Hepatocellular CarcinomaPhase 1/2NCT03645980
DKN-01 Inhibition in Advanced Liver Cancer
A Phase 1/2 study testing DKN-01 300 mg, DKN-01 600 mg and Sorafenib in people with Hepatocellular Carcinoma, run by Johannes Gutenberg University Mainz at 6 sites in Germany.
Trial summary
This clinical trial is a prospective, open label, single arm oncological phase I/II trial in patients with hepatocellular carcinoma and WNT signaling alterations. The trial consists of two parts: Part A is a phase I study investigating the safety of DKN-01 administered as mono- as well as combination therapy with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- DKN-01 300 mg, DKN-01 600 mg and Sorafenib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 6 sitesGermany
- Study dates
- 10 Oct 2018to 31 Aug 2022
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ambulatory male or female patients ≥ 18 years
- Patients must have histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of advanced stage or recurrent diagnosis of HCC based on histopathologic findings.
- Tumor tissue is mandatory for pre-treatment evaluation (baseline) (fresh biopsy during 4-weeks screening time preferred. Archived specimen is only acceptable, if ≤ 6 months old. Baseline tumor biopsy samples must be available prior to the first dose of DKN-01.
- Tumor tissue (FFPE) must be received by central histopathology laboratory for correlative studies (fine needle aspiration and bone metastasis samples are not acceptable).
- Patients with activated WNT/β-catenin signaling identified by glutamine synthetase staining (high positive staining in tumor tissue) by an approved lab. Positive staining must be confirmed prior to first dose of DKN-01.
- Child-Pugh score <7 (Child-Pugh Class A).
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- Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to resection, locoregional therapy or refractory to locoregional therapy.
- At least one tumor lesion measurable on radiographic imaging as defined by mRECIST for HCC that has not been previously treated by locoregional therapies.
- Locoregional therapies or radiation therapy must be completed at least 4 weeks prior to baseline scan. All toxic effects > grade 1 (NCI CTCAE v5.0) related to any prior HCC treatment must be resolved. Palliative radiotherapy for symptomic control is acceptable and no additional radiotherapy for the same lesion is planned. (like bone metastases should not be targets for RECIST).
- ECOG performance status (PS) of 0 or 1.
- Estimated life expectancy of at least 3 months, in the judgment of the Investigator.
- Disease-free of active second/secondary or prior malignancies for ≥2 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast.
- Patients are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:
- HBV-HCC: Resolved HBV infection (as evidenced by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen) or chronic HBV infection (as evidenced by detectable HBV surface antigen or HBV DNA). Patients with chronic HBV infection must have HBV DNA < 2000 IU/mL and must be on antiviral therapy.
- HCV-HCC: Active or resolved HCV infection as evidenced by detectable HCV RNA or antibody
- Acceptable liver function:
- Total bilirubin ≤2.0 × upper limit of normal (ULN).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × ULN.
- Acceptable renal function:
- o Calculated creatinine clearance ≥50 mL/min using the Cockcroft and Gault Method (Cockroft and Gault 1976).
- Acceptable hematologic status:
- Neutrophil Granulocyte ≥1500 cells/μl.
- Hemoglobin ≥ 8,5 g/dL (transfusion permitted within 30 days of study entry).
- Platelet count ≥75,000 cells/μl.
- Acceptable coagulation status:
- o INR ≤ 1.7 and no active bleeding, (i.e., no clinically significant bleeding within 14 days prior to first dose of study therapy
- Female subjects who are post-menopausal (defined as spontaneous amenorrhea for at least a year) or permanently sterilized (e.g. bilateral oophorectomy, hysterectomy, bilateral salpingectomy) can participate in the trial and are not required to use any contraception.
- Women of child bearing potential (WOCBP, a woman is considered of childbearing potential i.e. fertile, following menarche and until becoming post-menopausal) must have a negative serum or urine pregnancy test within 7 days prior to first dose of DKN- 01. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG.
