Description:
To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and
gemcitabine (carbo/gem) in advanced TNBC patients
Title
- Brief Title: Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
- Official Title: A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
Clinical Trial IDs
- ORG STUDY ID:
CMCS110Z2201
- SECONDARY ID:
2015-000179-29
- NCT ID:
NCT02435680
Conditions
- Advanced Triple Negative Breast Cancer (TNBC) With High TAMs
Interventions
Drug | Synonyms | Arms |
---|
MCS110 | | Arm 1: MCS110+carboplatin+gemcitabine |
carboplatin | | Arm 1: MCS110+carboplatin+gemcitabine |
gemcitabine | | Arm 1: MCS110+carboplatin+gemcitabine |
Purpose
To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and
gemcitabine (carbo/gem) in advanced TNBC patients
Trial Arms
Name | Type | Description | Interventions |
---|
Arm 1: MCS110+carboplatin+gemcitabine | Experimental | MCS110+carboplatin+gemcitabine | - MCS110
- carboplatin
- gemcitabine
|
Arm 2: carboplatin+gemcitabine | Active Comparator | carboplatin+gemcitabine | |
Eligibility 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-)
Breast Cancer 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
- 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)
Exclusion Criteria:
- Prior chemotherapy for advanced BC. Previous adjuvant/neoadjuvant chemotherapy is
allowed (carboplatin, cisplatin or gemcitabine only if > 12 months has passed since
last administration).
- 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 study dose.
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
screening.
- 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 predose:
- Absolute Neutrophil Count (ANC) < 1.5x109/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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. |
Secondary Outcome Measures
Measure: | Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau |
Time Frame: | day 21 (end cycle 1); day 84 (end cycle 4) |
Safety Issue: | |
Description: | AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days |
Measure: | Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax |
Time Frame: | day 21 (end cycle 1); day 84 (end cycle 4) |
Safety Issue: | |
Description: | |
Measure: | Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU) |
Time Frame: | day 21, day 84 |
Safety Issue: | |
Description: | day 21 (end cycle 1); day 84 (end cycle 4) |
Measure: | AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU) |
Time Frame: | day 21, day 84 |
Safety Issue: | |
Description: | day 21 (end cycle 1); day 84 (end cycle 4) |
Measure: | Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels |
Time Frame: | baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148 |
Safety Issue: | |
Description: | results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days. These Biomarker Analyses were performed for MCS110 treated patients only. |
Measure: | Serum C-terminal Telopeptide of Type I Collagen (CTX-I) |
Time Frame: | baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148 |
Safety Issue: | |
Description: | results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days.
Biomarker Analyses performed for MCS110 treated patients only. |
Measure: | Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) |
Time Frame: | 4 years |
Safety Issue: | |
Description: | CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. |
Measure: | Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response |
Time Frame: | 4 years |
Safety Issue: | |
Description: | CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. |
Measure: | Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption |
Time Frame: | 4 years |
Safety Issue: | |
Description: | patients treated with MCS110 only |
Measure: | MCS110 Dose Intensity |
Time Frame: | 4 years |
Safety Issue: | |
Description: | Relative dose intensity by categories.
Patients treated with MCS110 only. The dose intensity measures the dose actually taken versus the planned dose, and is expressed in percentage:
<50%: less than 50 % of the planned dose received; 50-<75 %: dose received is 50% or more, but less than 75 %; 75-<90 %: dose received is 75% or more, but less than 90%; 90-<110 %: dose received is 90% or more, but less than 110% |
Measure: | Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies. |
Time Frame: | Baseline, Day 29-43 |
Safety Issue: | |
Description: | results expressed as a the ratio change from baseline expressed in percentage: Biopsies were taken at baseline and between Day 29 and Day 43. Patients treated with MCS110 only |
Measure: | Circulating Monocytes Cells in Blood |
Time Frame: | day 15, 29, 43, 50 |
Safety Issue: | |
Description: | Cycle duration is 21 days results expressed in percentage of cells. Only 1 arm reported as results were available for 1 patient only. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- MCS110; carboplatin; gemcitabine; TNBC; TAMs
Last Updated
June 21, 2021