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Trial record 7 of 8 for:    DKN-01

A Parallel Arm Phase 1b/2a Study of DKN-01 as Monotherapy or in Combination With Docetaxel for the Treatment of Advanced Prostate Cancer With Elevated DKK1

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ClinicalTrials.gov Identifier: NCT03837353
Recruitment Status : Not yet recruiting
First Posted : February 12, 2019
Last Update Posted : March 13, 2019
Sponsor:
Collaborator:
Leap Therapeutics, Inc.
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date  ICMJE January 22, 2019
First Posted Date  ICMJE February 12, 2019
Last Update Posted Date March 13, 2019
Estimated Study Start Date  ICMJE March 30, 2019
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
  • Measure of Dose Limiting Toxicities [ Time Frame: baseline to End of Cycle 1 (each cycle is 28 days) ]
    Starting from Cohort 1 Day 1 to Cohort 2 Day 1
  • Measure of Dose Limiting Tolerability [ Time Frame: Baseline to End of Cycle 1 (each cycle is 28 days) ]
    Starting from Cohort 1 Day 1 to Cohort 2 Day 1
  • Measure of clinical response to treatment [ Time Frame: Baseline to study completion (approximately 36 Months) ]
    Repeat tumor imaging confirming PD (iCPD) by iRECIST per Investigator
  • Number of subjects with adverse drug reactions and toxicities [ Time Frame: Baseline until 30 days after last dose of study drug as assessments at a minimum of 2 weeks ]
    Evaluated by NCI CTCAE v 4.0 of DKN-01 monotherapy or in combination with docetaxel
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03837353 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Parallel Arm Phase 1b/2a Study of DKN-01 as Monotherapy or in Combination With Docetaxel for the Treatment of Advanced Prostate Cancer With Elevated DKK1
Official Title  ICMJE A Parallel Arm Phase 1b/2a Study of DKN-01 as Monotherapy or in Combination With Docetaxel for the Treatment of Advanced Prostate Cancer With Elevated DKK1
Brief Summary This is a non-randomized multi-center Phase 1b/2a dose escalation and dose expansion study involving 85-97 patients testing DKN-01 as monotherapy or in combination with docetaxel in metastatic castration-resistant prostate cancer. Patients need to be biomarker positive (Dickkopf-1 [DKK1]) either in plasma or biopsy. Other biopsies for correlative studies are encouraged but not mandatory. Pharmacokinetic (PK) testing of one pre-treatment blood sample and one post-treatment blood sample will be mandatory on Day 1 of every cycle.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: DKN-01 300 mg
    DKN-01 300 mg intravenously (IV)
  • Drug: DKN-01 600 mg
    DKN-01 600 mg IV
  • Drug: Docetaxel 75 mg/m2
    Docetaxel 75 mg/m2, Day 1 of every 3 Weeks
  • Drug: DKN-01 150 mg
    DKN-01 150 mg intravenously (IV)
Study Arms  ICMJE
  • Experimental: Cohort 1A

    Cohort 1A Dose Level 1: DKN-01 300 mg intravenously (IV) on Days 1 and 15, docetaxel 75 mg/m2 on Day 1 every 3 weeks (21- day cycles).

    Dose Level 2: DKN-01 600 mg IV on Days 1 and 15, docetaxel 75 mg/m 2 on Day 1 every 3 weeks (21-day cycles).

    Dose Level -1: DKN-01 150 mg IV on Days 1 and 15, docetaxel 75 mg/m 2 on Day 1 every 3 weeks (21-day cycles).

    Interventions:
    • Drug: DKN-01 300 mg
    • Drug: DKN-01 600 mg
    • Drug: Docetaxel 75 mg/m2
    • Drug: DKN-01 150 mg
  • Experimental: Cohort 1B
    Cohort 1B: DKN-01 at MTD or highest dose tested: Days 1 and 15, docetaxel 75 mg/m2 Day 1 of every 3 weeks (21-day cycles)
    Interventions:
    • Drug: DKN-01 300 mg
    • Drug: DKN-01 600 mg
    • Drug: Docetaxel 75 mg/m2
    • Drug: DKN-01 150 mg
  • Experimental: Cohort 1C
    Cohort 1C: DKN-01 at MTD or highest dose tested: Days 1 and 15, docetaxel 75 mg/m2 Day 1 of every 3 weeks (21-day cycles)
    Interventions:
    • Drug: DKN-01 300 mg
    • Drug: DKN-01 600 mg
    • Drug: Docetaxel 75 mg/m2
    • Drug: DKN-01 150 mg
  • Experimental: Cohort 2A

    Dose Level 1: DKN-01 300 mg IV on Days 1 and 15 of a 28-day cycle. Dose Level 2: DKN-01 600 mg IV on Days 1 and 15 of a 28-day cycle.

