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

NCT03344536 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 17-379
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

Debio 1347; Fulvestrant; 17-379

Outcome Measures

Primary Outcomes (2)

• 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.

  1 year

• Proportion of Patients Who Have a Best Overall Response

  Tumor response is based on the RECIST v.1.1.

  1 year

Study Arms (1)

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.

Drug: Fulvestrant; Drug: Debio 1347

Interventions

Fulvestrant DRUG

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.

fulvestrant and Debio 1347

Debio 1347 DRUG

Debio 1347 will be administered orally daily (1 cycle is 28 days) and the dose of Debio 1347 could be deescalated.

fulvestrant and Debio 1347

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Breast cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Debiopharm International SA: collaborator

Study Sites (1)

Memorioal Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant; CH5183284

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Komal Jhaveri MD
• Organization: Memorial Sloan Kettering Cancer Center

jhaverik@mskcc.org

646-888-5145

Study Officials

• Komal Jhaveri, MD FACP

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, single institution, phase Ib/phase II non-randomized trial.

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: November 17, 2017
• Study Start: November 10, 2017
• Primary Completion: August 12, 2021
• Study Completion: August 12, 2021
• Last Updated: November 25, 2022
• Results First Posted: November 25, 2022

Record last verified: 2021-08

Locations

US (1)