Pharmacokinetics Study of Oral IXAZOMIB in Participants With Advanced Nonhematologic Malignancies or Lymphoma

Lymphoma Clinical Trial

Official title:

A Phase 1 Study of Oral IXAZOMIB (MLN9708) to Assess Relative Bioavailability, Food Effect, Drug-Drug Interaction With Ketoconazole, Clarithromycin or Rifampin; and Safety and Tolerability in Patients With Advanced Nonhematologic Malignancies or Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01454076
• Other study ID #: C16009
• Secondary ID: U1111-1183-0218
• Status: Completed
• Phase: Phase 1
• First received: October 13, 2011
• Last updated: June 16, 2017
• Start date: November 10, 2011
• Est. completion date: June 16, 2016

Study information

• Verified date: June 2017
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, sequential, 5-arm, phase 1 study of oral IXAZOMIB designed to assess drug-drug interaction with ketoconazole (Arm 1), the relative bioavailability of 2 capsule formulations of IXAZOMIB (Arm 2), food effect (Arm 3), drug-drug interaction with rifampin (Arm 4), and drug-drug interaction with clarithromycin (Arm 5) in participants with advanced nonhematologic malignancies or lymphoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: June 16, 2016
• Est. primary completion date: April 1, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female participants 18 years or older.

• Participants must have a diagnosis of histologically or cytologically confirmed metastatic and/or advanced solid tumor malignancy or lymphoma for which no effective standard treatment is available.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

• Female participants who are postmenopausal at least 1 year, or surgically sterile, or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time from the time of signing the consent form through 90 days after the last dose of study drug, or agree to practice true abstinence.

• Male participants, even if surgically sterilized, agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug or agree to practice true abstinence.

• Voluntary written informed consent.

• Clinical laboratory values as specified in protocol.

• Suitable venous access.

• Recovered (that is, less than [< ] Grade 1 toxicity or participant's baseline status) from the reversible effects of prior anticancer therapy.

Exclusion Criteria:

• Peripheral neuropathy greater than (>) Grade 2 on clinical examination.

• Systemic treatment with strong inhibitors of cytochrome P450 (CYP) 1A2, strong inhibitors of CYP3A, or strong CYP3A inducers or use of ginkgo biloba or St. John's wort within 14 days before the first dose of IXAZOMIB.

• Participant has symptomatic brain metastasis. Participants with brain metastases must:

have stable neurologic status following surgery or radiation for at least 2 weeks after completion of the definitive therapy; and be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

• Female participants who are pregnant or lactating.

• Serious illness that could interfere with protocol completion.

• Autologous stem cell transplant within 6 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.

• Prior treatment with rituximab or other unconjugated any antibody treatment within 42 days (21 days if there is clear evidence of progressive disease or immediate treatment is mandated).

• Ongoing treatment with corticosteroids.

• Radiotherapy within 21 days before the first dose of study drug.

• Major surgery within 14 days before the first dose of study drug.

• Infection requiring systemic antibiotic therapy or other serious infection within 14 days prior to first dose of study drug.

• Life-threatening illness unrelated to cancer.

• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive, or suspected hepatitis C infection.

• Diagnosis or treatment of another malignancy within 2 years preceding first dose, or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

• Evidence of uncontrolled cardiovascular conditions.

• QTc > 500 milliseconds on a 12-lead electrocardiogram (ECG).

• Known gastrointestinal disease or procedure that could interfere with the oral absorption or tolerance of IXAZOMIB including difficulty swallowing capsules; diarrhea > Grade 1 despite supportive therapy.

• Participants with gastric achlorhydria (Arm 1 only).

• Participants who have used any nicotine containing products within 14 days before the first dose of study drug (Arm 1, Arm 4, and Arm 5).

• Treatment with any investigational products or systemic antineoplastic therapies within 21 days before the first dose of IXAZOMIB.

• Participants with known hypersensitivity to macrolide antibiotics (example, clarithromycin, erythromycin, azithromycin) or a history of jaundice/liver injury during prior exposure to clarithromycin (Arm 5 only).

Related Conditions & MeSH terms

• Lymphoma
• Neoplasms
• Nonhematologic Malignancies

Intervention

Drug:
• Ixazomib 2.5 mg
Ixazomib 2.5 mg Capsule B (Cycle 1 only)
• Ixazomib 4 mg Capsule A
Ixazomib 4 mg Capsule A (Cycle 1 only)
• Ixazomib 4 mg Capsule B
Ixazomib 4 mg Capsule B (Cycle 2 and beyond )
• Ketoconazole
Ketoconazole 400 mg tablets (Cycle 1 only)
• Rifampin
Rifampin 600 mg capsule (Cycle 1 only)
• Clarithromycin
Clarithromycin 500 mg tablets (Cycle 1 only)
• Ixazomib 4 mg Capsule B
Ixazomib 4 mg Capsule B (Cycle 1 and beyond)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax: Maximum Observed Plasma Concentration for Ixazomib		Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hours[hrs])post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
Primary	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib		Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
Primary	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib		Arm 1:Days 1, 15 and Arm 5:Day 6 pre-dose and at multiple time points(up to 264 hrs)post-dose;Arm 2, 3:Days 1,15 pre-dose and at multiple time points(up to 216 hrs)post-dose;Arm 4:Day 8 pre-dose and at multiple time points(up to 168 hrs)post-dose
Secondary	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45)
Secondary	Number of Participants With Clinically Significant TEAEs Related to Laboratory Abnormalities		Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
Secondary	Number of Participants With Clinically Significant Vital Sign Abnormalities		Cycle 1 Day 1 up to 30 days after last dose of study drug (Arm 1 and 5: Cycle 19 Day 45; Arm 2: Cycle 7 Day 45; Arm 3: Cycle 22 Day 45; Arm 4: Cycle 25 Day 45
Secondary	Percentage of Participants With Best Overall Response	Best overall response for a participant is best observed post-baseline disease response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: Complete response (CR) was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 millimeter [mm]). No new lesions. Partial response (PR) was defined as greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD) was defined as not qualifying for CR, PR, Progressive Disease (PD). An increase of >=20% from the nadir (or baseline, if it represents the point at which the sum of target disease was lowest) represents PD.	Baseline up to end of treatment (approximately 1.9 years)