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

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ClinicalTrials.gov Identifier: NCT02784795
Recruitment Status : Active, not recruiting
First Posted : May 27, 2016
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumor Breast Cancer Colon Cancer Cholangiocarcinoma Soft Tissue Sarcoma Drug: LY3039478 Drug: Taladegib Drug: Abemaciclib Drug: Cisplatin Drug: Gemcitabine Drug: Carboplatin Drug: LY3023414 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 163 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors
Actual Study Start Date : November 4, 2016
Actual Primary Completion Date : August 9, 2018
Estimated Study Completion Date : January 31, 2019


Arm Intervention/treatment
Experimental: LY3039478 + Taladegib
LY3039478 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.
Drug: LY3039478
Administered orally

Drug: Taladegib
Administered orally
Other Name: LY2940680

Experimental: LY3039478 + LY3023414
LY3039478 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.
Drug: LY3039478
Administered orally

Drug: LY3023414
Administered orally

Experimental: LY3039478 + Abemaciclib
LY3039478 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.
Drug: LY3039478
Administered orally

Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Experimental: LY3039478 + Cisplatin/Gemcitabine
LY3039478 given orally TIW in combination with cisplatin and gemcitabine given as intravenous (IV) infusions on days 1 and 8 of a 21 day cycle.
Drug: LY3039478
Administered orally

Drug: Cisplatin
Administered IV

Drug: Gemcitabine
Administered IV

Experimental: LY3039478 + Gemcitabine/Carboplatin
LY3039478 given orally TIW in combination with gemcitabine and carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.
Drug: LY3039478
Administered orally

Drug: Gemcitabine
Administered IV

Drug: Carboplatin
Administered IV




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of LY3039478 [ Time Frame: Cycle 1 (up to 28 Days) ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Disease Progression or Death (Estimated up to 12 Months) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02784795


Locations
United States, Florida
Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Denmark
Rigshospitalet
Copenhagen, København Ø, Denmark, 2100
France
Institut Bergonie
Bordeaux, France, 33076
Centre Leon Berard
Lyon Cedex 08, France, 69373
Gustave Roussy
Villejuif Cedex, France, 94805
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Fundacion Jimenez Diaz
Madrid, Spain, 28040
Hospital Madrid Norte Sanchinarro
Madrid, Spain, 28050
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company

Additional Information:
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02784795     History of Changes
Other Study ID Numbers: 16209
I6F-MC-JJCD ( Other Identifier: Eli Lilly and Company )
2015-004421-14 ( EudraCT Number )
First Posted: May 27, 2016    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 1, 2018

Keywords provided by Eli Lilly and Company:
Notch Inhibitor

Additional relevant MeSH terms:
Cholangiocarcinoma
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Gemcitabine
Cisplatin
Carboplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs