Clinical Trials /

A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors

NCT02784795

Description:

The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with other anticancer agents in participants with advanced or metastatic solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Cholangiocarcinoma
  • Colon Carcinoma
  • Lymphoma
  • Malignant Solid Tumor
  • Soft Tissue Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 16209
  • SECONDARY ID: I6F-MC-JJCD
  • SECONDARY ID: 2015-004421-14
  • NCT ID: NCT02784795

Conditions

  • Solid Tumor
  • Breast Cancer
  • Colon Cancer
  • Cholangiocarcinoma
  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
LY3039478LY3039478 + Taladegib
TaladegibLY2940680LY3039478 + Taladegib
AbemaciclibLY2835219LY3039478 + Abemaciclib
CisplatinLY3039478 + Cisplatin/Gemcitabine
GemcitabineLY3039478 + Cisplatin/Gemcitabine
CarboplatinLY3039478 + Gemcitabine/Carboplatin
LY3023414LY3039478 + LY3023414

Purpose

The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with other anticancer agents in participants with advanced or metastatic solid tumors.

Trial Arms

NameTypeDescriptionInterventions
LY3039478 + TaladegibExperimentalLY3039478 given orally 3 times per week (TIW) in combination with taladegib given orally daily on a 28 day cycle. A single dose of taladegib will also be given on day 1 during a 3-day lead-in period.
  • LY3039478
  • Taladegib
LY3039478 + LY3023414ExperimentalLY3039478 given orally TIW in combination with LY3023414 given orally every 12 hours on a 28-day cycle. A single dose of LY3023414 will also be given on day 1 during a 3-day lead-in period.
  • LY3039478
  • LY3023414
LY3039478 + AbemaciclibExperimentalLY3039478 given orally TIW in combination with abemaciclib given orally every 12 hours on a 28-day cycle. A single dose of abemaciclib will also be given on day 1 during a 3-day lead-in period.
  • LY3039478
  • Abemaciclib
LY3039478 + Cisplatin/GemcitabineExperimentalLY3039478 given orally TIW in combination with cisplatin and gemcitabine given as intravenous (IV) infusions on days 1 and 8 of a 21 day cycle.
  • LY3039478
  • Cisplatin
  • Gemcitabine
LY3039478 + Gemcitabine/CarboplatinExperimentalLY3039478 given orally TIW in combination with gemcitabine and carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.
  • LY3039478
  • Gemcitabine
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  For all parts: The participant 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 advanced or metastatic cancer.

               -  For dose escalation for all combinations: The participant must have histological
                  or cytological evidence of cancer, either a solid tumor or a lymphoma, which is
                  advanced or metastatic.

               -  For Part A dose confirmation: All participants must have histological evidence of
                  advanced or metastatic soft tissue sarcoma or breast cancer. Breast cancer
                  participants must have prescreened mutations, amplification, or gene/protein
                  expression alterations related to Notch pathway.

               -  For Part B dose confirmation: All participants must have histological evidence of
                  advanced or metastatic colon cancer or soft tissue sarcoma. Colon cancer
                  participants must have prescreened mutations, amplification, or gene/protein
                  expression alterations related to Notch pathway.

               -  For Part C dose confirmation: All participants must have histological evidence of
                  advanced or metastatic breast cancer and prescreened mutations, amplification, or
                  gene/protein expression alterations related to Notch pathway.

               -  For Part D dose confirmation: All participants must have histological evidence of
                  cholangiocarcinoma and prescreened mutations, amplification, or gene/protein
                  expression alterations related to Notch pathway. Participants must not have
                  received >1 line of prior systemic therapy for metastatic or resectable disease
                  (that is, participants may have received adjuvant gemcitabine and then later
                  gemcitabine/cisplatin for recurrent metastatic disease).

               -  For Part E dose confirmation: All participants must have histological evidence of
                  locally advanced or metastatic triple negative breast cancer (TNBC) and
                  prescreened mutations, amplification, or gene/protein expression alterations
                  related to Notch pathway. Participants must not have received >2 lines of
                  systemic treatment for advanced or metastatic TNBC.

          -  Have adequate organ function.

          -  Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG)
             scale.

          -  Have discontinued all previous therapies for cancer.

        Exclusion Criteria:

          -  Have current acute leukemia.

          -  Have current or recent (within 3 months of study drug administration) gastrointestinal
             disease with chronic or intermittent diarrhea, or disorders that increase the risk of
             diarrhea, such as inflammatory bowel disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of LY3039478
Time Frame:Cycle 1 (up to 28 Days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve (AUC) of LY3039478 in Combination with Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin
Time Frame:Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Safety Issue:
Description:
Measure:PK: AUC of Taladegib and its Active Metabolite LSN3185556, in Combination with LY3039478
Time Frame:Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Safety Issue:
Description:
Measure:PK: AUC of LY3023414 in Combination with LY3039478
Time Frame:Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Safety Issue:
Description:
Measure:PK: AUC of Abemaciclib and its Major Active Metabolites LSN2839567 and LSN3106726, in Combination with LY3039478
Time Frame:Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Safety Issue:
Description:
Measure:Duration of Response (DoR)
Time Frame:Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Estimated up to 12 Months)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Baseline to Objective Disease Progression or Death (Estimated up to 12 Months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • Notch Inhibitor

Last Updated

July 17, 2017