    Dose Level -1: DKN-01 150 mg IV on Days 1 and 15 of a 28-day cycle.

    Interventions:
    • Drug: DKN-01 300 mg
    • Drug: DKN-01 600 mg
    • Drug: DKN-01 150 mg
  • Experimental: Cohort 2B
    Cohort 2B: DKN-01 at MTD or highest dose tested: Days 1 and 15 (28-day cycles)
    Interventions:
    • Drug: DKN-01 300 mg
    • Drug: DKN-01 600 mg
    • Drug: DKN-01 150 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 8, 2019)
97
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have a histologically or cytologically confirmed prostate adenocarcinoma or poorly differentiated carcinoma of the prostate
  • Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to C1D1 and must be continued throughout the study.
  • Cohorts 1A, 1B, and 1C. Patients must have received 1 or more androgen receptor (AR) signaling inhibitors (abiraterone or enzalutamide) and have not received prior taxane-based chemotherapy for prostate cancer. Prior treatment with an AR signaling inhibitor for castration-sensitive disease will be allowed if the time to progression was within 1 year after starting drug. Prior treatment with a taxane-based chemotherapy for castration-sensitive disease will be exclusionary.
  • Cohorts 2A and 2B. Patients must have received 1 or more AR signaling inhibitor (abiraterone or enzalutamide) and either had disease progression, were intolerant of, or refused 1 or more taxane-based chemotherapies for mCRPC.
  • Patients must be DKK1-high as determined by either:

    1. Elevated DKK1 RNA expression in ≥1% of cells as defined by central laboratory testing of a fresh biopsy or archival specimen OR
    2. DKK1 protein level in peripheral blood plasma that is above the reference limit of a cohort of healthy male controls as established by central laboratory testing
  • Cohort 1B. Patients must have progression of measurable disease per mRECIST v1.1 guidelines.
  • Cohort 1C. Patients must have progression of disease defined as one of the following:

    1. PSA progression is defined by Prostate Cancer Working Group 3 (PCWG3) criteria as a minimum of two consecutive rising levels, with an interval of ≥1 week between each determination with a minimum PSA of 2 ng/mL.
    2. Radionuclide bone progression as defined by at least two new metastatic lesions (per PCWG3).
  • Cohorts 1A, 2A, 2B. Patients must have baseline progression defined as one of the following:

    1. PSA progression is defined by PCWG3 criteria as a minimum of two consecutive rising levels, with an interval of ≥1 week between each determination with a minimum PSA of 2 ng/mL.
    2. Radionuclide bone progression as defined by at least two new metastatic lesions (per PCWG3).
    3. Soft tissue progression on transaxial imaging: new or progressive soft tissue masses on computed tomography (CT) or magnetic resonance imaging (MRI) scans as defined by mRECIST v1.1.
  • Eastern Cooperative Oncology Group (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.
  • Required initial laboratory values within 14 days of C1D1:

