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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02375880
Other study ID # DEK-DKK1-P103
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date June 2015
Est. completion date July 2018

Study information

Verified date September 2018
Source Leap Therapeutics, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 carcinoma primary to the intra- or exta-hepatic biliary system or gallbladder.


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.


Recruitment information / eligibility

Status Completed
Enrollment 51
Est. completion date July 2018
Est. primary completion date July 2018
Accepts healthy volunteers No
Gender All
Age group 30 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
DKN-01
Administration by intravenous (IV) infusion.
gemcitabine
Administered by IV infusion.
cisplatin
Administered by IV infusion

Locations

Country Name City State
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Dana Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Cleveland Clinic Cleveland Ohio
United States University Hospitals, Case Medical Center Cleveland Ohio
United States University of Southern California Los Angeles California
United States Yale University New Haven Connecticut
United States Columbia University Medical Center New York New York
United States University of Texas Health Science Center at San Antonio San Antonio Texas

Sponsors (1)

Lead Sponsor Collaborator
Leap Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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)
Primary 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 Pharmacokinetics - AUC Plasma levels will be measured during the treatment period. Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Secondary Pharmacokinetics - Cmax Plasma levels will be measured during the treatment period. Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Secondary Pharmacokinetics - Tmax Plasma levels will be measured during the treatment period. Cycle 1 - Days 1 and 8, Cycle 2 - Day 1
Secondary 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). At baseline, prior to the start of Cycle 3, and every 2 cycles thereafter until disease progression or death
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