Breast CancerPhase 1/2NCT03344536
A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer
A Phase 1/2 study testing Fulvestrant and Debio 1347 in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of a phase Ib study is to find out the best or maximum tolerated dose of a medication or combination of medications. Therefore, the purpose of this study is to decide the best dose of the study drug, Debio 1347, that can be given in combination with the standard hormonal drug, fulvestrant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Fulvestrant and Debio 1347
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Nov 2017to 12 Aug 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and Females Age > 18 years
- Written informed consent and authorization obtained from the subject/HIPAAappointed legal representative prior to performing any protocol-related procedures including screening evaluations
- Patients with metastatic histologically or cytologically confirmed invasive breast cancer
- Female patients of postmenopausal status. with metastatic histologically or cytologically confirmed invasive breast cancer.
- Postmenopausal status will be defined as following:
- Age ≥ 60 years
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- Age < 60 years and 12 months of amenorrhea plus follicle stimulating hormone and plasma estradiol levels within postmenopausal range by local laboratory assessment in the absence of oral contraceptive pills, hormone replacement therapy, or gonadotropin-releasing hormone (GnRH) agonist or antagonist
- Prior bilateral oophorectomy
- Pre or perimenopausal women allowed with the addition of goserelin
- ECOG performance status 0 -1
- Tumor must be estrogen receptor and/or progesterone receptor positive ( i.e. Hormone receptor positive (HR+) and HER-2 negative as defined by the ASCO-CAP guidelines: HR+ is defined as expression of ER and/PR in ≥ 1% of cells, or HR+ by local laboratory or regional definition. HER2- is defined as a HER2 IHC score of 0 or 1+ , or an IHC score of 2+ accompanied by a negative fluorescence, chromogenic, or silver in situ hybridization test indicating the absence of HER2 gene amplification, or a HER2/CEP17 ratio of < 2.0, or local clinical guidelines.
- Tumors must have FGFR amplifications as determined by a CLIA certified laboratory. Patients with FGFR amplifications co-occurring with 11q amplification (CCND1, FGF3,4, 19 amplifications) are also eligible.
- Measurable or evaluable disease per RECIST1.1 or pure lytic or mixed lytic-blastic bone lesions
- No more than 1 prior chemotherapy regimen in the metastatic setting for the phase 2 portion. Patients in the phase 1 portion could have received any number of prior lines of therapy.
- Willing to undergo a new core or excisional biopsy from a metastatic, not previously irradiated tumor lesion during screening
- Life expectancy of greater than 3 months
- Archival Tumor (up to 10 unstained slides) will be obtained, whenever available for additional biomarker analyses
- Hematologic parameters:
- White blood cell (WBC) count of > 3000/ul
- Absolute neutrophil count (ANC) > 1000/ul
- Platelets > 100,000/ul, hemoglobin > 9.0 g/dl
- Non-hematologic parameters:
- Corrected calcium value </= 1.1 x ULN
- Total bilirubin ≤1.5 x ULN (upper limit of normal) except subject with documented Gilbert"s syndrome (≤5 x ULN) or liver metastasis, who must have a baseline total bilirubin ≤3.0 mg/dL
- AST and ALT ≤ 3 x ULN, unless associated with hepatobiliary metastases, in that case ≤5 x ULN
- ALP </= 2.5 x ULN or </= 5.0 x ULN for patients with bone metastases
- Gamma-glutamyltransferase </= 2.5 x ULN
- Albumin >/= 2.5 g/dL
- Phosphat </= 1.1 x ULN
- Prothrombin time (PT) and/or prothrombin time international normalized ratio (PT-INR) and/or activated partial thromboplastin time (APTT) </= 1.3 x ULN
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min on the basis of the
- Cockcroft-Gault glomerular filtration rate estimation:
- (140 - age) × (weight in kg) × (0.85 if female, 1.0 if male) 72 × (serum creatinine in mg/dL)
- Patients with "treated and stable" brain lesions for a duration of > 4 weeks may be enrolled.
- Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication and agree to use effective contraception. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Who cannot join
- Prior Fulvestrant for metastatic breast cancer will be allowed for phase 1 portion but not for the phase 2 portion
- History of hypersensitivity to any of the excipients in the Debio 1347 formulation (lactose hydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, sodium lauryl sulfate, and magnesium stearate).
- Other malignancies requiring active treatment in the last 6 months.
- Brain tumors and/or brain metastases unless they are asymptomatic, stable on recent imaging (not dated more than 30 days from the inclusion date), and have not required active treatment in the last 6 months.
