A Phase 1 Study of LY2835219 In Participants With Advanced Cancer

Lilly

Status and phase: Completed; Phase 1

Conditions: Advanced Cancer

Treatments: Drug: Abemaciclib; Drug: Fulvestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT01394016

13199

I3Y-MC-JPBA (Other Identifier)

Details and patient eligibility

About

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

Enrollment: 225 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

225 participants in 1 patient group

Abemaciclib

Experimental group

Description:

Participants received oral Abemaciclib administered on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as appropriate on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. Participants belonging to different Parts received the study drug as specified below: Part A: 50 mg/100 mg/150 mg/225 mg every 24 hours (Q24H) or 75mg/100 mg/150 mg/200 mg/275 mg every 12 hours (Q12H). Parts B, C, D, and E: 150 mg/200 mg Q12H. Part F: 150 mg Q12H. Part G: 200 mg Q12H along with 500 mg Fulvestrant administered intramuscularly.

Treatment:

Drug: Fulvestrant

Drug: Abemaciclib