Phase 1
Completed N=23
A Phase 1 Study of IXAZOMIB in Adult Patients With Advanced Nonhematologic Malignancies
Advanced Non-hematologic Malignancies
Source: ClinicalTrials.gov NCT00830869 ↗
Enrolled (actual)
23
Serious AEs
46.6%
Results posted
Sep 2019
Primary outcomePrimary: Part 1: Number of Participants With Dose Limiting Toxicity (DLT) — 0; 0; 0; 1 participants
Summary
This is an open-label, multicenter, phase 1, dose escalation study of IXAZOMIB. The primary purpose of this study is to determine the safety profile, establish the maximum tolerated dose, and inform the phase 2 dose of IXAZOMIB administered intravenously in participants with nonhematologic malignancies.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Dose Limiting Toxicity (DLT) |
0; 0; 0; 1; 0; 1 | — |
| PRIMARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs) |
1; 1; 1; 7; 4; 6 | — |
| PRIMARY Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities |
0; 0; 0; 2; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib |
91.6; 191.87; 391.46; 522.74; 620.0; 60.9 | — |
| SECONDARY Part 1: C0: Initial Plasma Concentration After Bolus Intravenous Administration |
15.1; 82.5; 192.0; 346.70; 366.16; 579.54 | — |
| SECONDARY Part 1: Rac: Accumulation Ratio for Ixazomib |
2.210; 5.160; 3.290; 2.996; 2.831; 3.086 | — |
| SECONDARY Part 1: Terminal Phase Elimination Half-life (T1/2) for Ixazomib |
171.90; 144.69; 104.84; 90.80 | — |
| SECONDARY Part 1: E Max: Maximum Observed Effect for Ixazomib |
7.70; 17.90; 28.20; 35.22; 46.73; 62.20 | — |
| SECONDARY Part 1: TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib |
1.000; 0.100; 0.250; 0.100; 0.250; 0.080 | — |
| SECONDARY Number of Participants With Best Overall Response |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 2: Ixazomib Concentration in Postdose Clinical Tumor Samples in Ixazomib 1.76 mg/m^2-TPEC |
525 | — |
| SECONDARY 20S Proteasome Activity of Ixazomib in the Tumor Tissue |
— | — |
| SECONDARY Expression of Biomarker (ATF-3) in Tumor Tissue |
— | — |
Eligibility Criteria
Inclusion Criteria
Each participant must meet all of the following inclusion criteria to be enrolled in the study:
- Male or female participants 18 years or older.
- Eastern Cooperative Oncology Group performance status 0-2.
- A diagnosis of a nonhematologic malignancy for which standard treatment is no longer effective. In the expanded cohort, enrollment will be limited to participants with a diagnosis of NSCLC, H&N cancer (squamous cell cancer), STS, or PC.
- Suitable venous access for pharmacokinetic (PK) and pharmacodynamic evaluations.
- Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
Male participants who agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
- Voluntary written consent must be obtained.
- Adequate clinical laboratory values during the screening period.
- In the escalation portion of the study, radiographically or clinically evaluable tumor was required, but measurable disease as defined by response evaluation criteria in solid tumors (RECIST) criteria was not required. In the MTD disease expansion cohorts and the TPEC, clinically measurable disease as defined by RECIST criteria was required for evaluation of NSCLC, H&N cancer, and STS. Prostate specific antigen (PSA) alone was acceptable for evaluation of PC.
- For participants in the TPEC, tumor tissue that, in the opinion of the investigator, could have been safely biopsied using a core needle.
Exclusion Criteria
Participants meeting any of the following exclusion criteria are not to be enrolled in the study:
- Peripheral neuropathy greater than or equal to (>=) Grade 2.
- Female participants who are lactating or have a positive serum pregnancy test during the screening period.
- Major surgery within 14 days before the first dose of treatment.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
- Life-threatening illness unrelated to cancer.
- Diarrhea greater than (>) Grade 1 based on the National Cancer Institute Common Terminology .Criteria for Adverse Events (NCI CTCAE) categorization.
- Systemic antineoplastic therapy / or radiotherapy within 21 days before the first dose of study treatment.
- Systemic treatment with prohibited medications.
- Participant has symptomatic brain metastasis.
- Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months.
- QTc >470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period.
- Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C positive.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Treatment with any investigational products within 28 days before the first dose of study treatment.
- For participants in the TPEC and participants in the MTD disease expansion cohorts who gave informed consent to undergo tumor biopsy, ongoing anticoagulant therapy (example, aspirin, clopidogrel [Plavix ®], warfarin, or heparin) that cannot be held to permit tumor biopsy .
- Known allergy to boron or excipients.
Data sourced from ClinicalTrials.gov (NCT00830869). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.