A Phase 1 Study of LY2835219 In Participants With Advanced Cancer

Advanced Cancer Clinical Trial

Official title:

A Phase 1 Study of a CDK 4/6 Dual Inhibitor in Participants With Advanced Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01394016
• Other study ID #: 13199
• Secondary ID: I3Y-MC-JPBA
• Status: Completed
• Phase: Phase 1
• Start date: December 7, 2009
• Est. completion date: April 12, 2022

Study information

• Verified date: February 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine a safe dose of LY2835219 to be given to participants with advanced cancer and to determine any side effects that may be associated with LY2835219 in this population. Efficacy measures will be used to assess the activity of LY2835219 in this population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: April 12, 2022
• Est. primary completion date: May 29, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• For all Parts (Dose escalation and expansion): The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy either after available standard therapies have ceased to provide clinical benefit (Parts A, B, C, D, E and F) or in combination with fulvestrant (Part G only)

• For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic

• For Dose Expansion (Parts B, C, D, E, F and G): The participant must have histological or cytological evidence of one of the following cancers:

• Part B: Non-small cell lung cancer of any subtype that is advanced and/or metastatic

• Part C: Glioblastoma multiforme that has progressed or recurred after radiotherapy and/or chemotherapy

• Part D: Breast cancer that is advanced and/or metastatic

• Part E: Melanoma that is advanced and/or metastatic

• Part F: Colorectal Cancer

• Part G: Breast Cancer that is not only advanced and/or metastatic but also hormone receptor positive

• As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma

• For Parts A and G: Have measurable or nonmeasurable disease

• For Parts B, C, D, E and F: Have measurable disease

• Have given written informed consent prior to any study-specific procedures

• Have adequate hematologic, hepatic, and renal function

• Have a performance status less than or equal to 1 for Dose Escalation (Part A) and less than or equal to 2 for Dose Confirmation (Parts B, C, D, E, F and G) on the Eastern Cooperative Oncology Group (ECOG) scale

• Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) with the exception of fulvestrant (for Part G only) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment related toxicity resolved to baseline) except for residual alopecia

• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug

• Females with child bearing potential must have a negative serum pregnancy test within 3 days of the first dose of study drug

• Have an estimated life expectancy of greater than or equal to 12 weeks

• Are able to swallow capsules

Exclusion Criteria:

• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively

• Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), sudden cardiac death or sudden cardiac arrest

• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel)

• For Dose Escalation (Part A): Have central nervous system (CNS) malignancy or metastasis

• For Dose Confirmation (Parts B, D, E, F and G): Have CNS metastasis that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids

• For Dose Confirmation (Part C): Have glioblastoma multiforme that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids

• Have an acute leukemia

• Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug

• Females who are pregnant or lactating

• Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus [HIV] antibodies, hepatitis B surface antigen [HBSAg], or hepatitis C antibodies) Screening is not required for enrollment

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

Drug:
• LY2835219
Administered orally, daily for 28-day cycles for two planned cycles. For Part G only in addition to LY2835219 as above, fulvestrant is administered as specified in the label. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
• Fulvestrant
Fulvestrant is administered intramuscularly into the buttocks as specified in the label in Part G only.

Locations

Country	Name	City	State
United States	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	Boston	Massachusetts
United States	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	San Antonio	Texas
United States	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.	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with clinically significant effects (physical assessments and safety lab tests)		Baseline through study completion (approximately 38 months)
Secondary	Number of participants with tumor response		Baseline through study completion (approximately 38 months)
Secondary	Pharmacokinetics, maximum plasma concentration (Cmax)		Days -3, -2, -1, Days 1, 15, 22, 28 and 29 of Cycle 1
Secondary	Pharmacokinetics, area under the curve (AUC)		Days -3, -2, -1, Days 1, 15, 22, 28 and 29 of Cycle 1
Secondary	Recommended dose for phase 2 studies		Baseline to study completion (approximately 38 months)