A Study of Enzastaurin in Chinese Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01432951
First received: September 9, 2011
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Solid Tumor
Lymphoma, Malignant
Drug: Enzastaurin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Pharmacokinetics of Enzastaurin HCl in Native Chinese Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics: area under the concentration-time curve over a dosing interval at steady state (AUCt,ss) of enzastaurin, its principle metabolites and total analyte [ Time Frame: Day 14 dose: Predose and up to 96 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: maximum observed drug concentration (Cmax) at steady state of enzastaurin, its principle metabolites and total analyte [ Time Frame: Day 14 dose: Predose and up to 96 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: time of maximal plasma concentration (tmax) of enzastaurin, its principle metabolites and total analyte [ Time Frame: Day 14 dose: Predose and up to 96 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: average concentration during a dosing interval at steady state (Cav,ss) of enzastaurin, its principle metabolites and total analyte [ Time Frame: Day 14 dose: Predose and up to 96 hours post dose ] [ Designated as safety issue: No ]
  • Pharmacokinetics: terminal elimination half-life of enzastaurin and its principle metabolites [ Time Frame: Day 14 dose: Predose and up to 96 hours post dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: November 2011
Estimated Study Completion Date: March 2015
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzastaurin

Pharmacokinetic Phase: Enzastaurin 500 mg, four 125-mg tablets administered orally once daily for 14 days. Dosing is held for 3 days, and resumes on Day 18. Patients may be allowed to receive enzastaurin for an additional (approximately) 2 to 4 weeks.

Safety Extension: Patients are allowed to continue receiving enzastaurin until disease progression or discontinuation criteria are met, as per the investigator's assessment.

Drug: Enzastaurin
Administered orally
Other Name: LY317615

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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: patients with glioblastoma, and other hematologic malignancies [except lymphoma] are excluded from this study.)
  • Male and female patients 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 patients have hormone-refractory prostate cancer, the study doctor will discuss with the patients 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/L prior to treatment, platelets greater than or equal to 100 × 10^9/L, and hemoglobin greater than or equal to 10 g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Patients 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 mg/dL
  • Electrolytes: Patients may be entered into the study if, in the investigator's opinion, any electrolyte disorders, including potassium less than 3.4 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 patient will be discontinued from the study. Patients with hypercalcemia are excluded.
  • Have an estimated life expectancy, in the judgment of the investigator, that will permit the patient to complete the PK phase and at least 1 cycle of the safety extension phase (if the patient 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
  • Patients with glioblastoma or hematologic malignancies other than lymphoma are excluded from this study. Patients who have central nervous system (CNS) metastases (unless the patient 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 mL of beer; 5 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432951

Locations
China
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.
Beijing, China, 100071
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.
Changsha, China, 410013
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.
Guang Zhou, China, 510060
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01432951     History of Changes
Other Study ID Numbers: 13322, H6Q-FW-JCCC
Study First Received: September 9, 2011
Last Updated: August 25, 2014
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014