Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Carboplatin

Ixazomib

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

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

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.

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.

Richard Greil, MD

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.

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.

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

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

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

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

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

Spots Global Cancer Trial Database for study group of medical tumor therapy (agmt)