Advanced Triple Negative Breast Cancer (TNBC) With High TAMsPhase 2TNBCNCT02435680
Efficacy Study of MCS110 Given With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
A Phase 2 study testing MCS110, carboplatin and gemcitabine in people with Advanced Triple Negative Breast Cancer (TNBC) With High TAMs, run by Novartis Pharmaceuticals at 23 sites in 12 countries.
Trial summary
To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and gemcitabine (carbo/gem) in advanced TNBC patients Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Advanced Triple Negative Breast Cancer (TNBC) With High TAMs
- What is being tested?
- MCS110, carboplatin and gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 23 sitesin 12 countries
- Study dates
- 10 Aug 2015to 23 Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Show all 15Show fewer
- 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
Trial locations and contacts
23 sites in 12 countries.
23 sites in 12 countries
Spain4 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, 08041
Novartis Investigative Site
Madrid, 28050
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706
Austria3 sites
Novartis Investigative Site
Salzburg, 5020
Novartis Investigative Site
Vienna, 1090
Novartis Investigative Site
Vienna, A-1090
Germany3 sites
Novartis Investigative Site
Berlin, 10967
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Essen, 45136
United States2 sites
Massachusetts General Hospital Cancer Center SC
Boston, Massachusetts, 02114
Highlands Oncology Group
Fayetteville, Arkansas, 72703
France2 sites
Novartis Investigative Site
Paris, 75231
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Italy2 sites
Novartis Investigative Site
Bologna, 40138
Novartis Investigative Site
Naples, 80131
South Korea2 sites
Novartis Investigative Site
Seoul, Korea, 05505
Novartis Investigative Site
Seoul, 03080
Australia1 site
Novartis Investigative Site
Nedlands, Western Australia, 6009
About this study
Official title: A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and gemcitabine (carbo/gem) in advanced TNBC patients
- Being tested
- MCS110, carboplatin, gemcitabine
- Keywords
- MCS110; carboplatin; gemcitabine; TNBC; TAMs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MCS110Drug
taken by I.V
carboplatinDrug
taken by I.V
gemcitabineDrug
taken by I.V
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: MCS110+carboplatin+gemcitabine | Experimental | MCS110+carboplatin+gemcitabine Receives: Drug: MCS110; Drug: carboplatin; Drug: gemcitabine |
| Arm 2: carboplatin+gemcitabine | Active comparator | carboplatin+gemcitabine Receives: Drug: carboplatin; Drug: gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 years
Secondary outcomes (12)
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
Measured: day 21 (end cycle 1); day 84 (end cycle 4)
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax
Measured: day 21 (end cycle 1); day 84 (end cycle 4)
Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
day 21 (end cycle 1); day 84 (end cycle 4)
Measured: day 21, day 84
AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
day 21 (end cycle 1); day 84 (end cycle 4)
Measured: day 21, day 84
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.
Measured: baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148
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.
Measured: baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148
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.
Measured: 4 years
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.
Measured: 4 years
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
Measured: 4 years
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%
Measured: 4 years
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
Measured: Baseline, Day 29-43
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.
Measured: day 15, 29, 43, 50
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study start10 Aug 2015
- Primary completion4 Jan 2020
- Study completion23 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Triple Negative Breast Cancer (TNBC) With High TAMsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02435680
- Sponsor's protocol ID
- CMCS110Z2201
- Other IDs
- 2015-000179-29, 2015
- Acronym
- TNBC
- Status last verified
- May 2021
- First submitted
- 22 Apr 2015
- Last updated
- 21 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC)
- ClinicalTrials.gov ID
- NCT02435680
- Acronym / sponsor ID
- TNBC / CMCS110Z2201
- Keywords
- MCS110; carboplatin; gemcitabine; TNBC; TAMs
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 10 Aug 2015 (actual)
- Primary completion
- 4 Jan 2020 (actual)
- Study completion
- 23 Mar 2020 (actual)
- First posted
- 6 May 2015 (estimated)
- Results
- Posted 21 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine whether MCS110 antibody therapy improves the efficacy of carboplatin and gemcitabine (carbo/gem) in advanced TNBC patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: MCS110+carboplatin+gemcitabine | Experimental | Drug: MCS110, Drug: carboplatin, Drug: gemcitabineMCS110+carboplatin+gemcitabine |
| Arm 2: carboplatin+gemcitabine | Active comparator | Drug: carboplatin, Drug: gemcitabinecarboplatin+gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MCS110taken by I.V | Drug | Arm 1: MCS110+carboplatin+gemcitabine |
| carboplatintaken by I.V | Drug | Arm 1: MCS110+carboplatin+gemcitabine, Arm 2: carboplatin+gemcitabine |
| gemcitabinetaken by I.V | Drug | Arm 1: MCS110+carboplatin+gemcitabine, Arm 2: carboplatin+gemcitabine |
Primary outcome
Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment)
Time frame: 4 years
PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design.
12 secondary outcomes
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau
Time frame: day 21 (end cycle 1); day 84 (end cycle 4)
Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax
Time frame: day 21 (end cycle 1); day 84 (end cycle 4)
Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
Time frame: day 21, day 84
AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
Time frame: day 21, day 84
Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels
Time frame: baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148
Serum C-terminal Telopeptide of Type I Collagen (CTX-I)
Time frame: baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)
Time frame: 4 years
Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response
Time frame: 4 years
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
MCS110 Dose Intensity
Time frame: 4 years
Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.
Time frame: Baseline, Day 29-43
Circulating Monocytes Cells in Blood
Time frame: day 15, 29, 43, 50
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. 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
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
23 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MCS110, carboplatin and gemcitabine in people with Advanced Triple Negative Breast Cancer (TNBC) With High TAMs, run by Novartis Pharmaceuticals at 23 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Spain, Austria, Germany, United States, France and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment) (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2021.