Clinical trial NCT01432951: A Study of Enzastaurin in Chinese Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma
Official title: Pharmacokinetics of Enzastaurin HCl in Native Chinese Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lymphoma, Malignant
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-09-13
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess the pharmacokinetics (PK) of enzastaurin and its metabolites in native Chinese participants with advanced and/or metastatic solid tumors or lymphoma. Information about any side effects that may occur will also be collected. Treatment of disease is not the main purpose of the study.

This is a Phase 1 study of enzastaurin in native Chinese participants with advanced and/or metastatic solid tumors or lymphoma. Participants will receive daily doses of enzastaurin for 14 days, stop dosing for 3 days during PK sampling, and resume dosing on Day 18. Participants may be allowed to receive enzastaurin for approximately 2 to 4 weeks after day 18 to provide an opportunity for a participant's oncologist to assess the potential benefit of the participant continuing to receive enzastaurin in the safety extension phase. There is no planned duration for the extension phase; participants are allowed to continue receiving enzastaurin until disease progression or other reason for discontinuation as per the investigator's assessment.


Eligibility criteria: Inclusion Criteria:

* Have given written informed consent
* Have a histologic or cytologic diagnosis of cancer (solid tumor or lymphoma) with clinical or radiologic evidence of locally advanced and/or metastatic disease for which no life-prolonging therapy exists. (Note: participants with glioblastoma, and other hematologic malignancies \[except lymphoma\] are excluded from this study.)
* Male and female participants with reproductive potential must use an approved contraceptive method, if appropriate (for example, intrauterine device, birth control pills, or barrier device) during and for 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
* Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale and, in the investigator's opinion, are suitable for participation in the study
* Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, anticancer hormone therapy, or other investigational therapy for at least 30 days prior to study entry (6 weeks for mitomycin-C or nitrosoureas), and have recovered from the acute effects of therapy
* If the participants have hormone-refractory prostate cancer, the study doctor will discuss with the participants what drugs they would be allowed to continue to receive during the study
* Have adequate organ function, including:

  * Bone Marrow Reserve: absolute neutrophil count (ANC) greater than or equal to 1.5 × 10\^9/Liter (L) prior to treatment, platelets greater than or equal to 100 × 10\^9/L, and hemoglobin greater than or equal to 10 gram/deciliter (g/dL). Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Participants may be allowed erythropoietin of choice as per standard of care.
  * Hepatic: bilirubin within 1.5 times the upper limit of normal (ULN), alanine transaminase, and aspartate transaminase less than or equal to 2.5 times ULN or less than or equal to 5 times ULN when liver metastases are known
  * Renal: serum creatinine less than or equal to 1.5 milligram/deciliter (mg/dL)
* Electrolytes: Participants may be entered into the study if, in the investigator's opinion, any electrolyte disorders, including potassium less than 3.4 milliequivalents/liter (mEq/L), calcium less than 8.4 mg/dL, or magnesium less than 1.2 (mEq/L), may be appropriately managed and stabilized by the time of the laboratory evaluation on the lead-in day. If electrolytes have not been stabilized during this time, the participant will be discontinued from the study. Participants with hypercalcemia are excluded.
* Have an estimated life expectancy, in the judgment of the investigator, that will permit the participant to complete the PK phase and at least 1 cycle of the safety extension phase (if the participant were to participate in the safety extension phase)

Exclusion Criteria:

* Have received treatment within 28 days of the first dose of study drug with an experimental agent for non cancer indications that has not received regulatory approval for any indication
* Participants with glioblastoma or hematologic malignancies other than lymphoma are excluded from this study. Participants who have central nervous system (CNS) metastases (unless the participant has completed successful local therapy.

for CNS metastases and has been off of corticosteroids for at least 4 weeks before starting study therapy) are excluded. In the absence of a clinical suspicion of brain metastases, no screening computed tomography (CT) or magnetic resonance imaging (MRI) scan before enrollment is required.

* Serious concomitant systemic disorder, including active infection, that is incompatible with the study (at the discretion of the investigator)
* Have a history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infections
* Have a serious cardiac condition
* Have abnormal electrocardiogram (ECG) findings, at the discretion of the investigator
* Use medications that are known to cause certain changes in electrocardiogram (ECG) readings
* Have a history of unexplained syncope (fainting or passing out) within the last year, or have a known family history of unexplained sudden death
* Have had a complete gastrectomy or other significant gastrointestinal diseases that, in the investigator's opinion, may significantly impact drug absorption
* Are receiving total parenteral nutrition
* Are not able to swallow tablets
* Are a woman who is breast feeding, lactating, or pregnant
* Are allergic to enzastaurin
* Are receiving herbal regimens
* Drugs and herbal supplements that are known to be potent or moderate inhibitors or inducers of cytochrome P450 (CYP)3A are specifically excluded. Foods that are known to be potent or moderate inhibitors of CYP3A (for example, grapefruit, grapefruit juice, Seville oranges, or Seville orange juice) are also specifically excluded during the study. In addition, starfruit and starfruit juice are excluded during the PK phase of the study.
* Drugs with narrow therapeutic windows that are also known substrates of CYP2C9, CYP2C8, CYP2C19, and CYP3A are excluded
* Have an average weekly alcohol intake that exceeds 21 units per week (men) and 14 units per week (women) or are unwilling to stop alcohol consumption from the lead-in day through the completion of collecting samples for study drug measurement (1 unit = 12 oz or 360 milliliter (mL) of beer; 5 ounces (oz) or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
* Use of drugs of abuse, as evidenced by history and/or positive findings on urinary drug screening, unless prescribed by a physician (for example, narcotic pain medication)
* The investigator thinks you should not participate for any reason

Primary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration -Time Curve Over a Dosing Interval at Steady State (AUCt,ss) of Enzastaurin, It's Metabolites and Total Analytes in Plasma
timeFrame: Day 14: Predose and 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours post dose
measure: PK: Maximum Observed Drug Concentration at Steady State (Cmax,ss) of Enzastaurin, It's Metabolites and Total Analytes in Plasma
timeFrame: Day 14: Predose and and 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours post dose
measure: PK: Time of Maximal Plasma Concentration at Steady State (Tmax, ss) of Enzastaurin, It's Metabolites and Total Analytes in Plasma
timeFrame: Day 14: Predose and 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours post dose
measure: PK: Average Concentration During a Dosing Interval at Steady State (Cav,ss) of Enzastaurin, It's Metabolites and Total Analytes in Plasma
timeFrame: Day 14: Predose and and 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours post dose
measure: PK: Terminal Elimination Half-Life of Enzastaurin, It's Metabolites and Total Analytes in Plasma
timeFrame: Day 14: Predose and 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours post dose
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Changsha
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Guang Zhou
country: China
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Li X, Fang X, Li S, Zhang W, Yang N, Cui Y, Huang H, Cai R, Lin X, Fu X, Hong H, Lin T. A pharmacokinetic and safety study of a fixed oral dose of enzastaurin HCl in native Chinese patients with refractory solid tumors and lymphoma. Oncotarget. 2016 Apr 5;7(14):18585-93. doi: 10.18632/oncotarget.7875.