Pharmacokinetics of Alisertib in Adults With Advanced Solid Tumors or Relapsed/Refractory Lymphoma With Varying Degrees of Hepatic Function

NCT02214147 | Completed Phase 1 Results

• 2 other identifiers: C14019U1111-1155-6072
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the effect of moderate or severe hepatic impairment on the single-dose pharmacokinetics of alisertib in adult participants with cancer.

Conditions

Advanced Solid Tumors; Relapsed/Refractory Lymphoma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (3)

• Unbound Cmax: Maximum Observed Plasma Concentration for Alisertib

  Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose

• Unbound AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib

  Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose

• Unbound AUC0-∞: Area Under the Concentration-Time Curve From Time 0 to Infinity for Alisertib

  Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose

Secondary Outcomes (8)

• Percentage of Participants Who Experienced at Least 1 Treatment-Emergent Adverse Event

  Baseline to 30 days after last dose (Up to 312 Days)

• Percentage of Participants Who Experienced at Least 1 Serious Adverse Event

  Baseline to 30 days after last dose (Up to 312 Days)

• Percentage of Participants With Clinically Significant Laboratory Values

  Baseline to the end of the study (Up to 312 Days)

• Percentage of Participants With Clinically Significant Vital Signs

  Baseline to the end of the study (Up to 312 days)

• Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2

  Cycle 1 Day 1 Pre-dose and, and at multiple timepoints (up to 168 hours) post-dose

Study Arms (3)

Alisertib: Normal Hepatic Function

EXPERIMENTAL

Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 50 mg, orally, twice daily (BID) for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 50 mg, BID for 7 days, followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Normal hepatic function includes participants with total bilirubin ≤ upper limit of the normal range \[ULN\] and alanine aminotransferase \[ALT\] level ≤ ULN.

Drug: Alisertib

Alisertib: Moderate Hepatic Impairment

EXPERIMENTAL

Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by alisertib 30 mg, BID for 7 days (Cycle 1 Day 8 to 14), followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 30 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Moderate hepatic impairment includes participants with total bilirubin \> 1.5-3 x ULN and any ALT level.

Drug: Alisertib

Alisertib: Severe Hepatic Impairment

EXPERIMENTAL

Alisertib 50 mg, orally, once, on Cycle 1 Day 1, followed by, alisertib 20 mg, BID for 7 days (Cycle 1 Day 8 to 14) followed by a 14-day rest period. Starting at Cycle 2 Day 1, alisertib 20 mg, BID for 7 days followed by a 14-day rest period unless a dose reduction is indicated. Participants may continue to receive alisertib until they experience progressive disease or unacceptable alisertib-related toxicities for up to 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. Severe hepatic impairment includes participants with total bilirubin \> 3 x ULN and any ALT level.

Drug: Alisertib

Interventions

Alisertib DRUG

Alisertib will be supplied as enteric coated tablets.

Also known as: MLN8237

Alisertib: Moderate Hepatic Impairment; Alisertib: Normal Hepatic Function; Alisertib: Severe Hepatic Impairment

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 of age or older.
• Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which standard curative or life-prolonging treatment does not exist or is no longer effective or tolerable.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Female participants who:
• Are post-menopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception).
• Male participants, even if surgically sterilized (ie, status postvasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception).
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
• Suitable venous access for the study-required blood sampling, including pharmacokinetics.
• Ability to swallow tablets.
• Participants with biliary obstruction for which a stent had been placed are eligible provided that the stent has been in place for more than 14 days before the first dose of alisertib and liver function has stabilized.
• Recovered from the reversible effects of prior antineoplastic therapy (ie, ≤ Grade 1 toxicity or baseline).

You may not qualify if:

• Participants of North/East Asian ethnicity (ie, Japanese, Chinese, Korean) will be excluded.
• Recurrent nausea and/or vomiting within 14 days before the first dose of alisertib or known gastrointestinal (GI) abnormality or GI procedure that could interfere with or modify the oral absorption or tolerance of alisertib. Examples include, but are not limited to, disease-related bowel obstruction, pancreatic insufficiency, use of pancreatic enzymes, a gastric condition (such as severe reflux or active peptic ulcer disease) that requires chronic and uninterrupted use of proton pump inhibitors, partial gastrectomy, history of small intestine surgery, and celiac disease.
• Participants requiring treatment with clinically significant enzyme inducers, such as the enzyme-inducing anti-epileptic drugs phenytoin, carbamazepine, phenobarbital, oxcarbazepine, primidone, rifampin, rifabutin, rifapentine, or St. John's wort within 14 days before the first dose of alisertib or requiring the use of these medications during the study.
• A medical condition requiring use of pancreatic enzymes; daily, chronic, or regular use of proton pump inhibitors (PPIs); or histamine 2 (H2) receptor antagonists. Participants who intermittently use these medications, must meet the following criteria:
• No use of PPIs within 5 days before the first dose of alisertib.
• No use of H2 antagonist or pancreatic enzymes within 24 hours before the first dose of alisertib.
• Inadequate bone marrow or other organ function (excluding hepatic impairment per eligibility criteria).
• Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of alisertib.
• 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 anticancer therapy or any investigational products within 3 weeks before the first dose of study drug.
• Exposure to nitrosoureas or mitomycin C within 42 days before the first dose of study drug.
• Radiotherapy within 14 days before the first dose of study drug.
• Prior treatment with radiation therapy involving ≥ 25% of the hematopoietically active bone marrow within 42 days before the first dose of study drug.
• Major surgery within 14 days before the first dose of study drug.
• Serious infection within 14 days before the first dose of study drug. Participant must have recovered from infection before first dose.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (7)

Unknown Facility

Miami, Florida, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Ann Arbor, Michigan, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

MLN 8237

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 12, 2014
• Study Start: August 21, 2014
• Primary Completion: April 5, 2016
• Study Completion: July 18, 2016
• Last Updated: November 15, 2018
• Results First Posted: November 15, 2018

Record last verified: 2018-04

Locations

US (7)