    1. Total bilirubin within normal limits for the institution. (For Cohorts 2A and 2B, total bilirubin < 3 × ULN is acceptable with known liver metastases).
    2. Transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] ≤1.5 × the upper limit of normal (ULN) OR alkaline phosphatase ≤2.5 × ULN (For Cohorts 2A and 2B, AST and ALT and alkaline phosphatase ≤ 5.0 × ULN is acceptable with known liver metastases).
    3. Creatinine ≤2.0 or calculated creatinine clearance ≥50 mL/min using the Cockcroft and Gault Method (Cockroft and Gault 1976).
    4. Absolute neutrophil count ≥1000 cells/μl.
    5. Absolute lymphocyte count ≥500/μl.
    6. Hemoglobin ≥9.0 g/dL.
    7. Platelet count ≥100,000 cells/μl. (For Cohorts 2A and 2B, Platelet count ≥75,000 cells/μl).
    8. International normalized ratio (INR) (prothrombin time [PT])/ partial thromboplastin time (PTT) ≤1.2 × ULN unless receiving anticoagulant, in which case INR ≤3.0 and no active bleeding, (ie, no clinically significant bleeding within 14 days prior to first dose of study therapy.
  • Sexually active male patients must agree to use adequate contraception (hormonal or barrier method of birth control) during the study and for 6 months after their last dose of study drug. Should a patient's partner become pregnant or suspect she is pregnant while participating in the study, the Investigator should be immediately informed.
  • Reliable and willing to make themselves available for the duration of the study and are willing to follow study-specific procedures.
  • Provided written informed consent prior to any study-specific procedures.

Exclusion Criteria:

  • Any anti-cancer therapy (with the exception of luteinizing hormonereleasing hormone [LHRH] analog or antagonist) within 2 weeks prior to initiation of study treatment.
  • Any investigational anti-cancer therapy within 4 weeks of initiation of study treatment.
  • Histological small cell or pure neuroendocrine carcinoma that has not yet been treated with at least one line of platinum-based chemotherapy (Prostate adenocarcinoma with immunohistochemical neuroendocrine differentiation but without histological small cell that is naïve to platinumbased chemotherapy will be allowed.)
  • New York Heart Association Class III or IV heart failure, or myocardial infarction within the past 6 months, or unstable arrhythmia within 3 months.
  • Uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry.
  • Known to be human immunodeficiency virus (HIV) positive, have positive hepatitis B surface antigen (HBSAg), or positive hepatitis C antibody (HCAb) test. (Hepatitis C antibody-positive patients with an undetectable hepatitis C virus (HCV) RNA will be eligible.)
  • History of solid organ transplant (ie, heart, lungs, liver, or kidney).
  • History of autologous/allogenic bone marrow transplant.
  • Serious nonmalignant disease that could compromise protocol objectives in the opinion of the Investigator and/or Sponsor.
  • Major surgical procedures or significant traumatic injury within 4 weeks prior to study entry (minor procedures within 1 week of study entry).
  • History of osteonecrosis of the hip. Other hip pathology such as degenerative disease or malignant involvement are not exclusionary. Screening of asymptomatic patients is not required.
  • Active or untreated central nervous system (CNS) malignancy or metastasis. Screening for CNS metastases of asymptomatic patients without a history of CNS metastases is not required. Patients with treated
  • CNS metastases are eligible provided they meet all of the following criteria:

    1. Evaluable disease outside the CNS.
    2. No history of intracranial or intraspinal hemorrhage.
    3. No evidence of significant vasogenic edema.
    4. No ongoing requirement for corticosteroids as therapy for CNS disease. (Anti-convulsants at a stable dose for > one month is allowed.)
    5. No stereotactic radiation, whole brain radiation within 4 weeks of C1D1.
    6. Patients with CNS metastases treated by neurosurgical resection or brain biopsy within 3 month prior to C1D1 will not be allowed.
    7. Radiographic demonstration of interim stability (ie, no progression) between completion of CNS-directed therapy and the screening radiographic study.
    8. Screening CNS radiographic study ≥4 weeks since completion of radiotherapy or surgical resection and ≥2 weeks since discontinuation of corticosteroids.
  • Any other condition, disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
  • Active substance abuse.
  • Receipt of any live vaccine within 30 days before the first dose of study treatment or anticipation that such a live vaccine will be required during study.
  • Previously treated with an anti-DKK1 therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Casey Konys (212)-263-1208 casey.konys@nyumc.org
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03837353
Other Study ID Numbers  ICMJE 17-01747
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
Access Criteria: The investigator who proposed to use the data.
Responsible Party NYU Langone Health
Study Sponsor  ICMJE NYU Langone Health
Collaborators  ICMJE Leap Therapeutics, Inc.
Investigators  ICMJE
Principal Investigator: David Wise, MD New York Langone Medical Center
PRS Account NYU Langone Health
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP