A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Alisertib in Participants With Advanced Solid Tumors or Relapsed/Refractory Lymphoma

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors; Relapsed/Refractory Lymphoma

Treatments: Drug: Itraconazole; Drug: Alisertib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02259010

C14020

U1111-1161-5039 (Registry Identifier)

Details and patient eligibility

About

This study will assess the effect of multi-dose administration of itraconazole on the single-dose pharmacokinetics (PK) of alisertib.

Full description

The drug being tested in this study is called alisertib. Alisertib is being tested in adult participants with advanced solid tumors or relapsed refactory lymphoma. The study will look at the effect of the pharmacokinetics (how the drug moves through the body) of alisertib in the presence and absence of itraconazole.

This is an open label study. Participants will receive:

• Alisertib tablets 30 mg in Part A and 50 mg in Part B
• Itraconazole oral solution 200 mg in Part A

Participation in Part A is approximately 25 days. Part B participation is repeating 21-day cycles. The maximum duration of treatment with alisertib will be 12 months (approximately 16 cycles) unless it is determined by the investigator, with agreement by the sponsor, that a participant would derive clinical benefit from continued treatment beyond 12 months.

This multi-center study will take place in the United States.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Male and female participants 18 years of age or older.
2. Participants with histologic or cytologic diagnosis of advanced or metastatic solid tumors or lymphomas for which no curative or life-prolonging therapies exist.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria

1. Systemic treatment with moderate or strong CYP3A inhibitors or inducers must be discontinued at least 14 days before the first dose of alisertib, and the use of these agents is not permitted during the study (except for the protocol-specified administration of itraconazole).
2. Known gastrointestinal (GI) abnormality (including recurrent nausea or vomiting) or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib.
3. Known hypersensitivity or intolerance to itraconazole or similar class agents.

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg

Experimental group

Description:

All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).

Treatment:

Drug: Alisertib

Drug: Itraconazole