- Women of childbearing potential must be willing to practice a highly effective and medically accepted contraception method during trial and for 18 months after last dose of study drug. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:
- combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system ( IUS)
- bilateral tubal occlusion
- vasectomised partner (medical assessment must be present and done)
- sexual abstinence when this is in line with the preferred and usual lifestyle of the subject
- Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.
- Sexually-active male subjects must be willing to use contraception (condom, contraception for non-pregnant WOCBP partner) with their partners throughout the study and for 18 months after last dose of study drug and agree to inform the Investigator if the respective partner becomes pregnant during this time
- Provided written informed consent prior to any study-specific procedures.
- Ability of patient to understand nature, importance and individual consequences of clinical trial.
Who cannot join
- Patients with the following histology of hepatocellular cancer are not eligible for enrollment: fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
- New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
- Specific cardiac preconditions : Fridericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome. Any ECG abnormality that in the opinion of the Investigator would preclude safe participation in the study; patients with pacemakers where QTc is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study.
- Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
- Known to be human immunodeficiency virus (HIV) positive,
- History of major organ transplant (i.e., heart, lungs, liver, or kidney).
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- History of autologous/allogenic bone marrow transplant.
- Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or Sponsor.
- Pregnancy or nursing.
- Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks prior to treatment start (minor procedures within 1 week)
- History of osteonecrosis of the hip or evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that are symptomatic and clinically significant. Degenerative changes of the hip joint are not exclusionary. Screening of asymptomatic patients is not required.
- Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not required.
- Known osteoblastic bone metastasis. Screening of asymptomatic patients without a history of metastatic bone lesions is not required.
- Medical or psychological conditions that would jeopardise an adequate and orderly completion of the trial.
- Thrombotic or embolic events (except HCC tumor thrombus <pVT4) within the past 6 months (including cerebrovascular accidents)
- Evidence of portal hypertension with bleeding esophageal or gastric varices within the past 6 months
- Patients with portal vein thrombosis = pVT4
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites, 6 recruiting
- Recruiting
Universitätsklinikum Köln
Cologne, 50937
Dirk-Thomas Waldschmidt, Dr. med
- Recruiting
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Henning Wege, PD Dr.
- Recruiting
Med. Hochschule Hannover
Hanover, 30625
Arndt Vogel, Prof Dr med
- Recruiting
Universitätsklinikum Schleswig Holstein Campus Lübeck
Lübeck, 23538
Jens Marquardt, Professor, Jens.Marquardt@uksh.de
- Recruiting
Universitätsmedizin Mainz, I. Med. Klinik und Poliklinik
Mainz, 55131
Jens U Marquardt, Dr.med., +49 6131 17 ext. 6863, marquarj@uni-mainz.de
- Recruiting
II. Medizinische Universitätsklinik Gastroenterologie, Hepatologie, Infektiologie
Mannheim, 68167
Andreas Teufel, Professor, studien.med2@umm.de
About this study
Official title: A Phase I/II Multicenter, Open-label Study of DKN-01 to Investigate the Anti-tumor Activity and Safety of DKN-01 in Patients With Hepatocellular Carcinoma and WNT Signaling Alterations
This clinical trial is a prospective, open label, single arm oncological phase I/II trial in patients with hepatocellular carcinoma and WNT signaling alterations. The trial consists of two parts: Part A is a phase I study investigating the safety of DKN-01 administered as mono- as well as combination therapy with sorafenib in a 2 step dose escalation.Part B is a phase II study to investigate the anti-tumor activity and safety of DKN-01 in patients with advanced HCC. DKN-01 is administered at the recommend phase II dose (RP2D) for monotherapy and at the recommend phase II dose for combination therapy established in Part A.
