment after the first line chemotherapy might indicate that this strategy should be recommended in patients with an ER or PgR positive tumor. Based on the amplitude of the benefit observed, it may be ethically debatable to conduct a prospective randomized study. Moreover, randomized trials which assess the benefit of a new chemotherapy regimen should allow the possibility to give maintenance hormonal treatment.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Fulvestrant
- Keywords
- Breast cancer, Metastatic, HER2 negative, postmenopausal, maintenance therapy, fulvestrant
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FulvestrantDrug
Also called Faslodex
After randomization patients will receive (Arm A, experimental Arm) fulvestrant as the following schedule: 500 mg i.m. on Days 0, 14, 28 followed by fulvestrant 500 mg im given every 28 days until progression disease. Study will start after 42 days from the last cycle of chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Fulvestrant | Experimental | In Arm A maintenance Fulvestrant will be given until disease progression, unacceptable toxicity or refused of patient to the treatment. Receives: Drug: Fulvestrant |
| No intervention | No intervention | Patients will be randomized to receive fulvestrant (experimental arm) or no treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maintenance-progression-free survival (mPFS)
Time between the date of randomization and the date of progression or death, whichever occurs first
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2015 (estimated)
- Study startNov 2015
- Primary completionSep 2017 (estimated)
- Study completionDec 2017 (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 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Consorzio Oncotech
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Research Technology S.r.l.
- Responsible party
- Sponsor
- Investigators
- Francesco Cognetti, Study chair, Regina Elena National Cancer Institute Via Elio Chianesi 53, 00144 Rome, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02383030
- Sponsor's protocol ID
- GIM18-FUMANCE
- Other IDs
- 2014-003798-41, 2014
- Acronym
- FUMANCE
- Status last verified
- Jun 2016
- First submitted
- 26 Feb 2015
- Last updated
- 15 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase III Study of Fulvestrant as Maintenance Therapy After First-line Chemotherapy in HER2 Negative Postmenopausal Metastatic Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT02383030
- Acronym / sponsor ID
- FUMANCE / GIM18-FUMANCE
- Conditions
- Metastatic Breast Cancer
- Keywords
- Breast cancer, Metastatic, HER2 negative, postmenopausal, maintenance therapy, fulvestrant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 156 participants (estimated)
- Lead sponsor
- Consorzio OncotechUniversity, hospital or other
- Collaborators
- Clinical Research Technology S.r.l.
- Study start
- Nov 2015
- Primary completion
- Sep 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 9 Mar 2015 (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.
Breast cancer is one of the most prevalent cancers among women, and represents 20 - 25% of all female cancers. Despite earlier diagnosis and improvement in adjuvant therapies, some patients will present metastatic recurrence.
Treatment of breast cancer is determined by the extent of the disease. Early or localized breast cancer is treated by a combination of surgery and radiotherapy. Adjuvant systemic therapy, consisting of chemotherapy and/or endocrine therapy, in tumors deemed hormone responsive, can prolong the disease-free interval and improve overall survival. However, approximately 30% to 40% of patients with early breast cancer will ultimately relapse, with either local recurrence or distant metastases, and require further systemic treatment for advanced disease.
Since breast cancer that recurs or progresses after initial treatment is considered incurable, the therapy options available for advanced disease are concerned with disease control and palliation of symptoms.
Hormonal therapy has become the treatment of choice in postmenopausal women with hormone sensitive breast cancer. Even though the treatment of advanced breast cancer in postmenopausal women has improved with the introduction of agents such as aromatase inhibitors, these agents still have limitations, and disease management continues to be sub-optimal. The use of systemic therapies such as hormonal therapy, chemotherapy or new biological treatment is to reduce tumour masses, improve survival and preserve quality of life. Whatever the initial efficacy of the treatment undertaken in metastatic setting, almost every patient will relapse. The main goal is to improve progression free survival (PFS). To achieve this, the type of chemotherapy, the optimal duration of chemotherapy, the benefit of maintenance chemotherapy, the benefit of maintenance hormonal treatment are debatable.
Detailed description
The search for prognostic and predictive factors that could influence the survival of patients treated for metastatic breast cancer has already been the subject of several studies. It seems that 2 components in the natural outcome of tumors must be considered. The first category is related to the primary characteristics such as initial histological grade, hormonal receptor status. The second category is linked to the metastatic characteristics: proliferation index reflected by the length of disease-free interval, type and number of metastatic sites involved. On the other hand, some prognostic factors are linked to the treatments undertaken, stressing their impact on the natural outcome of the disease: type of hormonotherapy, type of chemotherapy, type of response achieved by treatment.
The impact of some factors remains debatable, such the duration of treatment. The optimal duration of chemotherapy in patients who respond or have stable disease is not identified.
Definitively, the major limit to the use of prolonged regimens of chemotherapy is related to their toxicity, all the more so as they are cumulative (cardiac toxicity of anthracyclins, neurologic toxicity of taxanes, haematological cumulative toxicities with any chemotherapy…). The proposition to give hormonal treatment to prolong therapy in hormonal-positive tumors is another possible option. In the literature, data focused on this strategy are rare.
One can object that the choice of patient/tumor characteristics for who would or would not receive the maintenance hormonal therapy was not random, or controlled in any way. This may have led to a selection of better prognosis patients. Investigators cannot know whether they are observing natural history or impacting it in such a trial. Nevertheless the major impact obtained by maintenance hormonal treatment after the first line chemotherapy might indicate that this strategy should be recommended in patients with an ER or PgR positive tumor. Based on the amplitude of the benefit observed, it may be ethically debatable to conduct a prospective randomized study. Moreover, randomized trials which assess the benefit of a new chemotherapy regimen should allow the possibility to give maintenance hormonal treatment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fulvestrant | Experimental | Drug: FulvestrantIn Arm A maintenance Fulvestrant will be given until disease progression, unacceptable toxicity or refused of patient to the treatment. |
| No intervention | No intervention | –Patients will be randomized to receive fulvestrant (experimental arm) or no treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically or cytologically diagnosis of breast cancer;
- Presence of metastatic disease either measureable or non-measureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors;
- Diagnosis of hormone receptor positive (HR+), HER2 negative breast cancer. To fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of the hormone receptors (estrogen receptor [ER], progesterone receptor [PR]). To fulfill the requirement for HER2 negative disease, a breast cancer must not demonstrate over-expression of HER2 by either IHC or fluorescence in-situ hybridization (FISH);
- Post-menopausal status at the time of randomization.
- Previous treatment with either an antiestrogen or an aromatase inhibitor for adjuvant or metastatic disease is allowed;
Key exclusion criteria (7 listed)
- Treatment with a drug that has not received regulatory approval for any indication within 21-28 days from the randomization;
- Drug (chemotherapy or biological drug) after the end of first-line chemotherapy for maintenance phase;
- Significant known cardiovascular impairment (NYHA CHF > grade 2, unstable angina, myocardial infarction within the previous 6 months prior to randomization, or existing serious cardiac arrhythmia). VECF (Ventricular Ejection Cardiac Fraction) ≤ 50%;
- Prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to randomization;
- Severe/uncontrolled intercurrent illness within the previous 28 days prior to randomization.
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 |
|---|---|---|
| FulvestrantAlso: FaslodexAfter randomization patients will receive (Arm A, experimental Arm) fulvestrant as the following schedule: 500 mg i.m. on Days 0, 14, 28 followed by fulvestrant 500 mg im given every 28 days until progression disease. Study will start after 42 days from the last cycle of chemotherapy | Drug | Fulvestrant |
Primary outcome
Maintenance-progression-free survival (mPFS)
Time frame: 36 months
Time between the date of randomization and the date of progression or death, whichever occurs first
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2016.
- Individual participant dataSharing planned: No
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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.
Elena Abrami, BD contact
Francesco Cognetti study chair
Regina Elena National Cancer Institute Via Elio Chianesi 53, 00144 Rome, Italy
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fulvestrant in people with Metastatic Breast Cancer, run by Consorzio Oncotech at 20 sites in Italy.
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 17 inclusion and 7 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 15 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Alessandra Fabi, MD (652666919, fabi@ifo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maintenance-progression-free survival (mPFS) (time frame: 36 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 15 Jun 2016.