Ixazomib (MLN9708) in combination with carboplatin in pretreated women with advanced triple negative breast cancer (CARIXA)

Phase 1

Conditions: Advanced (locally advanced inoperable or metastatic) triple negative breast cancer progressing after first-line therapy
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-001421-13-AT

Lead Sponsor: AGMT gGmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 53

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 or very weak staining for estrogen receptor (IHC <10%), progesterone receptor (IHC <10%) and HER2/neu (IHC 0-1+, or 2+ if FISH-test is negative, 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•Signed informed consent prior to any study-specific procedure, with the understanding that consent may be withdrawn at any time without prejudice to future medical care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
•Women of childbearing potential must have a negative pregnancy test at screening and agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug OR agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.
•At least one prior line of chemotherapy for metastatic or locally advanced disease or disease progression within 12 months of completion of (neo-)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:
Hematologic:ANC (absolute neutrophil count) = 1.5 x 109/L
Hemoglobin = 8 g/dL
Platelets = 100 x 109/L
Liver Function: Albumin = 2.5 g/dL
Serum bilirubin = 2 mg/dL
AST and ALT = 3 x ULN without liver metastases and = 5 x ULN with documented liver metastases
Renal Function:Serum creatinin = 1.5 mg/dL or calculated creatinin clearance = 50

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

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 HIV 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •Phase I: Determination of maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs)<br>•Phase II: Overall response rate (ORR);Secondary Objective: •Safety profile<br>•Overall response rate<br>•Clinical benefit rate <br>•Progression-free survival (PFS)<br>•Quality of Life (EORTC QLQ-C30 and EORTC QLQ-BR23);Primary end point(s): Phase I: Determination of maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs)<br>Phase II: Overall response rate (ORR)<br>;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated when applicable data for all patients are available

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Phase I<br>•Safety profile<br>•Overall response rate<br>•Clinical benefit rate (CR, PR or stable disease for at least 24 weeks)<br>•Progression-free survival (PFS)<br>•Quality of Life (EORTC QLQ-C30 and EORTC QLQ-BR23)<br><br>Phase II<br>•Clinical benefit rate (CR, PR or stable disease for at least 24 weeks)<br>•Progression-free survival (PFS)<br>•Safety profile<br>•Quality of Life (EORTC QLQ-C30 and EORTC QLQ-BR23)<br>;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated when applicable data for all patients are available

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