Read the detailed description
Part A is a phase I study investigating the safety of DKN-01 administered as mono- as well as combination therapy with sorafenib in a 2 step dose escalation. Up to 20 patients with advanced HCC will be included in Part A. Tumor assessment will be performed every 8 weeks.The first 10 patients (cohort 1) will start with IV infusion of 300 mg DKN-01 on day 1 and 15 (monotherapy for 28 days). DLTs will be determined. After cycle 2 of monotherapy patients of cohort 1 will continue with combination of 300 mg DKN-01 IV on day 1 and 15 and sorafenib (recommended dose 800 mg per day or at discretion of the investigator) until disease progression. After 2 cycles of combination therapy and prior to the start of the next cohort DLTs will be determined. Part B is a phase II study to investigate the anti-tumor activity and safety of DKN-01 in patients with advanced HCC. DKN-01 is administered at the recommend phase II dose (RP2D) for monotherapy and at the recommend phase II dose for combination therapy established in Part A. Depending on the tolerability, the doses may be different for monotherapy and for combination therapy. Up to 50 additional patients with advanced HCC may be enrolled in Part B. Every 8 weeks tumor assessment will be performed. If progression of disease (PD1) is observed with DKN-01 monotherapy, patients will continue on study receiving DKN-01 at the recommend phase II dose for combination therapy.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- DKN-01 300 mg, DKN-01 600 mg, Sorafenib
- Keywords
- DKN-01, Hepatocellular Carcinoma, WNT signaling
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DKN-01 300 mgDrug
DKN-01 will be administered intravenous (IV) over a minimum of 30 minutes and up to a maximum of 2 hours given on days 1 and 15 of each 28 day cycle.
DKN-01 600 mgDrug
DKN-01 will be administered intravenous (IV) over a minimum of 30 minutes and up to a maximum of 2 hours given on days 1 and 15 of each 28 day cycle.
SorafenibDrug
For combination with DKN-01, sorafenib will be administrated according to standard clinical practice. Part A: After 8 weeks monotherapy with DKN-01, the study will be continued as combination therapy of DKN-01 and sorafenib until objective disease progression (PD) or unacceptable toxicity occurs. Part B:After PD1, study treatment will be continued as combination therapy of DKN-01 and sorafenib until disease progression (PD2) or unacceptable toxicity occurs.
| Study group | Role | What they receive |
|---|---|---|
| DKN-01 300 mg | Experimental | Phase I Study treatment will be started as monotherapy with DKN-01 for up to 8 weeks or until unacceptable toxicity occurs. The study will be continued as combination therapy of DKN-01 and sorafenib until objective disease progression (PD) or unacceptable toxicity occurs. The dose of DKN-01 for cohort 1 will be 300 mg , depending on the results of the safety assessment. Phase II The dose of DKN-01 will be the recommended phase II dose (RP2D) determined from Part A. Study treatment will be started as monotherapy with DKN-01 until objective disease progression (PD1) or unacceptable toxicity occurs. After PD1, study treatment will be continued as combination therapy of DKN-01 and sorafenib until disease progression (PD2) or unacceptable toxicity occurs. Receives: Drug: DKN-01 300 mg; Drug: Sorafenib |
| DKN-01 600 mg | Experimental | Phase I Study treatment will be started as monotherapy with DKN-01 for up to 8 weeks or until unacceptable toxicity occurs. The study will be continued as combination therapy of DKN-01 and sorafenib until objective disease progression (PD) or unacceptable toxicity occurs. The dose of DKN-01 for cohort 2 will be 600 mg or 150 mg, depending on the results of the safety assessment. Phase II The dose of DKN-01 will be the recommended phase II dose (RP2D) determined from Part A. Study treatment will be started as monotherapy with DKN-01 until objective disease progression (PD1) or unacceptable toxicity occurs. After PD1, study treatment will be continued as combination therapy of DKN-01 and sorafenib until disease progression (PD2) or unacceptable toxicity occurs. Receives: Drug: DKN-01 600 mg; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Adverse Events
Absolute and relative incidences of treatment-emergent adverse events.
Measured: assessment period is 2 cycles for monotherapy (each cycle is 28 days)
Phase I: Adverse Events
Absolute and relative incidences of treatment-emergent adverse events.
Measured: assessment period is 2 cycles for combination therapy (each cycle is 28 days)
Phase II: Time to progression (TTP2)
The TTP2 is defined as the time from the first DKN-01 intake until PD2. Tumor progression is assessed by mRECIST criteria (modified Response Evaluation Criteria in Solid Tumors).
Measured: time from the first DKN-01 intake until PD2, assessed up to 2 years
Secondary outcomes (7)
Phase I: pharmacokinetics of DKN-01
Serum DKN-01 levels to characterize the pharmacokinetics of DKN-01 when administered at the dose of 300 mg and 600 mg as monotherapy and in combination with sorafenib
Measured: monotherapy for 8 weeks and in combination with sorafenib for 8 weeks
Phase II: Overall survival (OS)
Overall survival is defined as the time from first DKN-01 intake until death from any cause, assessed up to 2 years
Measured: time from first DKN-01 intake until death from any cause, assessed up to 2 years
Phase II: progression free survival (PFS1, PFS2)
Progression free survival (PFS1, PFS2) is defined as the time from first DKN-
01 intake until death or PD1 or PD2 respectively whichever comes first, assessed up to 2 years
Measured: time from first DKN- 01 intake until death or PD1 or PD2 respectively whichever comes first, assessed up to 2 years
Phase II:objective response rate (ORR)
ORR (CR or PR), binary measurement
Measured: 2, 4 and 6 months after first DKN- 01 intake
Phase II: disease control rate (DCR)
DCR (CR, PR or SD), binary measurement (CR, PR or SD) after 2, 4 and 6 months will be analyzed by absolute and relative frequencies.
Measured: 2, 4 and 6 months after first DKN- 01 intake
Phase II: Duration of disease control with DKN-01
Duration of disease control is defined as the time from the first to the last occurrence of disease control (CR, PR, or SD), assessed up to 2 years
Measured: time from first to the last disease control (CR, PR, or SD), assessed up to 2 years
Phase II: Adverse Events
Absolute and relative incidences of treatment-emergent adverse events as assessed by NCI CTCAE v5.0
Measured: assessment period is during mono- and combination therapy with sorafenib (through study completion, estimated 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start10 Oct 2018
- Primary completion31 Aug 2021 (estimated)
- Study completion31 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johannes Gutenberg University Mainz
- Sponsor type
- University, hospital or other
- Collaborators
- Leap Therapeutics, Inc.
- Responsible party
- Principal investigator, Dr. J. U. Marquardt, Johannes Gutenberg University Mainz
- Investigators
- Jens U Marquardt, Dr med, Principal investigator, Universitätsklinikum Schleswig Holstein Campus Lübeck
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03645980
- Sponsor's protocol ID
- Dial-1
- Other IDs
- 2017-002468-41, AIO-HEP-0318, 2017
- Status last verified
- Oct 2020
- First submitted
- 17 Aug 2018
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Multicenter, Open-label Study of DKN-01 to Investigate the Anti-tumor Activity and Safety of DKN-01 in Patients With Hepatocellular Carcinoma and WNT Signaling Alterations
- ClinicalTrials.gov ID
- NCT03645980
- Acronym / sponsor ID
- Dial-1
- Conditions
- Hepatocellular Carcinoma
- Keywords
- DKN-01, Hepatocellular Carcinoma, WNT signaling
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Johannes Gutenberg University MainzUniversity, hospital or other
- Collaborators
- Leap Therapeutics, Inc.
- Study start
- 10 Oct 2018 (actual)
- Primary completion
- 31 Aug 2021 (estimated)
- Study completion
- 31 Aug 2022 (estimated)
- First posted
- 24 Aug 2018 (actual)
- 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.
