Carcinoma of Intrahepatic and Extra-hepatic Biliary SystemPhase 1NCT02375880
Study of DKN-01 and Gemcitabine/Cisplatin in Patients With Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder
A Phase 1 study testing DKN-01, gemcitabine and cisplatin in people with Carcinoma of Intrahepatic and Extra-hepatic Biliary System and Carcinoma of Gallbladder, run by Leap Therapeutics, Inc. at 9 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Carcinoma of Intrahepatic and Extra-hepatic Biliary System, Carcinoma of Gallbladder, Bile Duct Cancer
- What is being tested?
- DKN-01, gemcitabine and cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 9 sitesUnited States
- Study dates
- Jun 2015to Jul 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
- Other exclusions apply
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Massachusetts General Hospital
Boston, Massachusetts, 02214
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University Hospitals, Case Medical Center
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
University of Southern California
Los Angeles, California, 90033
Yale University
New Haven, Connecticut, 06520
Columbia University Medical Center
New York, New York, 10032
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
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
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.
Read the 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.
- Conditions
- Carcinoma of Intrahepatic and Extra-hepatic Biliary System, Carcinoma of Gallbladder, Bile Duct Cancer, Cholangiocarcinoma
- Being tested
- DKN-01, gemcitabine, cisplatin
- Medical subject headings
- Gallbladder Neoplasms, Bile Duct Neoplasms, Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DKN-01Drug
Also called LY2812176
Administration by intravenous (IV) infusion.
gemcitabineDrug
Also called Gemzar
Administered by IV infusion.
cisplatinDrug
Also called Platinol
Administered by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 150 mg DKN-01 Part A | Experimental | 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. Receives: Drug: DKN-01; Drug: gemcitabine; Drug: cisplatin |
| 300 mg DKN-01 Part A | Experimental | 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. Receives: Drug: DKN-01; Drug: gemcitabine; Drug: cisplatin |
| MTD mg DKN-01 Part B | Experimental | 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. Receives: Drug: DKN-01; Drug: gemcitabine; Drug: cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Parts A and B: at a minimum Days 1, 8, 15 of each treatment cycle.
Secondary outcomes (4)
Pharmacokinetics - AUC
Plasma levels will be measured during the treatment period.
Measured: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Pharmacokinetics - Cmax
Plasma levels will be measured during the treatment period.
Measured: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Pharmacokinetics - Tmax
Plasma levels will be measured during the treatment period.
Measured: 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)
Response to treatment evaluated using the Response Evaluation Criteria in Solid Tumors guidelines (RECIST 1.1).
Measured: At baseline, prior to the start of Cycle 3, and every 2 cycles thereafter until disease progression or death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study startJun 2015
- Primary completionJul 2018
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma of Intrahepatic and Extra-hepatic Biliary SystemStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leap Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02375880
- Sponsor's protocol ID
- DEK-DKK1-P103
- Status last verified
- Jul 2025
- First submitted
- 18 Feb 2015
- Last updated
- 3 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 32878766
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02375880
- Acronym / sponsor ID
- DEK-DKK1-P103
- Conditions
- Carcinoma of Intrahepatic and Extra-hepatic Biliary System, Carcinoma of Gallbladder, Bile Duct Cancer, Cholangiocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Leap Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2015
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 3 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 150 mg DKN-01 Part A | Experimental | Drug: DKN-01, Drug: gemcitabine, Drug: cisplatinPatients 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 | Experimental | Drug: DKN-01, Drug: gemcitabine, Drug: cisplatinPatients 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 | Experimental | Drug: DKN-01, Drug: gemcitabine, Drug: cisplatinPatients 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. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DKN-01Also: LY2812176Administration by intravenous (IV) infusion. | Drug | 150 mg DKN-01 Part A, 300 mg DKN-01 Part A, MTD mg DKN-01 Part B |
| gemcitabineAlso: GemzarAdministered by IV infusion. | Drug | 150 mg DKN-01 Part A, 300 mg DKN-01 Part A, MTD mg DKN-01 Part B |
| cisplatinAlso: PlatinolAdministered by IV infusion | Drug | 150 mg DKN-01 Part A, 300 mg DKN-01 Part A, MTD mg DKN-01 Part B |
Primary outcome
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.
4 secondary outcomes
Pharmacokinetics - AUC
Time frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Pharmacokinetics - Cmax
Time frame: Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Pharmacokinetics - Tmax
Time frame: 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)
Time frame: At baseline, prior to the start of Cycle 3, and every 2 cycles thereafter until disease progression or death
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
- Derived from this study: PubMed 32878766Goyal 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DKN-01, gemcitabine and cisplatin in people with Carcinoma of Intrahepatic and Extra-hepatic Biliary System and Carcinoma of Gallbladder, run by Leap Therapeutics, Inc. at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose and dose-limiting toxicities as determined in Part A. (time frame: End of Cycle 1 (Day 21)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02375880, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.