AzTrials
AzTrials

Triple-Negative Breast CancerPhase 1/2NCT02993094

Ixazomib (MLN9708) in Combination With Carboplatin in Pretreated Women With Advanced Triple Negative Breast Cancer

A Phase 1/2 study testing Ixazomib and Carboplatin in people with Triple-Negative Breast Cancer, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 12 sites in Austria.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is an open-label phase I/II study for patients with advanced (locally advanced inoperable or metastatic) triple-negative breast cancer progressing after first-line therapy receiving ixazomib on days 1, 8, and 15 in combination with carboplatin on days 1, 8, and 15. Cycles will be repeated every four weeks. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Triple-Negative Breast Cancer
What is being tested?
Ixazomib and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
12 sitesAustria
Study dates
21 Nov 2016to 15 Aug 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Metastatic or locally advanced (without curative loco-regional treatment options with curative intention) adenocarcinoma of the breast, histologically confirmed
  • Triple-negative subtype defined as the absence of staining for estrogen receptor (IHC <1%), progesterone receptor (IHC <1%) and HER2/neu (IHC 1+ or ISH ratio of < 2.0 between Her2 gene copy number and centromere of chromosome 17 or a copy number of 4 or less)
  • Signed informed consent prior to any study-specific procedure, with the understanding that consent may be withdrawn at any time without prejudice to future medical care
  • Female patients, age ≥ 18 years
  • At least one prior line of chemotherapy for metastatic or locally advanced disease or disease progression within 12 months of completion of adjuvant chemotherapy
  • Documented disease progression
Show all 12Show fewer
  • At least one measurable lesion according to RECIST 1.1 criteria
  • Life expectancy of at least 12 weeks
  • Performance status ECOG 0-2
  • Adequate left ventricular ejection fraction at baseline, defined as LVEF ≥ 50% by either echocardiogram or MUGA
  • Peripheral neuropathy NCI CTCAE grade ≤ 1 or grade 2 if no pain on clinical examination
  • Adequate hematological, liver and renal function:

Who cannot join

  • Pregnant or lactating women
  • Serious medical or psychiatric disorders that would interfere with the patient's safety or informed consent
  • Clinically significant cardiovascular disease, requiring medication during the study and which might interfere with regularity of the study treatment, or not controlled by medication.
  • Radiation of the target lesion within the last 4 weeks prior to randomization
  • Prior radiation to ≥ 30% of bone marrow
  • Active bacterial, viral or fungal infection
Show all 15Show fewer
  • Known HCV infection
  • Patients with clinically apparent brain metastases or evidence of a spinal cord compression
  • Major surgery within 14 days before enrollment
  • Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
  • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial
  • Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
  • History of other malignancy; patients who have been disease-free for 5 years or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
  • Prior treatment with a platinum derivative (except in (neo-)adjuvant setting if breast cancer recurrence did not occur within 12 months after (neo-)adjuvant chemotherapy completion) and/or with a proteasome inhibitor
  • Known hypersensitivity to the study drugs

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Austria12 sites

  • Landeskrankenhaus Feldkirch, Innere Med. II, Interne E

    Feldkirch, Vorarlberg, 6807

  • Universitätsklinik für Innere Medizin Graz

    Graz, Styria, 8036

  • UK Graz: Universitätsklinik für Frauenheilkunde und Geburtshilfe, Klinische Abteilung für Gynäkologie

    Graz, 8036

  • Universitätsklinik für Frauenheilkunde Innsbruck

    Innsbruck, Tyrol, 6020

  • LKH Hochsteiermark: Department für Hämato-Onkologie

    Leoben, 8700

  • BHS Linz: Interne I: Internistische Onkologie, Hämatologie und Gastroenterologie

    Linz, A-4020

  • KUK Linz: Klinik für Interne 3 - Schwerpunkt Hämatologie und Onkologie

    Linz, A-4020

  • PMU Salzburg: Universitätsklinik für Innere Medizin III

    Salzburg, A-5020

  • Landeskrankenhaus Steyr, Innere Medizin II Onkologie

    Steyr, A-4400

  • AKH Wien Universitätsklinik für Frauenheilkunde: Klin. Abt. f. Allg. Gynäkologie und gynäkologische Onkologie

    Vienna, A-1090

  • Klinikum Kreuzschwestern Wels GmbH

    Wels, Upper Austria, A-4600

  • LK Wiener Neustadt: Innere Medizin, Hämatologie und internistische Onkologie

    Wiener Neustadt, 2700

Other trials in Austria

About this study

This is an open-label phase I/II study for patients with advanced (locally advanced inoperable or metastatic) triple-negative breast cancer progressing after first-line therapy receiving ixazomib on days 1, 8, and 15 in combination with carboplatin on days 1, 8, and 15. Cycles will be repeated every four weeks.

Read the detailed description

The phase I part of this study uses an alternate dose escalation accelerated titration design. In the accelerated dose-escalation phase a single-patient cohort per dose level will be enrolled, until one dose limiting toxicity (DLT) or 2 moderate toxicities are observed during cycle 1, or until dose level 4 is reached. At this dose level the cohort is expanded to three patients and dose escalation reverts to a conventional 3+3 escalation design.

DLTs are defined as inability to deliver the drug combination of ixazomib and carboplatin due to drug related toxicity.

The maximum-administered dose (MAD) is defined as the dose at which DLT occur in at least two of six patients treated at that dose level. The dose just below the MAD is considered the maximum-tolerated dose (MTD), providing that DLT is observed in fewer than two of six treated patients (or fewer than one third if more than six patients will be treated) at that dose level. Determination of MAD and MTD is based on DLT observed during the first treatment cycle.

Phase II:

After establishing MTD in phase I, accrual continues to evaluate the efficacy and safety of the combination. A total of 41 patients will be included (patients enrolled in the phase I part within the conventional dose escalation phase at the dose level considered as the MTD may be included).

All subjects will continue on study drugs until disease progression, unacceptable toxicity or treatment discontinuation for any other reason.

Being tested
Ixazomib, Carboplatin
Keywords
breast cancer, advanced triple negative, ixazomib, carboplatin, CARIXA, Study Group of Medical Tumor Therapy (AGMT)
Medical subject headings
Triple Negative Breast Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IxazomibDrug

    Also called MLN9708

    Cycles will be repeated every four weeks. All subjects will continue on study drug until disease progression, unacceptable toxicity or treatment discontinuation for any other reason.

  • CarboplatinDrug

    Cycles will be repeated every four weeks. Cycles will be repeated every four weeks. All subjects will continue on study drug until disease progression, unacceptable toxicity or treatment discontinuation for any other reason.

Study groups in NCT02993094
Study groupRoleWhat they receive
Ixazomib/CarboplatinExperimentalAccelerated dose-escalation phase with a single-patient cohort per dose level until defined DLT is observed during cycle 1, or until dose level 4 is reached. At this dose level the cohort is expanded to three patients and dose escalation reverts to a conventional 3+3 escalation design. Intervention (experimental): Ixazomib; po; 3mg escalated to 4mg; day 1, 8, 15 Intervention (backbone): AUC 1.5 escalated to AUC 2.5; day 1, 8, 15
Receives: Drug: Ixazomib; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD)

    Determination of maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs)

    Measured: From treatment start until MTD (12 months --> start Phase II Q3 2017)

Secondary outcomes (5)

  1. Safety profile based on adverse events evaluation

    Incidence, type, severity and consequences (e.g. study discontinuation) of an adverse event

    Measured: During study treatment + 28 day after last study drug (approximately 3 years)

  2. Overall response rate

    Measured: During study treatment every 8 weeks until progression + end of study treatment (approximately 3 years)

  3. Clinical benefit rate

    Complete remission, partial remission or stable disease for at least 24 weeks

    Measured: During study treatment every 8 weeks until progression + end of study treatment (approximately 3 years)

  4. Progression-free survival (PFS)

    Measured: During study treatment every 8 weeks until progression + end of study treatment (approximately 3 years)

  5. Quality of Life of MBC patients

    EORTC quality of life questionnaire (QLQ-C30 and QLQ-BR23)

    Measured: Baseline + every 8 weeks until progression + at end of study treatment (approximately 3 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Dec 2016 (estimated)
  2. Study start21 Nov 2016
  3. Primary completion15 Aug 2020
  4. Study completion15 Aug 2020

Why it stopped: Due to slow recruitment, the study had to be terminated prematurely.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02993094
Sponsor's protocol ID
AGMT_MBC-10 (X16087)
Other IDs
2016-001421-13, 2016
Status last verified
Nov 2020
First submitted
4 Dec 2016
Last updated
30 Nov 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Rinnerthaler G, Gampenrieder SP, Petzer A, Burgstaller S, Fuchs D, Rossmann D, Balic M, Egle D, Rumpold H, Singer CF, Bartsch R, Petru E, Melchardt T, Ulmer H, Mlineritsch B, Greil R. Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial). BMC Cancer. 2018 Nov 6;18(1):1074. doi: 10.1186/s12885-018-4979-0.

    PubMed 30400780

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ixazomib and Carboplatin in people with Triple-Negative Breast Cancer, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 12 sites in Austria.

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 12 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: stopped early, as of the sponsor's last update on 30 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Austria. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was stopped early (reason given: Due to slow recruitment, the study had to be terminated prematurely.). Results are not available in the source record.

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?

Maximum tolerated dose (MTD) (time frame: From treatment start until MTD (12 months --> start Phase II Q3 2017)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02993094, which also lists 1 linked publication.

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 30 Nov 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in