A Study in Patients With Advanced or Metastatic Cancer

Metastases, Neoplasm Clinical Trial

Official title:

A Phase I Trial of Single-Agent LY2780301 in Patients With Advanced or Metastatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01115751
• Other study ID #: 13127
• Secondary ID: I4H-MC-JWAA
• Status: Completed
• Phase: Phase 1
• First received: April 22, 2010
• Last updated: July 30, 2012
• Start date: March 2010
• Est. completion date: July 2012

Study information

• Verified date: July 2012
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

Study JWAA is a multicenter, nonrandomized, open-label, dose-escalation Phase 1 study of oral LY2780301 in patients with advanced solid tumors.

Description:

JWAA will consist of the following treatment phases parts:

Part A - Dose escalation phase using a once-daily dosing schedule. Part B - Dose escalation phase using a twice-daily dosing schedule. Part C - Dose expansion phase using the maximum tolerated dose from either Part A or Part B.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic (including Non-Hodgkin's Lymphoma). The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their disease.

• Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma.

Parts A and B: have measurable or nonmeasurable disease. Part C: have measurable disease.

• Have adequate organ function, including:

• Hematologic: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, platelets greater than or equal to 100 x 109/L, and hemoglobin greater than or equal to 8 g/dL. Transfusions are not allowed to reach 8 g/dL prior to enrollment.

• Hepatic: Bilirubin less than or equal to 1.5 times upper limits of normal (ULN), alanine aminotransaminase (ALT), and aspartate aminotransaminase (AST) less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST and ALT equaling less than or equal to 5 times ULN are acceptable.

• Renal: Serum creatinine less than or equal to 1.5 times ULN or calculated creatinine clearance greater than 45 ml/mn.

• Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

• Have discontinued previous treatments for cancer and recovered from the acute effects of therapy: at least 28 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents. At the discretion of the investigator, hormone-refractory prostate cancer patients who are stable on gonadotropin-releasing hormone (GnRH) agonist therapy may have that treatment continued while they are enrolled in this study.

Exclusion Criteria:

• Have received treatment within 28 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication.

• Have serious preexisting medical conditions (left to the discretion of the investigator).

• Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days.

• Have current acute or chronic leukemia.

• Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).

• Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results.

• Have QTc interval of >470 msec on screening electrocardiogram(ECG).

• Treatment with a strong CYP3A4 substrate with narrow therapeutic range, strong inhibitor, or inducer.

• Have history of pituitary adenoma.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastases, Neoplasm
• Neoplasm Metastasis

Intervention

Drug:
• LY2780301
Administered orally, daily for two 28-day cycles. Starting dose is 100mg. The dose will be subsequently increased to 200mg, 300mg, 400mg, 500mg, and 600mg if no dose limiting toxicity is observed at the prior dose levels. Patients who, in the opinion of the investigator, demonstrate clinical benefit may receive treatment beyond two cycles until disease progression.

Locations

Country	Name	City	State
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Barcelona
Spain	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended dose for Phase 2 Studies		Baseline to study completion	Yes
Secondary	Clinically significant effects		Baseline to study completion	Yes
Secondary	Pharmacokinetics, area under the concentration-time curve		Baseline, Days 1, 2, 8, 15, and 22 of Cycle 1, Day 1 of Cycle 2	No
Secondary	Best overall response (CR+PR+SD)		Baseline to measured disease progression. Tumor assessments are performed every 2 cycles until disease progression and during post-study follow-up period.	No
Secondary	Progression-free survival		Baseline to measured disease progression or death. Tumor assessments are performed every 2 cycles until disease progression and during post-study follow-up period.	No
Secondary	Duration of response		Time of response to disease progression or death. Tumor assessments are performed every 2 cycles until disease progression and during post-study follow-up period.	No
Secondary	Pharmacokinetics, maximum concentration (Cmax)		Baseline, Days 1, 2, 8, 15, and 22 of Cycle 1, Day 1 of Cycle 2	No