Trial record 2 of 3 for:    LY2812176

A Study of DKN-01 in Combination With Paclitaxel

This study is currently recruiting participants.
Verified April 2014 by Dekkun Corporation
Sponsor:
Information provided by (Responsible Party):
Dekkun Corporation
ClinicalTrials.gov Identifier:
NCT02013154
First received: December 11, 2013
Last updated: April 3, 2014
Last verified: April 2014
  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
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 Two Part, Phase 1, Multi-Center, Open-Label Study of DKN-01 in Combination With Weekly Paclitaxel in Patients With Relapsed or Refractory Esophageal Cancer or Gastro-Esophageal Junction Tumors

Resource links provided by NLM:


Further study details as provided by Dekkun Corporation:

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: 32
Study Start Date: January 2014
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (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 before Paclitaxel
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 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 before Paclitaxel
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol

Detailed Description:

Part A is a Dose-Escalation Study in Participants with Relapsed or Refractory Esophageal Cancer or Gastro-Esophageal Junction Tumors. Part B is an Expansion Cohort in Participants with Relapsed or Refractory Esophageal Cancer or Gastro-Esophageal Junction Tumors

  Eligibility

Ages Eligible for Study:   30 Years and older
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 whose tumors express Dkk-1 by immunohistochemistry (IHC)
    • 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 provided the patient is not intolerant of paclitaxel
  • Must have one or more tumors measurable on radiographic imaging as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
  • 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 with 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 warfarin: 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 6months, 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
  • 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)
  • 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 registration
  • Known osteoblastic bony metastasis. Screening of asymptomatic participants without a history of metastatic bony lesions is not required
  • Treatment with surgery or chemotherapy within 28 days prior to study entry (42 days for nitrosoureas or mitomycin C)
  • Participants who are currently receiving any other investigational agent or have received an investigational agent within last 30 days 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)
  • Significant allergy to a pharmaceutical therapy that, in the opinion of the investigator, poses an increased risk to the participant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT02013154

Contacts
Contact: Dekkun Corporation Dekkun@Choruspharma.com

Locations
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Janet Murphy, MD         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Not yet recruiting
New Brunswick, New Jersey, United States, 08903
Principal Investigator: Rebecca Moss, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Principal Investigator: Balazs Halmos, MD         
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27710
Principal Investigator: John Strickler, MD         
United States, Tennessee
Tennessee Oncology / Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: Johanna Bendell, MD         
Vanderbilt University / VICC Not yet recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Jordan Berlin, MD         
United States, Texas
CTRC @ The University of Texas Health Science Center at San Antonio Not yet recruiting
San Antonio, Texas, United States, 78229
Principal Investigator: Deva Mahalingam, MD         
United States, Virginia
VCU Massey Cancer Center Not yet recruiting
Richmond, Virginia, United States, 23298
Principal Investigator: Andrew Poklepovic, MD         
Sponsors and Collaborators
Dekkun Corporation
Investigators
Study Director: Email Dekkun@Choruspharma.com Dekkun Corporation
  More Information

No publications provided

Responsible Party: Dekkun Corporation
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: April 3, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 15, 2014