Study of DKN-01 and Gemcitabine/Cisplatin in Patients With Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder
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
1 other identifier
interventional
51
1 country
9
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2015
Typical duration for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 18, 2015
CompletedFirst Posted
Study publicly available on registry
March 3, 2015
CompletedStudy Start
First participant enrolled
June 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2018
CompletedAugust 3, 2025
July 1, 2025
3.1 years
February 18, 2015
July 30, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose and dose-limiting toxicities as determined in Part A.
Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.03).
End of Cycle 1 (Day 21)
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.
Parts A and B: at a minimum Days 1, 8, 15 of each treatment cycle.
Secondary Outcomes (4)
Pharmacokinetics - AUC
Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Pharmacokinetics - Cmax
Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Pharmacokinetics - Tmax
Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Efficacy - Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1)
At baseline, prior to the start of Cycle 3, and every 2 cycles thereafter until disease progression or death
Study Arms (3)
150 mg DKN-01 Part A
EXPERIMENTALPatients 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.
300 mg DKN-01 Part A
EXPERIMENTALPatients 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.
MTD mg DKN-01 Part B
EXPERIMENTALPatients 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
Administration by intravenous (IV) infusion.
Administered by IV infusion.
Administered by IV infusion
Eligibility Criteria
You may qualify if:
- Patient has carcinoma primary to the intra- or extra-hepatic biliary system or gall bladder.
- Patient must have sufficient tumor tissue available for submission.
- 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.
- Patients may have received prior adjuvant chemotherapy with gemcitabine with or without cisplatin, as long as 6 months have elapsed since last treatment.
- Patients must have one or more tumors measurable on radiographic imaging as defined by RECIST.
- ECOG PS of 0 or 1. Patients with an ECOG PS of 2 may be entered upon review and approval of the medical monitor.
- Estimated life expectancy of at least 3 months.
- 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.
- Adequate hematological, renal, hepatic and coagulation laboratory test results.
- 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.
- Available for the duration of the study and are willing to follow study-specific procedures.
- Provide written informed consent
You may not qualify if:
- New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
- Have Fridericia-corrected QT interval (QTcF) \> 470 msec (female) or \> 450 (male), or history of congenital long QT syndrome.
- Active, uncontrolled bacterial, viral, or fungal infections.
- Known to be human immunodeficiency virus (HIV) positive or has untreated, active hepatitis B.
- History of major organ transplant.
- History of an autologous/allogenic bone marrow transplant.
- Serious nonmalignant disease.
- Pregnant or nursing.
- 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.
- Symptomatic central nervous system (CNS) malignancy or metastasis.
- Clinically significant peripheral neuropathy
- Known osteoblastic bony metastasis.
- Treatment with surgery or chemotherapy within 21 days prior to study entry or radiation within 14 days of study entry.
- Previously treated with an anti-Dkk-1 therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
University of Southern California
Los Angeles, California, 90033, United States
Yale University
New Haven, Connecticut, 06520, United States
Massachusetts General Hospital
Boston, Massachusetts, 02214, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Columbia University Medical Center
New York, New York, 10032, United States
University Hospitals, Case Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Related Publications (1)
Goyal L, Sirard C, Schrag M, Kagey MH, Eads JR, Stein S, El-Khoueiry AB, Manji GA, Abrams TA, Khorana AA, Miksad R, Mahalingam D, Zhu AX, Duda DG. Phase I and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer. Clin Cancer Res. 2020 Dec 1;26(23):6158-6167. doi: 10.1158/1078-0432.CCR-20-1310. Epub 2020 Sep 2.
PMID: 32878766DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 18, 2015
First Posted
March 3, 2015
Study Start
June 1, 2015
Primary Completion
July 1, 2018
Study Completion
July 1, 2018
Last Updated
August 3, 2025
Record last verified: 2025-07