A study evaluating if the addition of MCS110 increases the efficacy of chemotherapy in women with disseminated breast cancer that is not dependent on hormones

• Register: EUCTR
• Last refreshed on: 6 April 2020
• Main ID: EUCTR2015-000179-29-AT
• Date of registration: 23/04/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A study evaluating if the addition of MCS110 increases the efficacy of chemotherapy in women with disseminated breast cancer that is not dependent on hormones
• Scientific title: A randomized phase II study of MCS110 combined with carboplatin and gemcitabine in advanced Triple Negative Breast Cancer (TNBC)
• Date of first enrolment: 05/06/2015
• Target sample size: 78
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000179-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Other specify the comparator: carboplatin , gemcitabine; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Czech Republic, France, Germany, Hong Kong, Korea, Republic of, Spain, Taiwan, Turkey, United States

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
- Adult women (= 18 years of age) with advanced TNBC.
- Histological or cytological evidence of estrogen-receptor negative (ER-), progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptor negative (HER2-) BC by local laboratory testing, based on last available tumor tissue.
- ER/PgR negativity to follow local guidelines
- If IHC HER2 2+, a negative FISH test is required
A pre-treatment tumor biopsy demonstrating high TAM content as assessed per the central laboratory (approximately 15% of TAMs or above).
- Patients must have:
- At least one measurable lesion per RECIST 1.1. (Note: Measurable lesions include lytic or mixed (lytic + blastic) bone lesions, with an identifiable soft tissue component that meets the measurability criteria)
or
- Bone lesions: non-measurable lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above. Patients with only non-measurable lesions (e.g. pleural effusion, ascites) and no lytic or mixed bone lesions are not eligible.

Other inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion criteria:
- Prior chemotherapy for advanced BC. Previous adjuvant/neoadjuvant chemotherapy is allowed.
- Therapy for underlying malignancy within 2 weeks prior to start of study treatment:
- Chemotherapy, biologic therapy (antibodies and biologically targeted small molecules)
- Radiotherapy
- Major surgery
- Patients receiving concomitant immunosuppressive agents or chronic corticosteroids (=10 mg of prednisone or equivalent) at the time of first dose of study drug.
- Known history of human immunodeficiency virus or active infection with hepatitis virus or any uncontrolled active systemic infection.
- Patients with the following laboratory values during screening and on Day 1 pre-dose:
- Absolute Neutrophil Count (ANC) < 1.0x109/L
- Hemoglobin < 9 g/dL
- Platelets < 100x109/L
- Serum creatinine > 1.5 x ULN
- Serum total bilirubin > 1.5 x ULN
- AST/SGOT and ALT/SGPT > 3.0 x ULN

Other exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Advanced Triple Negative Breast Cancer
MedDRA version: 20.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MCS110
Product Code: MCS110
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: not yet defined
Current Sponsor code: MCS110
Other descriptive name: MCS110
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Carboplatin Accord 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Product Name: Carboplatin Accord
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: carboplatin
Other descriptive name: CARBOPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Gemcitabin Accord 100 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Product Name: Gemcitabin Accord
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Other descriptive name: Gemzar
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 38-

Primary Outcome(s)

Main Objective: To assess the anti-tumor activity of MCS110 combined with carboplatin/gemcitabine (carbo/gem) compared to carbo/gem alone.

Timepoint(s) of evaluation of this end point: Tumor evaluation at sreening and then every six weeeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8).

Primary end point(s): PFS as per RECIST v1.1 (by local investigator assessment)

Secondary Objective: 1. Characterize the safety and tolerability of MCS110 given in combination with carbo/gem.
2. Characterize PK of MCS110 when combined with carbo/gem.
3. Characterize PK of carbo and gem in the presence and absence of MCS110.
4. Characterize PD effect of MCS110 when combined with carbo/gem
5. To assess the anti-tumor activity of MCS110 given in combination with carbo/gem as measured by additional efficacy measures.

Secondary Outcome(s)

Secondary end point(s): 1. Safety: adverse event (AEs), serious adverse events (SAEs) Tolerability: Dose interruptions, reductions and dose intensity
2. Serum concentration of free MCS110 and derived PK parameters
3. Plasma concentration of carboplatin, gemcitabine and dFdU (the primary metabolite of gem), and derived PK parameters
4. Total CSF-I circulating levels, serum CTX-I and circulating monocytes in blood. TAM and TIL content in pre- and post-dose tumor biopsies
5. Tumor response per RECIST v1.1 (by local investigator assessment):
Overall Response Rate (ORR), Duration of Response (DOR), Clinical Benefit Rate (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) = 6 months).

Timepoint(s) of evaluation of this end point: 1. Continuously
2. Please refer to protocol section 7
3. Please refer to protocol section 7
4. Please refer to protocol section 7
5. ORR:Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8).
DOR: Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8).
Clinical benefit rate: Tumor evaluation at screening and then every six weeks until the end of cycle 8. Thereafter every 9 weeks (after cycle 8).

Secondary ID(s)

2015-000179-29-CZ

CMCS110Z2201

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 15/05/2015
Contact: