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Trial record 2 of 4 for:    LY2812176

Study of DKN-01 and Gemcitabine/Cisplatin in Patients With Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02375880
First received: February 18, 2015
Last updated: September 6, 2016
Last verified: September 2016
  Purpose
DKN-01 is a humanized monoclonal antibody (Mab) with neutralizing activity against Dkk-1 and is being developed as an anti-neoplastic agent. This study is designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of DKN-01 in combination with gemcitabine and cisplatin in patients with carcinoma primary to the intra- or exta-hepatic biliary system or gallbladder.

Condition Intervention Phase
Carcinoma of Intrahepatic and Extra-hepatic Biliary System
Carcinoma of Gallbladder
Bile Duct Cancer
Cholangiocarcinoma
Drug: DKN-01
Drug: gemcitabine
Drug: cisplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation and Cohort Expansion Study of DKN-01 in Combination With Gemcitabine and Cisplatin in Patients With Advanced Carcinoma Primary to the Intra- or Extra-hepatic Biliary System or Gallbladder

Resource links provided by NLM:


Further study details as provided by Leap Therapeutics, Inc.:

Primary Outcome Measures:
  • Maximum tolerated dose and dose-limiting toxicities as determined in Part A. [ Time Frame: End of Cycle 1 (Day 21) ] [ Designated as safety issue: Yes ]
    Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03).

  • Composite Safety parameters as assessed by new or changing physical examinations, vital signs, electrocardiograms (ECGs), clinical laboratories, concomitant medication reviews, and assessment of adverse events. [ Time Frame: Parts A and B: at a minimum Days 1, 8, 15 of each treatment cycle. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics - AUC [ Time Frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1 ] [ Designated as safety issue: No ]
    Plasma levels will be measured during the treatment period.

  • Pharmacokinetics - Cmax [ Time Frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1 ] [ Designated as safety issue: No ]
    Plasma levels will be measured during the treatment period.

  • Pharmacokinetics - Tmax [ Time Frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1 ] [ Designated as safety issue: No ]
    Plasma levels will be measured during the treatment period.

  • Efficacy - Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1) [ Time Frame: At baseline, prior to the start of Cycle 3, and every 2 cycles thereafter until disease progression or death ] [ Designated as safety issue: No ]
    Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1).


Enrollment: 27
Study Start Date: June 2015
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 150 mg DKN-01 Part A
Patients will receive 150 mg of DKN-01 followed by gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle.
Drug: DKN-01
Administration by intravenous (IV) infusion.
Other Name: LY2812176
Drug: gemcitabine
Administered by IV infusion.
Other Name: Gemzar
Drug: cisplatin
Administered by IV infusion
Other Name: Platinol
Experimental: 300 mg DKN-01 Part A
Patients will receive 300 mg of DKN-01 followed by gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle.
Drug: DKN-01
Administration by intravenous (IV) infusion.
Other Name: LY2812176
Drug: gemcitabine
Administered by IV infusion.
Other Name: Gemzar
Drug: cisplatin
Administered by IV infusion
Other Name: Platinol
Experimental: MTD mg DKN-01 Part B
Patients are treated at the maximum tolerated dose (MTD) of DKN-01 (or highest dose tested in Part A if the MTD is not defined) followed by gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on Days 1 and 8 of each 21-day cycle.
Drug: DKN-01
Administration by intravenous (IV) infusion.
Other Name: LY2812176
Drug: gemcitabine
Administered by IV infusion.
Other Name: Gemzar
Drug: cisplatin
Administered by IV infusion
Other Name: Platinol

Detailed Description:

In Part A, escalating doses of DKN-01 will be administered to different cohorts of patients to evaluate safety and dose limiting toxicities (DLTs) and to establish the maximum tolerated dose of DKN-01 when administered in combination with gemcitabine and cisplatin.

Part B is an expansion cohort in which patients are treated at the MTD of DKN-01 (or highest dose tested if the MTD is not defined) to further characterize safety, tolerability, pharmacokinetics and efficacy within the defined patient population.

  Eligibility

Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient has carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder.
  2. Patient must have sufficient tumor tissue available for submission.
  3. For patients who have received prior cryotherapy, radiofrequency ablation, radioembolization, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, at least 28 days must have elapsed since that therapy, and lesions that have not been treated with local therapy must be present and measurable.
  4. Patients may have received prior adjuvant chemotherapy with gemcitabine with or without cisplatin, as long as 6 months have elapsed since last treatment.
  5. Patients must have one or more tumors measurable on radiographic imaging as defined by RECIST.
  6. ECOG PS of 0 or 1. Patients with an ECOG PS of 2 may be entered upon review and approval of the medical monitor.
  7. Estimated life expectancy of at least 3 months.
  8. Disease-free of active second/secondary or prior malignancies for ≥ 2 years with the exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast.
  9. Adequate hematological, renal, hepatic and coagulation laboratory test results.
  10. Women of child bearing potential and men must agree to use adequate contraception during the study and for 6 months after their last dose of study drug.
  11. Available for the duration of the study and are willing to follow study-specific procedures.
  12. Provide written informed consent

Exclusion Criteria:

  1. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
  2. Have Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 (male), or history of congenital long QT syndrome.
  3. Active, uncontrolled bacterial, viral, or fungal infections.
  4. Known to be human immunodeficiency virus (HIV) positive or has untreated, active hepatitis B.
  5. History of major organ transplant.
  6. History of an autologous/allogenic bone marrow transplant.
  7. Serious nonmalignant disease.
  8. Pregnant or nursing.
  9. History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are symptomatic and clinically significant.
  10. Symptomatic central nervous system (CNS) malignancy or metastasis.
  11. Clinically significant peripheral neuropathy
  12. Known osteoblastic bony metastasis.
  13. Treatment with surgery or chemotherapy within 21 days prior to study entry or radiation within 14 days of study entry.
  14. Previously treated with an anti-Dkk-1 therapy.
  15. Other exclusions apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02375880

Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90033
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
University Hospitals, Case Medical Center
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Leap Therapeutics, Inc.
  More Information

Responsible Party: Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02375880     History of Changes
Other Study ID Numbers: DEK-DKK1-P103 
Study First Received: February 18, 2015
Last Updated: September 6, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Bile Duct Neoplasms
Cholangiocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Adenocarcinoma
Gemcitabine
Cisplatin
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

ClinicalTrials.gov processed this record on December 02, 2016