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Trial record 6 of 8 for:    DKN-01

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

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ClinicalTrials.gov Identifier: NCT02375880
Recruitment Status : Completed
First Posted : March 3, 2015
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
Leap Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE February 18, 2015
First Posted Date  ICMJE March 3, 2015
Last Update Posted Date September 10, 2018
Study Start Date  ICMJE June 2015
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2015)
  • Maximum tolerated dose and dose-limiting toxicities as determined in Part A. [ Time Frame: End of Cycle 1 (Day 21) ]
    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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02375880 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2015)
  • Pharmacokinetics - AUC [ Time Frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1 ]
    Plasma levels will be measured during the treatment period.
  • Pharmacokinetics - Cmax [ Time Frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1 ]
    Plasma levels will be measured during the treatment period.
  • Pharmacokinetics - Tmax [ Time Frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1 ]
    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 ]
    Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of DKN-01 and Gemcitabine/Cisplatin in Patients With Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma of Intrahepatic and Extra-hepatic Biliary System
  • Carcinoma of Gallbladder
  • Bile Duct Cancer
  • Cholangiocarcinoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: DKN-01
    • Drug: gemcitabine
    • Drug: cisplatin
  • 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.
    Interventions:
    • Drug: DKN-01
    • Drug: gemcitabine
    • Drug: cisplatin
  • 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.
    Interventions:
    • Drug: DKN-01
    • Drug: gemcitabine
    • Drug: cisplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 8, 2017)
51
Original Estimated Enrollment  ICMJE
 (submitted: February 25, 2015)
32
Actual Study Completion Date  ICMJE July 2018
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02375880
Other Study ID Numbers  ICMJE DEK-DKK1-P103
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Leap Therapeutics, Inc.
Study Sponsor  ICMJE Leap Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Leap Therapeutics, Inc.
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP