Breast Cancer MetastaticPhase 2AMICANCT03555877
Anti-hormonal Therapie With Ribociclib in HR-positive / HER2- Negative Metastatic Breast Cancer
A Phase 2 study testing Ribociclib, Anastrozole and Letrozole in people with Breast Cancer Metastatic, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
This is a multicenter, prospective, randomized, open-label, controlled phase II study to test the addition of the CDK4/6 inhibitor ribociclib to anti-hormonal treatment as maintenance therapy in patients with disease control (at least stable disease) after 1st line chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Metastatic
- What is being tested?
- Ribociclib, Anastrozole and Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteGermany
- Study dates
- 15 Mar 2018to 21 Jul 2022
- 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
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- Female patients.
- Age ≥ 18 years old.
- Histologically confirmed HER2-/HR+ locally advanced or metastatic invasive breast carcinoma assessed on the primary tumor and/or on the metastatic lesions (preferred).
- Willingness and ability to provide archived formalin fixed paraffin embedded tissue block or a partial block from primary surgery and/or tumor or metastasis biopsy, which will be used for further breast cancer research.
- Maintenance endocrine therapy could have already been started up to 6 weeks before randomization, but after achievement of tumor response or stable disease.
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- Maintenance therapy must be preceded prior to randomization by at least 4 cycles of a mono- or polychemotherapy. Tumor response or stable disease needs to be maintained to allow entry into the trial. Study treatment must start within 8 weeks of the last dose of chemotherapy.
- Previous therapy with maximum one line of anti-hormonal treatment is allowed.
- Previous neoadjuvant/adjuvant therapy is allowed. In case of cancer other than breast cancer, treatment should be completed more than 5 years before study entry.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.03 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
- The patient must be accessible for scheduled visits, treatment and follow-up. Patients registered on this trial must be treated at the participating center which could be the Principal or a Co- investigator's site.
- Life-expectancy > 6 months.
- The subjects need to be either A) of non-childbearing potential (documented postmenopausal or post hysterectomy) or B) childbearing potential with negative urinary pregnancy test (in this case patients need to use highly effective non-hormonal contraceptive).
Who cannot join
- Uncontrolled/untreated central nervous system lesions.
- Known severe hypersensitivity reactions to compounds similar to one of the investigational (active substance or peanut, soya or other excipients) and supportive treatment.
- Inadequate organ function immediate prior to randomization including:
- Hemoglobin < 10 g/dL
- Absolute neutrophil count (ANC) < 2000/mm³ (< 2.0 x 109/L)
- Platelets < 100,000/mm³ (< 100 x 109/L)
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- Alanine aminotransferase (ALAT/SGPT) and/or aspartate aminotransferase (ASAT/SGOT) > 2.0 x upper normal limits (ULN). If the patient has liver metastases, ALT and AST should not be ≥5 ULN.
- Alkaline phosphatase (ALP) > 2.5 x ULN
- Total serum bilirubin > 1.5 x ULN
- Serum creatinine >1.5 x ULN or estimated creatinine clearance < 60 mL/min as calculated using the method standard for the Institution
- Severe and relevant comorbidity that would interact with the participation in the study.
- Previous malignant disease being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
- Evidence for active infection including wound infections and anamnestic HIV or hepatitis.
- QTc >450 msec or a family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.
- Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (i.e. hypocalcemia, hypokalemia, hypomagnesemia).
- Any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE version 4.03 grade ≥ 2, atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism.
- Other severe acute, uncontrolled or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
- Patients treated within the last 7 days prior to randomization with drugs known to be CYP3A4 inhibitors or inducers (see section 11.4) or drugs that are known to prolong the QT interval.
- Pregnant and lactating women.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Anti-hormonal Maintenance Treatment With the CDK4/6 Inhibitor Ribociclib After 1st Line Chemotherapy in Hormone Receptor Positive / HER2 Negative Metastatic Breast Cancer: A Phase II Trial
This is a multicenter, prospective, randomized, open-label, controlled phase II study to test the addition of the CDK4/6 inhibitor ribociclib to anti-hormonal treatment as maintenance therapy in patients with disease control (at least stable disease) after 1st line chemotherapy.
Read the detailed description
Although 1st line chemotherapy is effective in women with HR-positive HER2-negative breast cancer, PFS is usually around 6-8 months and 2nd or 3rd line treatments are by far less effective. Well tolerated maintenance treatments with the potential to prolong PFS and even OS are urgently needed. This study evaluates the impact of the addition of a CDK4/6 inhibitor to an anti-hormonal maintenance treatment of physicians´ choice.
- Conditions
- Breast Cancer Metastatic
- Being tested
- Ribociclib, Anastrozole, Letrozole, Exemestane, Fulvestrant
- Keywords
- Ribociclib, Anti-hormonal maintainance treatment, HR-positive, HER2-negative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibociclibDrug
Also called Kisqali
Ribociclib in addition to endocrine maintenance therapy. Endocrine therapy, at the discretion of the investigator, could have already been started up to 4 weeks before randomization but not later than with first dose of ribociclib.
AnastrozoleDrug
Also called All marketed medicinal products with this active ingredient.
1mg once daily as indicated in the SmPC
LetrozoleDrug
Also called All marketed medicinal products with this active ingredient.
2,5mg once daily as indicated in the SmPC
ExemestaneDrug
Also called All marketed medicinal products with this active ingredient.
25mg once daily as indicated in the SmPC
FulvestrantDrug
Also called All marketed medicinal products with this active ingredient.
(prefilled syringes with fulvestrant 250mg each), 500mg given once a month, with an additional 500mg dose given two weeks after the first dose as indicated in the SmPC
| Study group | Role | What they receive |
|---|---|---|
| Anti-hormonal treatment + ribociclib | Experimental | In the experimental arm ribociclib will be dosed on a flat scale of 600mg/day (corresponding to three 200mg tablets once daily, 3 week on, one week off). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant. Receives: Drug: Ribociclib; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Fulvestrant |
| Anti-hormonal treatment | Active comparator | In the control arm patients will receive endocrine treatment only (of choise of investigator). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant. Receives: Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Locally-assessed progression-free survival (PFS)
Primary efficacy endpoint is locally-assessed progression-free survival (PFS) defined as the time elapsed between randomization and tumor progression or death from any cause.
Measured: Up to 39 months
Secondary outcomes (5)
The impact on overall survival
Overall survival (OS) defined as the time elapsed between treatment randomization and death from any cause
Measured: Up to 39 months
The clinical benefit rate
Clinical benefit rate (CBR) defined as the proportion of subjects with best response of complete response, partial response, or stable disease for at least 24 weeks
Measured: Up to 39 months
Patient reported outcomes
will be assessed using the General Quality of Life questionnaire (FACT-B), which will be filled in at study entry and every three month thereafter.
Measured: Up to 39 months
Number of participants with adverse events, serious adverse events and adverse events of special interest as assessed by CTCAE v4.03.
Number of participants with adverse events, serious adverse events and adverse events of special interest as assessed by CTCAE v4.03 compared between the two treatment-arms.
Measured: Up to 33 months
The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that.
The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that compared between two treatment-arms.
Measured: Up to 33 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2018
- Study start15 Mar 2018
- Primary completion21 Jul 2022
- Study completion21 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer MetastaticStudies 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
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thomas Decker, Prof. Dr., Principal investigator, Gemeinschaftspraxis Onkologie Ravensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03555877
- Sponsor's protocol ID
- GBG 97
- Acronym
- AMICA
- Status last verified
- Jul 2023
- First submitted
- 16 Feb 2018
- Last updated
- 7 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1351-60. doi: 10.1016/S1470-2045(14)70444-9. Epub 2014 Sep 28.
PubMed 25273343Decker T, Ludtke-Heckenkamp K, Melnichuk L, Hirmas N, Lubbe K, Zahn MO, Schmidt M, Denkert C, Lorenz R, Muller V, Zahm DM, Mundhenke C, Bauer S, Thill M, Seropian P, Filmann N, Loibl S. Anti-hormonal maintenance treatment with the CDK4/6 inhibitor ribociclib after 1st line chemotherapy in hormone receptor positive / HER2 negative metastatic breast cancer: A phase II trial (AMICA). Breast. 2023 Dec;72:103575. doi: 10.1016/j.breast.2023.08.007. Epub 2023 Sep 1.
PubMed 37690320
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-hormonal Maintenance Treatment With the CDK4/6 Inhibitor Ribociclib After 1st Line Chemotherapy in Hormone Receptor Positive / HER2 Negative Metastatic Breast Cancer: A Phase II Trial
- ClinicalTrials.gov ID
- NCT03555877
- Acronym / sponsor ID
- AMICA / GBG 97
- Conditions
- Breast Cancer Metastatic
- Keywords
- Ribociclib, Anti-hormonal maintainance treatment, HR-positive, HER2-negative
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Study start
- 15 Mar 2018 (actual)
- Primary completion
- 21 Jul 2022 (actual)
- Study completion
- 21 Jul 2022 (actual)
- First posted
- 14 Jun 2018 (actual)
- 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 a multicenter, prospective, randomized, open-label, controlled phase II study to test the addition of the CDK4/6 inhibitor ribociclib to anti-hormonal treatment as maintenance therapy in patients with disease control (at least stable disease) after 1st line chemotherapy.
Detailed description
Although 1st line chemotherapy is effective in women with HR-positive HER2-negative breast cancer, PFS is usually around 6-8 months and 2nd or 3rd line treatments are by far less effective. Well tolerated maintenance treatments with the potential to prolong PFS and even OS are urgently needed. This study evaluates the impact of the addition of a CDK4/6 inhibitor to an anti-hormonal maintenance treatment of physicians´ choice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anti-hormonal treatment + ribociclib | Experimental | Drug: Ribociclib, Drug: Anastrozole, Drug: Letrozole, Drug: Exemestane, Drug: FulvestrantIn the experimental arm ribociclib will be dosed on a flat scale of 600mg/day (corresponding to three 200mg tablets once daily, 3 week on, one week off). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant. |
| Anti-hormonal treatment | Active comparator | Drug: Anastrozole, Drug: Letrozole, Drug: Exemestane, Drug: FulvestrantIn the control arm patients will receive endocrine treatment only (of choise of investigator). Anti-hormonal/endocrine treatment of choice of investigator: anastrozole, exemestane, letrozole, fulvestrant. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- Female patients.
- Age ≥ 18 years old.
- Histologically confirmed HER2-/HR+ locally advanced or metastatic invasive breast carcinoma assessed on the primary tumor and/or on the metastatic lesions (preferred).
- Willingness and ability to provide archived formalin fixed paraffin embedded tissue block or a partial block from primary surgery and/or tumor or metastasis biopsy, which will be used for further breast cancer research.
Key exclusion criteria (20 listed)
- Uncontrolled/untreated central nervous system lesions.
- Known severe hypersensitivity reactions to compounds similar to one of the investigational (active substance or peanut, soya or other excipients) and supportive treatment.
- Inadequate organ function immediate prior to randomization including:
- Severe and relevant comorbidity that would interact with the participation in the study.
- Previous malignant disease being disease-free for less than 5 years (except CIS of the cervix and non-melanomatous skin cancer).
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 |
|---|---|---|
| RibociclibAlso: KisqaliRibociclib in addition to endocrine maintenance therapy. Endocrine therapy, at the discretion of the investigator, could have already been started up to 4 weeks before randomization but not later than with first dose of ribociclib. | Drug | Anti-hormonal treatment + ribociclib |
| AnastrozoleAlso: All marketed medicinal products with this active ingredient.1mg once daily as indicated in the SmPC | Drug | Anti-hormonal treatment, Anti-hormonal treatment + ribociclib |
| LetrozoleAlso: All marketed medicinal products with this active ingredient.2,5mg once daily as indicated in the SmPC | Drug | Anti-hormonal treatment, Anti-hormonal treatment + ribociclib |
| ExemestaneAlso: All marketed medicinal products with this active ingredient.25mg once daily as indicated in the SmPC | Drug | Anti-hormonal treatment, Anti-hormonal treatment + ribociclib |
| FulvestrantAlso: All marketed medicinal products with this active ingredient.(prefilled syringes with fulvestrant 250mg each), 500mg given once a month, with an additional 500mg dose given two weeks after the first dose as indicated in the SmPC | Drug | Anti-hormonal treatment, Anti-hormonal treatment + ribociclib |
Primary outcome
Locally-assessed progression-free survival (PFS)
Time frame: Up to 39 months
Primary efficacy endpoint is locally-assessed progression-free survival (PFS) defined as the time elapsed between randomization and tumor progression or death from any cause.
5 secondary outcomes
The impact on overall survival
Time frame: Up to 39 months
The clinical benefit rate
Time frame: Up to 39 months
Patient reported outcomes
Time frame: Up to 39 months
Number of participants with adverse events, serious adverse events and adverse events of special interest as assessed by CTCAE v4.03.
Time frame: Up to 33 months
The number of patients who reduced, interrupted or permanently discontinued treatment and the reasons for that.
Time frame: Up to 33 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
- Background: PubMed 25273343Gligorov J, Doval D, Bines J, Alba E, Cortes P, Pierga JY, Gupta V, Costa R, Srock S, de Ducla S, Freudensprung U, Mustacchi G. Maintenance capecitabine and bevacizumab versus bevacizumab alone after initial first-line bevacizumab and docetaxel for patients with HER2-negative metastatic breast cancer (IMELDA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1351-60. doi: 10.1016/S1470-2045(14)70444-9. Epub 2014 Sep 28.
- Derived from this study: PubMed 37690320Decker T, Ludtke-Heckenkamp K, Melnichuk L, Hirmas N, Lubbe K, Zahn MO, Schmidt M, Denkert C, Lorenz R, Muller V, Zahm DM, Mundhenke C, Bauer S, Thill M, Seropian P, Filmann N, Loibl S. Anti-hormonal maintenance treatment with the CDK4/6 inhibitor ribociclib after 1st line chemotherapy in hormone receptor positive / HER2 negative metastatic breast cancer: A phase II trial (AMICA). Breast. 2023 Dec;72:103575. doi: 10.1016/j.breast.2023.08.007. Epub 2023 Sep 1.
- GBG website active studiesLink provided by the sponsor.
- 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.
Thomas Decker, Prof. Dr. principal investigator
Gemeinschaftspraxis Onkologie Ravensburg
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 Ribociclib, Anastrozole and Letrozole in people with Breast Cancer Metastatic, run by GBG Forschungs GmbH at 1 site in Germany.
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 14 inclusion and 20 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: finished, as of the sponsor's last update on 7 Jul 2023. 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 Germany. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Locally-assessed progression-free survival (PFS) (time frame: Up to 39 months). 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 NCT03555877, which also lists 2 linked publications.
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 7 Jul 2023.