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

Principal Investigator

Breelyn Wilky

Clinical Trial ID

Institutional Protocol # 20140634
National Clinical Trials Identifier NCT02214147

Clinical Trial Summary


Phase

Phase 1


Funding Agency/Sponsor

Industrial


Disease

Leukemia, Lymphoma, and Myeloma


Enrollment Eligibility

Inclusion Criteria:
1. Male or female participants 18 years of age or older.
2. 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.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
4. 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).
5. 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).
6. 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be withdrawn by the participant at any time without prejudice to future medical care.
7. Suitable venous access for the study-required blood sampling, including
pharmacokinetics.
8. Ability to swallow tablets.
9. 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.
10. Recovered from the reversible effects of prior antineoplastic therapy (ie, ≤ Grade 1
toxicity or baseline).
11. Clinical laboratory values as specified below:
- Absolute neutrophil count (ANC) ≥ 1500/μL and platelet count ≥ 75,000/μL.
- Participants with normal hepatic function: Total bilirubin and alanine
aminotransferase (ALT) must be ≤ upper limit of the normal range (ULN).
- Participants with moderate hepatic impairment: total bilirubin must be > 1.5
to 3 x ULN with any ALT level.
- Participants with severe hepatic impairment: total bilirubin must be > 3 x
ULN with any ALT level.
- Measured creatinine clearance or calculated creatinine clearance > 30
mL/minute. Note: If a calculated creatinine clearance is used, it should be
calculated according to the Cockcroft-Gault formula.
- Hemoglobin must be ≥ 8 g/dL.
Exclusion Criteria:
1. Participants of North/East Asian ethnicity (ie, Japanese, Chinese, Korean) will be
excluded.
2. 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.
3. 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.
4. 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.
5. Inadequate bone marrow or other organ function (excluding hepatic impairment per
eligibility criteria).
6. 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.
7. Any serious medical or psychiatric illness that could, in the investigator's opinion,
potentially interfere with the completion of treatment according to this protocol.
8. Treatment with any anticancer therapy or any investigational products within 3 weeks
before the first dose of study drug.
9. Exposure to nitrosoureas or mitomycin C within 42 days before the first dose of study
drug.
10. Radiotherapy within 14 days before the first dose of study drug.
11. Prior treatment with radiation therapy involving ≥ 25% of the hematopoietically active
bone marrow within 42 days before the first dose of study drug.
12. Major surgery within 14 days before the first dose of study drug.
13. Serious infection within 14 days before the first dose of study drug. Participant must
have recovered from infection before first dose.
14. Life-threatening illness unrelated to cancer.
15. Symptomatic brain metastasis. Participants with brain metastases:
- Must have stable neurologic status following local therapy (surgery or radiation)
for at least 2 weeks after completion of the definitive therapy AND
- Must be without neurologic dysfunction that would confound the evaluation of
neurologic or other adverse events (AEs).
16. Clinically significant coagulopathy or bleeding disorder.
17. Severe central nervous system, pulmonary, or renal disease not related to the
participant's cancer.
18. Known human immunodeficiency virus (HIV) positive.
19. Known history of hepatitis C infection or suspected currently active hepatitis C
infection, or known or suspected history of hepatitis B infection. Participants with
known or suspected history of hepatitis B infection were to be screened and excluded
when any of the following conditions were met:
- Received hematopoietic stem cell transplantation (either allogeneic or
autologous), or
- Received any rituximab-containing treatment regimen in the last 12 months before
entering the study, or
- Tested positive for the presence of at least 1 of the following 3 markers in
blood (evaluated at Screening): hepatitis B surface antigen (HBsAg), antibodies
against hepatitis B core antigen (anti-HBc), or hepatitis B virus
deoxyribonucleic acid (HBV DNA).
20. Any of the following cardiovascular conditions:
- Evidence of current uncontrolled cardiovascular conditions, including cardiac
arrhythmias, congestive heart failure, angina, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities.
- Corrected QT interval (QTc) > 500 milliseconds in a 12-lead electrocardiogram
(ECG) during screening.
21. History of uncontrolled sleep apnea syndrome or other condition that could result in
excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
22. Use of moderate or strong cytochrome P450 (CYP) 3A inhibitors or CYP3A inducers within
2 weeks before the first dose of study drug.


Contact Information

Phone Number 305-243-2647
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