- History and/or current evidence of endocrine alteration of calcium-phosphate homeostasis.
- History of myocardial infarction or stroke within 6 months, congestive heart failure greater than NYHA class II, unstable angina pectoris, unexplained recurrent syncope, cardiac arrhythmia requiring treatment or family history of sudden death from cardiacrelated causes.
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- Baseline Frederica"s corrected QT (QTcF) interval greater than 470 msec (female) or greater than 450 msec (male), history of congenital long QT syndrome, the presence in the screening ECG of a conduction abnormality that in the opinion of the Investigator would preclude safe participation in this study.
- Concomitant use of a drug with a known risk of QTc prolongation
- Current anticoagulation therapy with therapeutic doses of warfarin (low-dose warfarin ≤ 1mg/day or low molecular-weight heparin are permitted).
- History and or current evidence of ectopic mineralisation/calcification including but not limited to the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic coronary calcification.
- Concomitant use of high dose systemic steroids and other drugs such as calcitonin preparations, active Vitamin D3 preparations, estrogen preparations, selective estrogen receptor modulators, Vitamin K2 preparations, parathyroid hormones, phosphorus absorbers. Note, inhaled, topical steroids and low tapering doses of steroid especially in patients treated recently for brain metastases will be included.
- Corneal disease, such as bullous or band keratopathy, corneal desquamation, keratitis, corneal ulcer, or keratoconjunctivitis.
- Known infection requiring the systemic use of, for example, an antibiotic or antiviral agent.
- Known HIV, HBV or HCV infection.
- Known untreated or uncontrolled acute infection, including urinary tract infection, within 7 days of study entry.
- History of organ, bone marrow, or stem cell transplantation.
- Pregnant or lactating woman (any woman of childbearing potential who has menstruated within the year prior to enrolment will undergo pregnancy testing within 72 hours prior to receiving the first dose of study medication).
- Women of childbearing potential or men who are unwilling to use an appropriate method of contraception during the study period and for 6 months after completing treatment with Debio 1347. Oral or injectable contraceptive agents cannot be the sole method of contraception. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Poorly controlled diabetes mellitus or hypertension (e.g., systolic > 180 mmHg or diastolic > 100 mmHg).
- Inability or unwillingness to swallow oral medications.
- Clinically significant gastrointestinal abnormality that would affect the absorption of drug such as gastrointestinal dysfunction, malabsorption syndrome, major resection of the small bowel or total gastrectomy or inflammatory bowel disease.
- Uncontrolled hydropericardium.
- Chemotherapy or radiotherapy within 14 days prior to starting study treatment. In case of monoclonal antibodies/biologics, within 28 days prior to starting study treatment.
- Administration of investigational agents within 28 days prior to treatment initiation.
- Major surgery and surgery for brain metastases within 28 days prior to screening start. Of note, Intravenous port placement is not considered as a major surgery.
- Not recovered from AEs or toxicities due to previous treatments to a Grade 1 or less specified in NCI-CTCAE version 4.0 excepting, albumin (< 2.5 g/dL), AST and ALT in patients with liver metastases (> 5 × ULN) ALP in patients with bone metastases (> 5 × ULN) and alopecia.
- Prior use of a drug targeting FGF or FGFR. Patients previously treated with medications that affect FGFR signaling as a secondary target (e.g., multi-tyrosine kinase inhibitors that primarily inhibit VEGF, but to a lesser extent also affect FGFR signaling) can be considered after discussion with the Principal Investigator.
- Currently under alcohol or drug abuse rehabilitation or treatment program.
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
- Eligibility Note: Patients could have progressed on prior aromatase inhibitors
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorioal Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase Ib/II Study of Debio 1347 Plus Fulvestrant in Patients With FGFR-Amplified Endocrine Receptor Positive Metastatic Breast Cancer
The purpose of a phase Ib study is to find out the best or maximum tolerated dose of a medication or combination of medications. Therefore, the purpose of this study is to decide the best dose of the study drug, Debio 1347, that can be given in combination with the standard hormonal drug, fulvestrant. Debio 1347 and fulvestrant could shrink the cancer but it could also cause side effects. This study tells us about the side effects of these drugs when given in this new combination, and how often they occur.
- Conditions
- Breast Cancer
- Being tested
- Fulvestrant, Debio 1347
- Keywords
- Debio 1347, Fulvestrant, 17-379
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FulvestrantDrug
Fulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter.
