Clinical Trials /

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

NCT02993094

Description:

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.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ixazomib (MLN9708) in Combination With Carboplatin in Pretreated Women With Advanced Triple Negative Breast Cancer
  • Official Title: Ixazomib (MLN9708) in Combination With Carboplatin in Pretreated Women With Advanced Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: AGMT_MBC-10 (X16087)
  • SECONDARY ID: 2016-001421-13
  • NCT ID: NCT02993094

Conditions

  • Triple-Negative Breast Cancer

Interventions

DrugSynonymsArms
IxazomibMLN9708Ixazomib/Carboplatin
CarboplatinIxazomib/Carboplatin

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
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
  • Ixazomib
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  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:

        Exclusion Criteria:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:From treatment start until MTD (12 months --> start Phase II Q3 2017)
Safety Issue:
Description:Determination of maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs)

Secondary Outcome Measures

Measure:Safety profile based on adverse events evaluation
Time Frame:During study treatment + 28 day after last study drug (approximately 3 years)
Safety Issue:
Description:Incidence, type, severity and consequences (e.g. study discontinuation) of an adverse event
Measure:Overall response rate
Time Frame:During study treatment every 8 weeks until progression + end of study treatment (approximately 3 years)
Safety Issue:
Description:
Measure:Clinical benefit rate
Time Frame:During study treatment every 8 weeks until progression + end of study treatment (approximately 3 years)
Safety Issue:
Description:Complete remission, partial remission or stable disease for at least 24 weeks
Measure:Progression-free survival (PFS)
Time Frame:During study treatment every 8 weeks until progression + end of study treatment (approximately 3 years)
Safety Issue:
Description:
Measure:Quality of Life of MBC patients
Time Frame:Baseline + every 8 weeks until progression + at end of study treatment (approximately 3 years)
Safety Issue:
Description:EORTC quality of life questionnaire (QLQ-C30 and QLQ-BR23)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arbeitsgemeinschaft medikamentoese Tumortherapie

Trial Keywords

  • breast cancer
  • advanced triple negative
  • ixazomib
  • carboplatin
  • CARIXA
  • Study Group of Medical Tumor Therapy (AGMT)

Last Updated

January 6, 2020