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

NCT ID: NCT00830869

Last Updated: 2019-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-02
• Study Completion Date: 2012-04-20

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 0.25 mg/m^2

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 0.5 mg/m^2

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 1 mg/m^2

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 1.33 mg/m^2

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 1.76 mg/m^2

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 2.34 mg/m^2

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 2:Ixazomib 1.76 mg/m^2-NSCLC

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.

Group Type: EXPERIMENTAL

IXAZOMIB

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

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 2: Ixazomib 1.76 mg/m^2-STC

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 2: Ixazomib 1.76 mg/m^2-PC

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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 2: Ixazomib 1.76 mg/m^2-TPEC

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.

Group Type: EXPERIMENTAL

IXAZOMIB

Intervention Type: 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.

Interventions

IXAZOMIB

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female participants 18 years or older.

2. Eastern Cooperative Oncology Group performance status 0-2.

3. 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.

4. Suitable venous access for pharmacokinetic (PK) and pharmacodynamic evaluations.

5. 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.

6. Voluntary written consent must be obtained.

7. Adequate clinical laboratory values during the screening period.

8. 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.

9. 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

1. Peripheral neuropathy greater than or equal to (>=) Grade 2.

2. Female participants who are lactating or have a positive serum pregnancy test during the screening period.

3. Major surgery within 14 days before the first dose of treatment.

4. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.

5. Life-threatening illness unrelated to cancer.

6. Diarrhea greater than (>) Grade 1 based on the National Cancer Institute Common Terminology .Criteria for Adverse Events (NCI CTCAE) categorization.

7. Systemic antineoplastic therapy / or radiotherapy within 21 days before the first dose of study treatment.

8. Systemic treatment with prohibited medications.

9. Participant has symptomatic brain metastasis.

10. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months.

11. QTc >470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period.

12. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C positive.

13. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

14. Treatment with any investigational products within 28 days before the first dose of study treatment.

15. 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 .

16. Known allergy to boron or excipients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Michigan

Ann Arbor, Michigan, United States

Duke University

Durham, North Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

University of Washington- Seattle Cancer Care

Seattle, Washington, United States

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

U1111-1206-2180

Identifier Type: OTHER

Identifier Source: secondary_id

C16001

Identifier Type: -

Identifier Source: org_study_id