NCT02993094

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2016

Typical duration for phase_1

Geographic Reach
1 country

12 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 21, 2016

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

December 4, 2016

Completed
11 days until next milestone

First Posted

Study publicly available on registry

December 15, 2016

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 15, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2020

Completed
Last Updated

November 30, 2020

Status Verified

November 1, 2020

Enrollment Period

3.7 years

First QC Date

December 4, 2016

Last Update Submit

November 26, 2020

Conditions

Triple-Negative Breast Cancer

Keywords

breast canceradvanced triple negativeixazomibcarboplatinCARIXAStudy Group of Medical Tumor Therapy (AGMT)

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD)

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

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

Secondary Outcomes (5)

  • Safety profile based on adverse events evaluation

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

  • Overall response rate

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

  • Clinical benefit rate

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

  • Progression-free survival (PFS)

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

  • Quality of Life of MBC patients

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

Study Arms (1)

Ixazomib/Carboplatin

EXPERIMENTAL

Accelerated 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

Drug: IxazomibDrug: Carboplatin

Interventions

IxazomibDRUG

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.

Also known as: MLN9708
Ixazomib/Carboplatin
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.

Ixazomib/Carboplatin

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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:

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Universitätsklinik für Innere Medizin Graz

Graz, Styria, 8036, Austria

Location

Universitätsklinik für Frauenheilkunde Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Klinikum Kreuzschwestern Wels GmbH

Wels, Upper Austria, A-4600, Austria

Location

Landeskrankenhaus Feldkirch, Innere Med. II, Interne E

Feldkirch, Vorarlberg, 6807, Austria

Location

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

Graz, 8036, Austria

Location

LKH Hochsteiermark: Department für Hämato-Onkologie

Leoben, 8700, Austria

Location

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

Linz, A-4020, Austria

Location

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

Linz, A-4020, Austria

Location

PMU Salzburg: Universitätsklinik für Innere Medizin III

Salzburg, A-5020, Austria

Location

Landeskrankenhaus Steyr, Innere Medizin II Onkologie

Steyr, A-4400, Austria

Location

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

Vienna, A-1090, Austria

Location

LK Wiener Neustadt: Innere Medizin, Hämatologie und internistische Onkologie

Wiener Neustadt, 2700, Austria

Location

Related Publications (1)

  • 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.

    PMID: 30400780DERIVED

MeSH Terms

Conditions

Triple Negative Breast NeoplasmsBreast Neoplasms

Interventions

ixazomibCarboplatin

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic Chemicals

Study Officials

  • Richard Greil, MD

    PMU Salzburg: Universitätsklinik für Innere Medizin III

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 4, 2016

First Posted

December 15, 2016

Study Start

November 21, 2016

Primary Completion

August 15, 2020

Study Completion

August 15, 2020

Last Updated

November 30, 2020

Record last verified: 2020-11

Data Sharing

IPD Sharing
Will not share

Locations

AU(12)