Debio 1347Drug
Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated.
| Study group | Role | What they receive |
|---|---|---|
| fulvestrant and Debio 1347 | Experimental | Fulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter. Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated. The dosage in the phase 2 portion will be the MTD/RP2D determined in the phase 1b portion. Receives: Drug: Fulvestrant; Drug: Debio 1347 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Experiencing Dose Limiting Toxicity
Selected non-hematologic and hematologic toxicities, as measured by the NCI CTCAE Version 4.0, will be described by frequency and grade, by cycle and over all cycles, with the maximum grade over all cycles used as the summary measure per patient.
Measured: 1 year
Proportion of Patients Who Have a Best Overall Response
Tumor response is based on the RECIST v.1.1.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start10 Nov 2017
- Primary completion12 Aug 2021
- Study completion12 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open-label, single institution, phase Ib/phase II non-randomized trial.
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Debiopharm International SA
- Responsible party
- Sponsor
- Investigators
- Komal Jhaveri, MD FACP, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03344536
- Sponsor's protocol ID
- 17-379
- Status last verified
- Aug 2021
- First submitted
- 14 Nov 2017
- Last updated
- 25 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of Debio 1347 Plus Fulvestrant in Patients With FGFR-Amplified Endocrine Receptor Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT03344536
- Acronym / sponsor ID
- 17-379
- Conditions
- Breast Cancer
- Keywords
- Debio 1347, Fulvestrant, 17-379
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Debiopharm International SA
- Study start
- 10 Nov 2017 (actual)
- Primary completion
- 12 Aug 2021 (actual)
- Study completion
- 12 Aug 2021 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Posted 25 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of a phase Ib study is to find out the best or maximum tolerated dose of a medication or combination of medications. Therefore, the purpose of this study is to decide the best dose of the study drug, Debio 1347, that can be given in combination with the standard hormonal drug, fulvestrant. Debio 1347 and fulvestrant could shrink the cancer but it could also cause side effects. This study tells us about the side effects of these drugs when given in this new combination, and how often they occur.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open-label, single institution, phase Ib/phase II non-randomized trial.
| Arm | Type | Receives |
|---|---|---|
| fulvestrant and Debio 1347 | Experimental | Drug: Fulvestrant, Drug: Debio 1347Fulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter. Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated. The dosage in the phase 2 portion will be the MTD/RP2D determined in the phase 1b portion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (35 listed)
- Males and Females Age > 18 years
- Written informed consent and authorization obtained from the subject/HIPAAappointed legal representative prior to performing any protocol-related procedures including screening evaluations
- Patients with metastatic histologically or cytologically confirmed invasive breast cancer
- Female patients of postmenopausal status. with metastatic histologically or cytologically confirmed invasive breast cancer.
- Postmenopausal status will be defined as following:
Key exclusion criteria (30 listed)
- Prior Fulvestrant for metastatic breast cancer will be allowed for phase 1 portion but not for the phase 2 portion
- History of hypersensitivity to any of the excipients in the Debio 1347 formulation (lactose hydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, sodium lauryl sulfate, and magnesium stearate).
- Other malignancies requiring active treatment in the last 6 months.
- Brain tumors and/or brain metastases unless they are asymptomatic, stable on recent imaging (not dated more than 30 days from the inclusion date), and have not required active treatment in the last 6 months.
- History and/or current evidence of endocrine alteration of calcium-phosphate homeostasis.
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 |
|---|---|---|
| FulvestrantFulvestrant will be administered according to its approved dose of 500 mg intramuscularly on days 1, 15, 29 and then every 28 days (+/-3 days) thereafter. | Drug | fulvestrant and Debio 1347 |
| Debio 1347Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated. | Drug | fulvestrant and Debio 1347 |
Primary outcome
Number of Patients Experiencing Dose Limiting Toxicity
Time frame: 1 year
Selected non-hematologic and hematologic toxicities, as measured by the NCI CTCAE Version 4.0, will be described by frequency and grade, by cycle and over all cycles, with the maximum grade over all cycles used as the summary measure per patient.
Proportion of Patients Who Have a Best Overall Response
Time frame: 1 year
Tumor response is based on the RECIST v.1.1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Komal Jhaveri, MD FACP principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fulvestrant and Debio 1347 in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
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 35 inclusion and 30 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 25 Nov 2022. 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 United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 25 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients Experiencing Dose Limiting Toxicity (time frame: 1 year). The study lists 2 primary outcomes in all. 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 25 Nov 2022; AzTrials last refreshed its copy on 7 Nov 2026.