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

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Advanced Non-hematologic Malignancies

Treatments: Drug: IXAZOMIB

Study type: Interventional

Funder types: Industry

Identifiers

NCT00830869

C16001

U1111-1206-2180 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 116 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

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

Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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116 participants in 12 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

Part 1: Ixazomib 0.25 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

Part 1: Ixazomib 0.5 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

Part 1: Ixazomib 1 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

Part 1: Ixazomib 1.33 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

Part 1: Ixazomib 1.76 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

Part 1: Ixazomib 2.34 mg/m^2

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

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

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

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

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

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

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

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

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB

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

Experimental group

Description:

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.

Treatment:

Drug: IXAZOMIB