A Study in Patients With Advanced or Metastatic Cancer

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

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

Study Overview

• Status: Completed
• Conditions: Metastases, Neoplasm
• Intervention / Treatment: Drug: LY2780301

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • 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, 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2780301; Part A: daily dosing Part B (if determined as needed by pharmacokinetic, pharmacodynamic, and safety data): twice daily dosing Part C: Dose and frequency as determined by Parts A and B of the study.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recommended dose for Phase 2 Studies	Baseline to study completion

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinically significant effects	Baseline to study completion
Pharmacokinetics, area under the concentration-time curve	Baseline, Days 1, 2, 8, 15, and 22 of Cycle 1, Day 1 of Cycle 2
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.
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.
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.
Pharmacokinetics, maximum concentration (Cmax)	Baseline, Days 1, 2, 8, 15, and 22 of Cycle 1, Day 1 of Cycle 2

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: April 22, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): July 31, 2012
• Last Update Submitted That Met QC Criteria: July 30, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Advanced Cancer; Metastatic Cancer; Solid Tumors
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 13127; I4H-MC-JWAA (Other Identifier: Eli Lilly and Company)