Clinical Trials /

Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)

NCT02435680

Description:

To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and gemcitabine (carbo/gem) in advanced TNBC patients

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
MCS110Arm 1: MCS110+carboplatin+gemcitabine
carboplatinArm 1: MCS110+carboplatin+gemcitabine
gemcitabineArm 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

NameTypeDescriptionInterventions
Arm 1: MCS110+carboplatin+gemcitabineExperimentalMCS110+carboplatin+gemcitabine
  • MCS110
  • carboplatin
  • gemcitabine
Arm 2: carboplatin+gemcitabineActive Comparatorcarboplatin+gemcitabine
  • 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