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A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab (P102)

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ClinicalTrials.gov Identifier: NCT02013154
Recruitment Status : Recruiting
First Posted : December 17, 2013
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Leap Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE December 11, 2013
First Posted Date  ICMJE December 17, 2013
Last Update Posted Date April 25, 2019
Study Start Date  ICMJE January 2014
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2017)
  • Number of subjects with dose limiting toxicities in Study Parts A and F which will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03 [ Time Frame: Baseline to End of cycle 1 (Part A cycle is 28 days and Part F cycle is 21 days) ]
  • Number of subjects with adverse drug reactions and toxicities as evaluated by NCI CTCAE v4.03 of DKN-01 as monotherapy or in combination with paclitaxel or pembrolizumab [ Time Frame: Baseline until 30 days after last dose of study drug as assessed at a minimum of every 2 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2013)
The Maximum Tolerated Dose, and Number of Participants with Dose Limiting Toxicities [ Time Frame: Baseline to end of cycle (approximately 4 weeks) ]
Change History Complete list of historical versions of study NCT02013154 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2017)
  • Clinical response to treatment [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Objective Response Rate (ORR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Objective Disease Control Rate (ODCR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Duration of Response (DoR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Duration of CR (DoCR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Overall Survival (OS) [ Time Frame: Baseline to study completion (approximately 3 months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2013)
  • Overall Response Rate (ORR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Duration of Response [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Overall Survival [ Time Frame: Baseline to study completion (approximately 3 months) ]
  • Summary Statistics of DKN-01 Serum Concentrations [ Time Frame: Cycle 1 Day 1 pre-dose to Cycle 2 Day 1 pre-dose (approximately 4 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab
Official Title  ICMJE A Multi-part, Phase 1, Multi-center, Open-label Study of DKN-01 as a Monotherapy or in Combination With Paclitaxel or Pembrolizumab in Patients With Relapsed or Refractory Esophagogastric Malignancies
Brief Summary A study to evaluate the safety and tolerability of DKN-01 in combination with weekly paclitaxel or pembrolizumab in participants with relapsed or refractory Esophagogastric Malignancies
Detailed Description

Part A is a Dose-Escalation Study in Participants with Relapsed or Refractory Esophageal Cancer or Gastro-Esophageal Junction Tumors. Parts B, C, D and E are expansion cohorts of Patients with Relapsed or Refractory Esophageal Cancer, Gastro-Esophageal Junction Tumors and Gastric Adenocarcinoma.

Part F is a Dose-Escalation and Expansion Cohorts with DKN-01 + Pembrolizumab in Patients with Recurrent or Metastatic Esophageal Cancer, Gastroesophageal Junction Cancer or Gastric Adenocarcinoma with Wnt Signaling Alterations.

Patients who are unable to receive paclitaxel or pembrolizumab for any reason will be allowed to receive single agent DKN-01 as part of a monotherapy substudy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Esophageal Neoplasms
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastroesophageal Cancer
  • Squamous Cell Carcinoma
  • Gastric Adenocarcinoma
Intervention  ICMJE
  • Drug: DKN-01
    Administered by IV infusion
  • Drug: Paclitaxel
    Administered by IV infusion
    Other Name: Taxol
  • Drug: Pembrolizumab
    Administered by IV infusion
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: Part A: DKN-01 (Dose Escalation)
    Escalating dose of 150 milligrams (mg) up to 300 mg of DKN-01 administered on days 1 and 15 and 80 milligrams per meter squared of body surface area (mg/m2) of paclitaxel administered on days 1,8,15, and 22
    Interventions:
    • Drug: DKN-01
    • Drug: Paclitaxel
  • Experimental: Part B: DKN-01 (Dose Confirmation)
    Dose of DKN-01 determined in Part A will be administered to esophageal or gastro-esophageal junction cancer patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22
    Interventions:
    • Drug: DKN-01
    • Drug: Paclitaxel
  • Experimental: Part C: DKN-01 (Cohort Expansion)
    Dose of DKN-01 determined in Part A will be administered to esophageal or gastro-esophageal junction adenocarcinoma patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22
    Interventions:
    • Drug: DKN-01
    • Drug: Paclitaxel
  • Experimental: Part D: DKN-01 (Cohort Expansion)
    Dose of DKN-01 determined in Part A will be administered to esophageal squamous cell cancer patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22
    Interventions:
    • Drug: DKN-01
    • Drug: Paclitaxel
  • Experimental: DKN-01 Monotherapy Substudy
    Dose of DKN-01 determined in Part A will be administered to esophageal or gastro-esophageal junction cancer patients on Days 1 and 15
    Intervention: Drug: DKN-01
  • Experimental: Part E: DKN-01 (Cohort Expansion)
    Dose of DKN-01 determined in Part A will be administered to gastric adenocarcinoma with Wnt signaling alteration cancer patients on Days 1 and 15 and 80 mg/m2 of paclitaxel administered on Days 1,8,15,and 22
    Interventions:
    • Drug: DKN-01
    • Drug: Paclitaxel
  • Experimental: Part F DKN-01 (Dose Escalation+Expansion)
    Escalating dose on 150mg up to 300 mg of DKN-01 administered to patients with recurrent or metastatic esophageal cancer, gastroesophageal junction cancer or gastric adenocarcinoma with Wnt signaling alterations on days 1 and 15 and 200 mg of pembrolizumab administered on day 1 of a 21 day cycle
    Interventions:
    • Drug: DKN-01
    • Drug: Pembrolizumab
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 6, 2017)
224
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2013)
32
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

In advanced esophagogastric malignancies:

  • Participants with histologically confirmed recurrent or metastatic esophageal or gastro-esophageal junction squamous cell or adenocarcinoma or gastric adenocarcinoma with Wnt Signaling Alterations
  • Participants must be refractory or intolerant to at least one prior therapy(ies) for metastatic or locally advanced disease

    • If prior therapy consisted of palliative chemoradiation therapy, it will be considered one line of therapy
    • Prior treatment with paclitaxel as part of a definitive therapy regimen is acceptable. Patients who are unable to receive paclitaxel for any reason will be allowed to receive DKN-01 as a single agent.
    • Prior treatment anti- programmed death-1 (PD-1)/ anti-PD-ligand 1 (PD-L1) monoclonal antibody (mAb) is permitted in patients provided the patient's disease is primary refractory, and the patient is not intolerant of pembrolizumab. Patients who are not eligible to receive pembrolizumab will be allowed to receive single agent DKN-01
  • Tumor tissue for mandatory evaluation
  • Must have one or more tumors measurable on radiographic imaging as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Patients with evaluable but not measurable disease per RECIST criteria may be enrolled with the approval of the medical monitor.
  • Must be ≥18 years of age
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. A performance status of 2 on the ECOG scale may be entered upon the review and approval of the medical monitor
  • Disease-free of active second/secondary or prior malignancies for equal to or over 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
  • Acceptable liver, renal, hematologic and coagulation function
  • For men and women of child-producing potential, the use of effective contraceptive methods during the study and for 6 months following the last dose of study drug

Exclusion Criteria:

  • New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia
  • 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, within 7 days of study entry requiring systemic therapy
  • Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) unless HCV RNA is undetected/negative.
  • Serious nonmalignant disease
  • Pregnant or nursing women
  • 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.
  • Systemic central nervous system (CNS) malignancy or metastasis.
  • Clinically significant peripheral neuropathy at the time of study entry. Patients with pre-existing peripheral neuropathy will be allowed to receive single agent DKN-01
  • Known osteoblastic bony metastasis
  • History of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
  • Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days for nitrosoureas or mitomycin C)
  • Treatment with low dose chemotherapy concurrent with radiation within 14 days prior to study entry
  • Treatment with radiation therapy within 14 days prior to study entry
  • Treatment with any other investigational agent within 30 days prior to study entry
  • Previously treated with an anti-DKK-1 therapy
  • Participants who have a history of hypersensitivity reactions to TAXOL® or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil). Patients who exhibit these hypersensitivities will be eligible to receive single agent DKN-01.
  • Significant allergy to a pharmaceutical therapy that, in the opinion of the investigator, poses an increased risk to the participant
  • Treatment with corticosteroids (≥ 10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to study entry
  • Active substance abuse
  • Receipt of any live vaccines within 30 days before the first dose of study treatment and while participating in the study
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • History of interstitial lung disease
  • Intolerance or severe hypersensitivity (≥Grade 3) to pembrolizumab and/or of its excipients
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cyndi Sirard csirard@leaptx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02013154
Other Study ID Numbers  ICMJE DEK-DKK1-P102
DKN-01
LY2812176
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Leap Therapeutics, Inc.
Study Sponsor  ICMJE Leap Therapeutics, Inc.
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Cyndi Sirard, MD Leap Therapeutics, Inc.
PRS Account Leap Therapeutics, Inc.
Verification Date April 2019

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