Study of BCD-115 in Women With ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer

A Multicenter Open-label Non-comparative 2-Stage Phase 1a/1b Study to Assess the Safety and Pharmacokinetics of BCD-115 (JSC BIOCAD, Russia) in Combination With Endocrine Therapy in Women With ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer

A Multicenter Open-label Non-comparative 2-Stage Phase 1a/1b Study to Assess the Safety and Pharmacokinetics of Oral BCD-115 (JSC BIOCAD, Russia) in Combination with Endocrine Therapy in Women with ER(+) HER2(-) Local Advanced and Metastatic Breast Cancer

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: BCD-115

Detailed Description

Multicentre dose-finding open-label non-comparative phase Ia/Ib clinical trial for investigation of the safety, tolerability, pharmacokinetics of BCD-115 administered p.o. with intrapatient dose escalation in the population of patients with ER(+) HER2(-) advanced breast cancer in combination with a standard dose of endocrine therapy.

The trial will be conducted in two stages:

Stage 1 - finding of the maximum tolerated dose, determination of the recommended dose for Stage 2.

Stage 2 - study of the recommended dose from Stage 1 of BCD-115, analysis of tolerability and safety of selected dose/doses in additional cohorts, and determination of the estimated therapeutic dose/doses for further clinical studies.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Sankt Petersburg, Russian Federation, 196153
    • N.N. Blokhin Russian Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Written informed consent and ability to follow the Protocol procedures;
2. Age ≥18 years;
3. Female gender;
4. Postmenopausal status (Prior bilateral surgical oophorectomy; or medically confirmed post-menopausal status defined as spontaneous cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause);
5. Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease;
6. Progression of advanced breast cancer on first line endocrine therapy for advanced breast cancer.
7. ER positive tumor ≥ 10%;
8. HER2 negative breast cancer by FISH or IHC;
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 -2
10. Measurable disease according to RECIST 1.1 (only bone disease is not allowed)
11. Resolution of all acute toxic effects of prior therapy (including endocrine therapy) or surgical procedures to CTCAE grade ≤1
12. Adequate organ function;
13. Life expectancy - 12 weeks or more from the moment of randomization

Exclusion Criteria:

1. HER2-positive tumour ;
2. Patients with unstable brain metastases, advanced, symptomatic, visceral spread disease, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions pleural, pericardial, peritoneal, pulmonary lymphangitis, and over 50% liver involvement).
3. Important cardiovascular events in the past 6 months to randomization;
4. GI diseases which may affect the absorption of the study drug;
5. Inadequate hematopoietic function: neutrophils ≤1500/mm3, platelets ≤100 000/mm3,or hemoglobin ≤90 g/L;
6. Inadequate renal function: creatinine level ≥ 1.5 × upper limit of normal (ULN);
7. Inadequate liver function: bilirubin level ≥ 1.5 × ULN, AST and ALT levels ≥ 2.5 × ULN (5 × ULN for patients with liver metastases), alkaline phosphatase level ≥ 5 × ULN;
8. Concurrent antitumor treatment 21 days before randomization (surgery, radiation therapy; chemotherapy, except endocrine therapy);
9. Any other concomitant cancer including contralateral breast cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;
10. Conditions limiting patient's adherence to protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);
11. Concomitant participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;
12. Acute or active chronic infections;
13. HCV, HBV, HIV or syphilis infections;
14. Obstacles to p.o. administration of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: BCD-115 in dose escalation regimen; BCD-115 will be administered p.o. with intrapatient dose escalation in the population of patients with ER(+) HER2(-) advanced breast cancer in combination with a standard dose of endocrine therapy.	Drug: BCD-115; Inhibitor of CDK8/19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC0-t)	To determine AUC0-t after single doses of BCD-115 p.o. administration with dose escalation;	90 days
Peak Plasma Concentration (Cmax)	To determine observed maximum concentration in plasma or serums after single doses of BCD-115 p.o. administration with dose	90 days
The incidence and severity of AEs	The incidence and severity of AEs (%) related with the therapy based on results of review by 3 experts (%)	90 days
The incidence of grade 3-4 AEs	The incidence of grade 3-4 AEs (%) related with the therapy based on results of review by 3 experts	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment discontinuation due to adverse events	Treatment discontinuation due to adverse events (%)	90 days

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): March 1, 2018
• Study Completion (ACTUAL): March 1, 2018

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (ACTUAL): February 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2018
• Last Update Submitted That Met QC Criteria: March 11, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BCD-115-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No