A Phase 1 Study of IXAZOMIB in Adult Patients With Advanced Nonhematologic Malignancies

NCT00830869 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: C16001U1111-1206-2180
• Study Type: interventional
• Target: 116
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

Advanced Non-hematologic Malignancies

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (4)

• Part 1: Number of Participants With Dose Limiting Toxicity (DLT)

  Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0. DLT is any of following related to ixazomib:Grade (GR) 4 neutropenia (absolute neutrophil count\<500 cells/cubic meter\[cells/mm\^3\])for\>7 days; GR 3 neutropenia with coincident fever and/or infection; GR 4 thrombocytopenia (platelets \<25,000 cells/mm3)for\>7 days; GR 3 thrombocytopenia with clinically significant bleeding; Platelet count\<10,000 cells/mm3; GR 3 peripheral neuropathy;\>=GR 3 nausea/emesis in absence of optimal antiemetic therapy; \>=GR 3 diarrhoea in absence of optimal supportive therapy;GR 3 QTc prolongation noted on average of 3 electrocardiograms (ECGs);\>=GR 3 nonhematological toxicity except GR 3 arthralgia/myalgia or GR 3 fatigue for\<1 week; Delay in initiation of subsequent therapy cycle by\>7 days due to treatment-related toxicity Other\>=GR 2 nonhematological toxicity that opinion of investigator, requires discontinuation of therapy with Ixazomib.

  Part 1: Cycle 1 Day 1 up to Cycle 1 Day 21

• Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs)

  Part 1: Cycle 1 Day 1 up to Cycle 10 Day 41; Part 2: Cycle 1 Day 1 up to Cycle 12 Day 41

• Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities

  Day 1 up to 30 days after last dose of study drug (Cycle 12 Day 41)

• Number of Participants With Clinically Significant Change From Baseline in Vital Signs

  Vital sign measurements included diastolic and systolic blood pressure, heart rate, weight and oral temperature.

  Day 1 up to 30 days after last dose of study drug (Cycle 12 Day 41)

Secondary Outcomes (10)

• Part 1: AUC (0-72): Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours Post-dose for Ixazomib

  Part 1: Cycle 1 Days 1 and 11: pre-dose and at multiple time points (up to 72 hours) post-dose

• Part 1: C0: Initial Plasma Concentration After Bolus Intravenous Administration

  Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

• Part 1: Rac: Accumulation Ratio for Ixazomib

  Cycle 1 Day 11 pre-dose and at multiple time points (up to 72 hours) post-dose

• Part 1: Terminal Phase Elimination Half-life (T1/2) for Ixazomib

  Part 1: Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

• Part 1: E Max: Maximum Observed Effect for Ixazomib

  Part 1: Cycle 1 Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Cycle 1 Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose

Study Arms (12)

Part 1: Ixazomib 0.125 milligram per square meter (mg/m^2)

EXPERIMENTAL

Ixazomib (MLN9708) 0.125 mg/m\^2, injection, intravenously (IV), once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study.

Drug: IXAZOMIB

Part 1: Ixazomib 0.25 mg/m^2

EXPERIMENTAL

Ixazomib (MLN9708) 0.25 mg/m\^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study.

Drug: IXAZOMIB

Part 1: Ixazomib 0.5 mg/m^2

EXPERIMENTAL

Ixazomib (MLN9708) 0.5 mg/m\^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study.

Drug: IXAZOMIB

Part 1: Ixazomib 1 mg/m^2

EXPERIMENTAL

Ixazomib (MLN9708) 1 mg/m\^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study.

Drug: IXAZOMIB

Part 1: Ixazomib 1.33 mg/m^2

EXPERIMENTAL

Ixazomib (MLN9708) 1.33 mg/m\^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study.

Drug: IXAZOMIB

Part 1: Ixazomib 1.76 mg/m^2

EXPERIMENTAL

Ixazomib (MLN9708) 1.76 mg/m\^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study.

Drug: IXAZOMIB

Part 1: Ixazomib 2.34 mg/m^2

EXPERIMENTAL

Ixazomib (MLN9708) 2.34 mg/m\^2, injection, IV, once on Day 1, 4, 8 and 11 followed by 10 days of rest in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity during Part 1 of the study. Once the MTD will be established, participants with NSCLC, Head and Neck Cancer (H\&N), Soft Tissue Sarcoma (STC) or Prostate Cancer (PC) will be included in MTD disease expanded cohort. An additional tumor pharmacodynamics expansion cohort (TPEC) will enroll participants with any type of solid tumor that can be biopsied for tissue analysis before and after treatment with ixazomib.

Drug: IXAZOMIB

Part 2:Ixazomib 1.76 mg/m^2-NSCLC

EXPERIMENTAL

Ixazomib (MLN9708) 1.76 mg/m\^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with NSCLC during Part 2 of the study.

Drug: IXAZOMIB

Part 2: Ixazomib 1.76 mg/m^2-H&N

EXPERIMENTAL

Ixazomib (MLN9708) 1.76 mg/m\^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with H\&N during Part 2 of the study.

Drug: IXAZOMIB

Part 2: Ixazomib 1.76 mg/m^2-STC

EXPERIMENTAL

Ixazomib (MLN9708) 1.76 mg/m\^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with STC during Part 2 of the study.

Drug: IXAZOMIB

Part 2: Ixazomib 1.76 mg/m^2-PC

EXPERIMENTAL

Ixazomib (MLN9708) 1.76 mg/m\^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with PC during Part 2 of the study.

Drug: IXAZOMIB

Part 2: Ixazomib 1.76 mg/m^2-TPEC

EXPERIMENTAL

Ixazomib (MLN9708) 1.76 mg/m\^2, injection, IV, once on Day 1, 4, 8, and 11 followed by 10 days of rest period in 21-day treatment cycles for a maximum of 12 cycles, or until progressive disease or unacceptable toxicity in participants with various types of solid tumors suitable for biopsy in tumor pharmacodynamic expansion cohort (TPEC) during Part 2 of the study.

Drug: IXAZOMIB

Interventions

IXAZOMIB DRUG

All participants will receive IXAZOMIB IV injection on Days 1, 4, 8, and 11 of each treatment cycle followed by a rest period of 10 days. The first stage of the study will be initiated at a starting dose of 0.125 mg/m\^2. Subsequent doses will increase until a maximum tolerated dose (MTD) is established.

Part 1: Ixazomib 0.125 milligram per square meter (mg/m^2); Part 1: Ixazomib 0.25 mg/m^2; Part 1: Ixazomib 0.5 mg/m^2; Part 1: Ixazomib 1 mg/m^2; Part 1: Ixazomib 1.33 mg/m^2; Part 1: Ixazomib 1.76 mg/m^2; Part 1: Ixazomib 2.34 mg/m^2; Part 2: Ixazomib 1.76 mg/m^2-H&N; Part 2: Ixazomib 1.76 mg/m^2-PC; Part 2: Ixazomib 1.76 mg/m^2-STC; Part 2: Ixazomib 1.76 mg/m^2-TPEC; Part 2:Ixazomib 1.76 mg/m^2-NSCLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 .

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (7)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Washington- Seattle Cancer Care

Seattle, Washington, 98109, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Interventions

ixazomib

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2009
• First Posted: January 28, 2009
• Study Start: March 2, 2009
• Primary Completion: April 20, 2012
• Study Completion: April 20, 2012
• Last Updated: September 9, 2019
• Results First Posted: September 9, 2019

Record last verified: 2019-07

Locations

US (6); CA (1)