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Trial record 2 of 4 for:    LY2812176

A Study of DKN-01 in Combination With Paclitaxel

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Leap Therapeutics, Inc.
Sponsor:
Information provided by (Responsible Party):
Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT02013154
First received: December 11, 2013
Last updated: August 25, 2016
Last verified: August 2016
  Purpose
A study to evaluate the safety and tolerability of DKN-01 in combination with weekly paclitaxel in participants with refractory/recurrent esophageal or gastro-esophageal junction cancer.

Condition Intervention Phase
Esophageal Neoplasms
Adenocarcinoma of the Gastroesophageal Junction
Gastroesophageal Cancer
Squamous Cell Carcinoma
Drug: DKN-01
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Four Part, Phase 1, Multi-center, Open-label Study of DKN-01 in Combination With Weekly Paclitaxel; Part A: A Dose-Escalation Study in Patients With Relapsed or Refractory Esophageal Cancer or Gastro-esophageal Junction Tumors; Part B: An Expansion Cohort in Patients With Relapsed or Refractory Esophageal Cancer or Gastro-esophageal Junction Tumors; Part C: An Expansion Cohort in Patients With Relapsed or Refractory Esophageal or Gastro-esophageal Junction Adenocarcinoma; Part D: An Expansion Cohort in Patients With Relapsed or Refractory Esophageal Squamous Cell Cancer

Resource links provided by NLM:


Further study details as provided by Leap Therapeutics, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose Determined According to Incidence of Dose-Limiting Toxicity [ Time Frame: Baseline to end of cycle (approximately 4 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Estimated Enrollment: 92
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: DKN-01
Administered by IV infusion
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol
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
Drug: DKN-01
Administered by IV infusion
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol
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
Drug: DKN-01
Administered by IV infusion
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol
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
Drug: DKN-01
Administered by IV infusion
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol
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
Drug: DKN-01
Administered by IV infusion

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, and D are expansion cohorts of Patients with Relapsed or Refractory Esophageal Cancer or Gastro-Esophageal Junction Tumors.

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

  Eligibility

Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In advanced esophageal malignancies:

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

      1. If prior therapy consisted of palliative chemoradiation therapy it will be considered one line of therapy
      2. 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.
  • 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 ambulatory
  • 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
  • Have an estimated life expectancy of at least 3 months, in the judgment of the investigator
  • 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 function of:

    1. Bilirubin less than or equal to (≤) 1.5 times upper limit of normal (ULN)
    2. Aspartate aminotransferase (AST)(SGOT), alanine aminotransferase (ALT)(SGPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed)
  • Acceptable renal function:

    a. Creatinine normal for age; if serum creatinine is abnormal for age the patient must have a calculated creatinine clearance greater than or equal to (≥) 50 mL/min using the Cockcroft and Gault Method.

  • Acceptable hematologic status of:

    1. Granulocyte ≥ 1500 cells/mm3
    2. Hemoglobin ≥ 9 g/dL (transfusion permitted within 30 days of study entry)
    3. Platelet count ≥ 100,000 (plt/mm3)
  • Acceptable coagulation status:

    1. Prothrombin time/partial thromboplastin time (PT/PTT) ≤ 1.2 x ULN (unless receiving anticoagulation therapy, if receiving anticoagulation therapy, eligibility will be based upon the international normalised ratio(INR) as follows):
    2. INR ≤ 1.6 (unless receiving anticoagulation therapy). If receiving anticoagulant: INR ≤ 3.0 and no active bleeding, (i.e., no bleeding within 14 days prior to first dose of study therapy)
  • 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 Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) during the study, and must agree to use adequate contraception prior to study entry and for 6 months after their last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

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. 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, have hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) unless HCV RNA is undetected/negative.
  • History of major organ transplant (for example: heart, lungs, liver and kidney)
  • History of autologous or allogenic bone marrow transplant
  • Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
  • 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. Degenerative changes of the hip joint are not exclusionary. Screening of asymptomatic participants is not required.
  • Symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Radiation must have been completed at least 14 days prior to study entry. Screening of asymptomatic participants without a history of CNS metastases is not required
  • 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. Screening of asymptomatic participants without a history of metastatic bony lesions is not required
  • 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
  • Participants who are currently receiving any other investigational agent or have received an investigational agent within last 30 days of study entry or 5 half-lives, whichever is longer
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02013154

Contacts
Contact: Cyndi Sirard csirard@leaptx.com

Locations
United States, Connecticut
Smilow Cancer Hospital at Yale - New Haven Recruiting
New Haven, Connecticut, United States, 06520
Contact: Kirsten Dooley       kirsten.dooley@yale.edu   
Principal Investigator: Stacey Stein, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: GI Research Line    617-632-5960      
Principal Investigator: Peter Enzinger, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Susan Sheehan       ssheehan1@partners.org   
Principal Investigator: Janet Murphy, MD         
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: Tiffany Pearce    313-916-1784    tpearce1@hfhs.org   
Principal Investigator: Ding Wang, MD         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Active, not recruiting
New Brunswick, New Jersey, United States, 08903
United States, New York
Columbia University Medical Center Active, not recruiting
New York, New York, United States, 10032
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Leighanne Hartman       leighanne.hartman@duke.edu   
Principal Investigator: John Strickler, MD         
United States, Ohio
University Hospitals Recruiting
Cleveland, Ohio, United States, 44106
Contact: Cancer Information Services    800-641-2422      
Principal Investigator: Jennifer Eads, MD         
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Centre Recruiting
Cleveland, Ohio, United States, 44195
Contact: Davendra Sohal, MD    216-444-8258      
Contact: Jan Hanson, MPH    216-844-5060      
Principal Investigator: Davendra Sohal, MD         
United States, Tennessee
Tennessee Oncology / Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Amanda Risinger    615-524-4455    Amanda.Risinger@scresearch.net   
Principal Investigator: Johanna Bendell, MD         
Vanderbilt University / VICC Recruiting
Nashville, Tennessee, United States, 37232
Contact: Research Phone Number    800-811-8480      
Principal Investigator: Emily Chan, MD         
United States, Texas
Mary Crowley Cancer Center Recruiting
Dallas, Texas, United States, 75251
Contact: Amy Jordan    972-566-3000      
Principal Investigator: John Nemunaitis, MD         
CTRC @ The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Epp Goodwin    210-450-5798    ctrcreferral@uthscsa.edu   
Principal Investigator: Deva Mahalingam, MD         
Sponsors and Collaborators
Leap Therapeutics, Inc.
Investigators
Study Director: Cyndi Sirard, MD Leap Therapeutics, Inc.
  More Information

Responsible Party: Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02013154     History of Changes
Other Study ID Numbers: DEK-Dkk1-P102  DKN-01  LY2812176 
Study First Received: December 11, 2013
Last Updated: August 25, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016