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

Cholangiocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02375880
• Other study ID #: DEK-DKK1-P103
• Status: Completed
• Phase: Phase 1
• 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
• 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

Related Conditions & MeSH terms

• Bile Duct Cancer
• Bile Duct Neoplasms
• Carcinoma
• Carcinoma of Gallbladder
• Carcinoma of Intrahepatic and Extra-hepatic Biliary System
• Cholangiocarcinoma

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