This clinical trial is a prospective, open label, single arm oncological phase I/II trial in patients with hepatocellular carcinoma and WNT signaling alterations. The trial consists of two parts: Part A is a phase I study investigating the safety of DKN-01 administered as mono- as well as combination therapy with sorafenib in a 2 step dose escalation.Part B is a phase II study to investigate the anti-tumor activity and safety of DKN-01 in patients with advanced HCC. DKN-01 is administered at the recommend phase II dose (RP2D) for monotherapy and at the recommend phase II dose for combination therapy established in Part A.
Detailed description
Part A is a phase I study investigating the safety of DKN-01 administered as mono- as well as combination therapy with sorafenib in a 2 step dose escalation. Up to 20 patients with advanced HCC will be included in Part A. Tumor assessment will be performed every 8 weeks.The first 10 patients (cohort 1) will start with IV infusion of 300 mg DKN-01 on day 1 and 15 (monotherapy for 28 days). DLTs will be determined. After cycle 2 of monotherapy patients of cohort 1 will continue with combination of 300 mg DKN-01 IV on day 1 and 15 and sorafenib (recommended dose 800 mg per day or at discretion of the investigator) until disease progression. After 2 cycles of combination therapy and prior to the start of the next cohort DLTs will be determined. Part B is a phase II study to investigate the anti-tumor activity and safety of DKN-01 in patients with advanced HCC. DKN-01 is administered at the recommend phase II dose (RP2D) for monotherapy and at the recommend phase II dose for combination therapy established in Part A. Depending on the tolerability, the doses may be different for monotherapy and for combination therapy. Up to 50 additional patients with advanced HCC may be enrolled in Part B. Every 8 weeks tumor assessment will be performed. If progression of disease (PD1) is observed with DKN-01 monotherapy, patients will continue on study receiving DKN-01 at the recommend phase II dose for combination therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DKN-01 300 mg | Experimental | Drug: DKN-01 300 mg, Drug: SorafenibPhase I Study treatment will be started as monotherapy with DKN-01 for up to 8 weeks or until unacceptable toxicity occurs. The study will be continued as combination therapy of DKN-01 and sorafenib until objective disease progression (PD) or unacceptable toxicity occurs. The dose of DKN-01 for cohort 1 will be 300 mg , depending on the results of the safety assessment. Phase II The dose of DKN-01 will be the recommended phase II dose (RP2D) determined from Part A. Study treatment will be started as monotherapy with DKN-01 until objective disease progression (PD1) or unacceptable toxicity occurs. After PD1, study treatment will be continued as combination therapy of DKN-01 and sorafenib until disease progression (PD2) or unacceptable toxicity occurs. |
| DKN-01 600 mg | Experimental | Drug: DKN-01 600 mg, Drug: SorafenibPhase I Study treatment will be started as monotherapy with DKN-01 for up to 8 weeks or until unacceptable toxicity occurs. The study will be continued as combination therapy of DKN-01 and sorafenib until objective disease progression (PD) or unacceptable toxicity occurs. The dose of DKN-01 for cohort 2 will be 600 mg or 150 mg, depending on the results of the safety assessment. Phase II The dose of DKN-01 will be the recommended phase II dose (RP2D) determined from Part A. Study treatment will be started as monotherapy with DKN-01 until objective disease progression (PD1) or unacceptable toxicity occurs. After PD1, study treatment will be continued as combination therapy of DKN-01 and sorafenib until disease progression (PD2) or unacceptable toxicity occurs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Ambulatory male or female patients ≥ 18 years
- Patients must have histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of advanced stage or recurrent diagnosis of HCC based on histopathologic findings.
- Tumor tissue is mandatory for pre-treatment evaluation (baseline) (fresh biopsy during 4-weeks screening time preferred. Archived specimen is only acceptable, if ≤ 6 months old. Baseline tumor biopsy samples must be available prior to the first dose of DKN-01.
