Clinical Trials /

A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer

NCT03344536

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Debio 1347 Plus Fulvestrant in Patients With Metastatic Breast Cancer
  • Official Title: A Phase Ib/II Study of Debio 1347 Plus Fulvestrant in Patients With FGFR-Amplified Endocrine Receptor Positive Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-379
  • NCT ID: NCT03344536

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Fulvestrantfulvestrant and Debio 1347
Debio 1347fulvestrant and Debio 1347

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
fulvestrant and Debio 1347ExperimentalFulvestrant 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.
  • Fulvestrant
  • Debio 1347

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Postmenopausal female patients with metastatic histologically or cytologically
             confirmed invasive breast cancer. Pre or perimenopausal women allowed with the
             addition of goserelin.

          -  Postmenopausal status will be defined as following:

               -  Age ≥ 60 years

               -  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

          -  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 MSK-IMPACT assay. 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:

               -  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

               -  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) 72 × (serum creatinine in mg/dL)

          -  Patients with "treated and stable" brain lesions of 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.

        Exclusion Criteria:

          -  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.

          -  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 with positive pregnancy test result within 7 days of
             starting study treatment (any woman of childbearing potential who has menstruated
             within the year prior to enrolment will undergo pregnancy testing).

          -  Women of childbearing potential or men who is 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.

          -  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 Medical Monitor.

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients experiencing Dose Limiting Toxicity (Phase I)
Time Frame:1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Debio 1347
  • Fulvestrant
  • 17-379

Last Updated

November 14, 2017