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

Primary Purpose

Advanced Triple Negative Breast Cancer (TNBC) With High TAMs

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MCS110
carboplatin
gemcitabine
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Triple Negative Breast Cancer (TNBC) With High TAMs focused on measuring MCS110; carboplatin; gemcitabine; TNBC; TAMs

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Highlands Oncology Group
  • Massachusetts General Hospital Cancer Center SC
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm 1: MCS110+carboplatin+gemcitabine

Arm 2: carboplatin+gemcitabine

Arm Description

MCS110+carboplatin+gemcitabine

carboplatin+gemcitabine

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment)
PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design.

Secondary Outcome Measures

Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau
AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax
Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
day 21 (end cycle 1); day 84 (end cycle 4)
AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
day 21 (end cycle 1); day 84 (end cycle 4)
Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels
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.
Serum C-terminal Telopeptide of Type I Collagen (CTX-I)
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.
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)
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.
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response
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.
Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption
patients treated with MCS110 only
MCS110 Dose Intensity
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%
Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.
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
Circulating Monocytes Cells in Blood
Cycle duration is 21 days results expressed in percentage of cells. Only 1 arm reported as results were available for 1 patient only.

Full Information

First Posted
April 22, 2015
Last Updated
May 26, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02435680
Brief Title
Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
Acronym
TNBC
Official Title
A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
August 10, 2015 (Actual)
Primary Completion Date
January 4, 2020 (Actual)
Study Completion Date
March 23, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Triple Negative Breast Cancer (TNBC) With High TAMs
Keywords
MCS110; carboplatin; gemcitabine; TNBC; TAMs

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: MCS110+carboplatin+gemcitabine
Arm Type
Experimental
Arm Description
MCS110+carboplatin+gemcitabine
Arm Title
Arm 2: carboplatin+gemcitabine
Arm Type
Active Comparator
Arm Description
carboplatin+gemcitabine
Intervention Type
Drug
Intervention Name(s)
MCS110
Intervention Description
taken by I.V
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
taken by I.V
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Intervention Description
taken by I.V
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment)
Description
PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau
Description
AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days
Time Frame
day 21 (end cycle 1); day 84 (end cycle 4)
Title
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax
Time Frame
day 21 (end cycle 1); day 84 (end cycle 4)
Title
Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
Description
day 21 (end cycle 1); day 84 (end cycle 4)
Time Frame
day 21, day 84
Title
AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
Description
day 21 (end cycle 1); day 84 (end cycle 4)
Time Frame
day 21, day 84
Title
Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels
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.
Time Frame
baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148
Title
Serum C-terminal Telopeptide of Type I Collagen (CTX-I)
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.
Time Frame
baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148
Title
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)
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.
Time Frame
4 years
Title
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response
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.
Time Frame
4 years
Title
Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption
Description
patients treated with MCS110 only
Time Frame
4 years
Title
MCS110 Dose Intensity
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%
Time Frame
4 years
Title
Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.
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
Time Frame
Baseline, Day 29-43
Title
Circulating Monocytes Cells in Blood
Description
Cycle duration is 21 days results expressed in percentage of cells. Only 1 arm reported as results were available for 1 patient only.
Time Frame
day 15, 29, 43, 50

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Highlands Oncology Group
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center SC
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Novartis Investigative Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Novartis Investigative Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Novartis Investigative Site
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75231
Country
France
Facility Name
Novartis Investigative Site
City
Saint-Herblain Cédex
ZIP/Postal Code
44805
Country
France
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10967
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45136
Country
Germany
Facility Name
Novartis Investigative Site
City
Hong Kong SAR
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Santiago de Compostela
State/Province
Galicia
ZIP/Postal Code
15706
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
35100
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Learn more about this trial

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

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