- Tumor tissue (FFPE) must be received by central histopathology laboratory for correlative studies (fine needle aspiration and bone metastasis samples are not acceptable).
- Patients with activated WNT/β-catenin signaling identified by glutamine synthetase staining (high positive staining in tumor tissue) by an approved lab. Positive staining must be confirmed prior to first dose of DKN-01.
Key exclusion criteria (17 listed)
- Patients with the following histology of hepatocellular cancer are not eligible for enrollment: fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
- New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
- Specific cardiac preconditions : Fridericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome. Any ECG abnormality that in the opinion of the Investigator would preclude safe participation in the study; patients with pacemakers where QTc is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study.
- Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
- Known to be human immunodeficiency virus (HIV) positive,
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-01 300 mgDKN-01 will be administered intravenous (IV) over a minimum of 30 minutes and up to a maximum of 2 hours given on days 1 and 15 of each 28 day cycle. | Drug | DKN-01 300 mg |
| DKN-01 600 mgDKN-01 will be administered intravenous (IV) over a minimum of 30 minutes and up to a maximum of 2 hours given on days 1 and 15 of each 28 day cycle. | Drug | DKN-01 600 mg |
| SorafenibFor combination with DKN-01, sorafenib will be administrated according to standard clinical practice. Part A: After 8 weeks monotherapy with DKN-01, the study will be continued as combination therapy of DKN-01 and sorafenib until objective disease progression (PD) or unacceptable toxicity occurs. Part B:After PD1, study treatment will be continued as combination therapy of DKN-01 and sorafenib until disease progression (PD2) or unacceptable toxicity occurs. | Drug | DKN-01 300 mg, DKN-01 600 mg |
Primary outcome
Phase I: Adverse Events
Time frame: assessment period is 2 cycles for monotherapy (each cycle is 28 days)
Absolute and relative incidences of treatment-emergent adverse events.
Phase I: Adverse Events
Time frame: assessment period is 2 cycles for combination therapy (each cycle is 28 days)
Absolute and relative incidences of treatment-emergent adverse events.
Phase II: Time to progression (TTP2)
Time frame: time from the first DKN-01 intake until PD2, assessed up to 2 years
The TTP2 is defined as the time from the first DKN-01 intake until PD2. Tumor progression is assessed by mRECIST criteria (modified Response Evaluation Criteria in Solid Tumors).
7 secondary outcomes
Phase I: pharmacokinetics of DKN-01
Time frame: monotherapy for 8 weeks and in combination with sorafenib for 8 weeks
Phase II: Overall survival (OS)
Time frame: time from first DKN-01 intake until death from any cause, assessed up to 2 years
Phase II: progression free survival (PFS1, PFS2)
Time frame: time from first DKN- 01 intake until death or PD1 or PD2 respectively whichever comes first, assessed up to 2 years
Phase II:objective response rate (ORR)
Time frame: 2, 4 and 6 months after first DKN- 01 intake
Phase II: disease control rate (DCR)
Time frame: 2, 4 and 6 months after first DKN- 01 intake
Phase II: Duration of disease control with DKN-01
Time frame: time from first to the last disease control (CR, PR, or SD), assessed up to 2 years
Phase II: Adverse Events
Time frame: assessment period is during mono- and combination therapy with sorafenib (through study completion, estimated 2 years)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
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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.
Jens U Marquardt, Dr med principal investigator
Universitätsklinikum Schleswig Holstein Campus Lübeck
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DKN-01 300 mg, DKN-01 600 mg and Sorafenib in people with Hepatocellular Carcinoma, run by Johannes Gutenberg University Mainz at 6 sites in Germany.
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 40 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jens U Marquardt, Dr med (++49 451 500 ext. 44100, Jens.Marquardt@uksh.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Adverse Events (time frame: assessment period is 2 cycles for monotherapy (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Oct 2020.