Trial record 1 of 3 for:    LY2812176
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A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dekkun Corporation
ClinicalTrials.gov Identifier:
NCT01457417
First received: October 18, 2011
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

The purpose of this trial is to characterize the safety and toxicity of DKN-01 by determining a maximum-tolerated dose and associated dose limiting toxicity. To evaluate the pharmacodynamic response in patients with cancer. To characterize the pharmacokinetic parameters of DKN-01 in cancer patients who are intolerant to standard/approved therapies.


Condition Intervention Phase
Multiple Myeloma
Solid Tumors
Non-Small Cell Lung Cancer
Drug: DKN-01
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two Part, Phase 1, Multicenter, Open-label Study of DKN-01 Given Intravenously. Part A: A Dose-Escalation Study in Patients With Multiple Myeloma or Advanced Solid Tumors. Part B: An Expansion Cohort in Patients With Relapsed or Refractory Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Dekkun Corporation:

Primary Outcome Measures:
  • Number of participants with clinically significant effects [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: Yes ]
    For both Parts A and B

  • Progression free survival (PFS) in patients with relapsed or refractory NSCLC [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
    For Part B only


Secondary Outcome Measures:
  • Pharmacokinetics: area under the concentration - time curve (AUC) of DKN-01 [ Time Frame: Cycle 1 Day 22 Pre-dose thru Cycle 2 Day 1 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacokinetic: maximum plasma concentration (Cmax) of DKN-01 [ Time Frame: Cycle 1 Day 22 Pre-dose thru Cycle 2 Day 1 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Carboxy-terminal Telopeptide of Type I Collagen (ICTP) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Tartrate-resistant Acid Phosphatase Isoform-5b (TRACP-5b) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Bone Alkaline Phosphatase (bALP) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Osteocalcin/Osteoclast (OC) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Procollagen Type-I N-Propeptide (PINP) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Change in serum Interleukin 6 (IL-6) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Change in serum soluble receptor activator of nuclear factor Kappa B ligand (sRANKL) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Change in serum osteoprotegerin (OPG) [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 1 Day 15 Pre-dose, Cycle 2 Day 1 Pre-dose, Cycle 2 Day 15 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Change in whole blood beta-catenin [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 2 Day 1 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Pharmacodynamics: Change in whole blood survivin [ Time Frame: Cycle 1 Day 1 Pre-dose, Cycle 2 Day 1 Pre-dose ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Progression Free Survival (PFS) in patients who are refractory or intolerant to standard/approved therapies [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Objective Response Rate (ORR) in patients who are refractory or intolerant to standard/approved therapies [ Time Frame: Baseline to study completeion (approximately 3 months) ] [ Designated as safety issue: No ]
    For both Parts A and B

  • Overall Survival (OS) in patients with relapsed or refractory NSCLC [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
    For Part B only

  • Objective Response Rate (ORR) in patients with relapsed or refractory NSCLC [ Time Frame: Baseline to study completion (approximately 3 months) ] [ Designated as safety issue: No ]
    For Part B only


Enrollment: 39
Study Start Date: October 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 75 milligram (mg) DKN-01 Drug: DKN-01
DKN-01 will be administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) are met or the highest planned dose study group is completed. Cycle 1 will define the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. PART B - Dose Confirmation: Once the MTD has been established or the highest planned dose level is completed, 300 mg of DKN-01 will be administered as IV on days 1 and 15 of every 28 day cycle.
Experimental: 150 mg DKN-01 Drug: DKN-01
DKN-01 will be administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) are met or the highest planned dose study group is completed. Cycle 1 will define the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. PART B - Dose Confirmation: Once the MTD has been established or the highest planned dose level is completed, 300 mg of DKN-01 will be administered as IV on days 1 and 15 of every 28 day cycle.
Experimental: 300 mg DKN-01 Drug: DKN-01
DKN-01 will be administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) are met or the highest planned dose study group is completed. Cycle 1 will define the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. PART B - Dose Confirmation: Once the MTD has been established or the highest planned dose level is completed, 300 mg of DKN-01 will be administered as IV on days 1 and 15 of every 28 day cycle.
Experimental: 600 mg DKN-01 Drug: DKN-01
DKN-01 will be administered intravenously (IV) once a week over a minimum of 30 minutes and up to a maximum of 2 hours for dose levels of 75 mg, 150 mg and 300 mg. At the 600 mg dose level, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants will be treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation will occur sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) are met or the highest planned dose study group is completed. Cycle 1 will define the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method will be guided by the incidence of DLTs during the first cycle. PART B - Dose Confirmation: Once the MTD has been established or the highest planned dose level is completed, 300 mg of DKN-01 will be administered as IV on days 1 and 15 of every 28 day cycle.

Detailed Description:

Part A of this trial consists of 4 treatment arms of DKN-01. It is a dose escalation study in patients with multiple myeloma or advanced solid tumors. Patients must be refractory or intolerant to all standard/approved therapy(ies). At each dose level, 3 subjects will be treated. If none of the 3 subjects develop a dose limiting toxicity after a minimum of 4 weeks of treatment, subsequent dose escalation will proceed according to the same schedule. Part B consists of dose confirmation in patients with NSCLC. Patients must be refractory or intolerant to all standard/approved therapy(ies). Approximately 15 patients may be enrolled in Part B.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Part A Only: Patients with histological or cytological confirmed multiple myeloma or advanced solid tumors. For multiple myeloma, patients must have symptomatic myeloma as defined by the International Myeloma Working Group inclusive of measurable serum and/or urine monoclonal protein (M-protein) or for those patients without elevations they must have measurable increased concentrations of free light chains
  • Part B Only: Patients with previously treated, histologically confirmed advanced NSCLC with progressive disease requiring therapy
  • Parts A and B as follows:
  • Patients must be refractory or intolerant to all standard/approved therapy(ies)
  • Patients with solid tumors must have one or more metastatic tumors measurable on computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • Radiation for symptomatic lesions outside the central nervous system (CNS) must have been completed at least 2 week prior to study enrollment
  • Treated brain metastases will be allowed, provided they are asymptomatic. Patients must be off corticosteroids for at least 2 week prior to study entry
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1
  • Life expectancy of at least 3 months
  • Ambulatory patients greater than or equal to (≥) 30 years of age
  • Signed, Institutional Review Board (IRB) - approved informed consent
  • Females with child bearing potential must have had a negative serum pregnancy test within 7 days of study entry
  • Acceptable liver function:

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

    • Solid tumor patients: Calculated creatinine clearance greater than or equal to (≥) 60 milliliters/per minute (mL/min) using the Cockcroft and Gault Method
    • Multiple myeloma patients: Serum creatinine ≤ 1.5 x ULN and/or a calculated creatinine clearance ≥ 45 mL/min using the Cockcroft and Gault Method
  • Acceptable hematologic status:

    • Granulocyte ≥ 1500 cells/cubic millimeter (cells/mm3)
    • Hemoglobin ≥ 9 grams per deciliter (g/dL)
    • Platelet counts:

      • Solid tumor patients ≥ 100,000 (plt/mm3)
      • Multiple myeloma patients ≥ 75,000 (plt/mm3)
  • Urinalysis:

    • No clinically significant abnormalities
  • Acceptable coagulation status:

    • Prothrombin Time/Partial Thromboplastin Time (PT/PTT) ≤ 1.2 x ULN (unless receiving anticoagulation therapy whereby eligibility will be based upon INR as follows)
    • International Normalization Ratio (INR) ≤ 1.6 (unless receiving anticoagulant therapy)

      • If receiving warfarin; INR ≤ 3.0 and no active bleeding (that is, 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 women 18 months following the last dose of study drug

    • NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) during the study, and women must agree to use adequate contraception prior to study entry and for 18 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
  • Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
  • Serum calcium:

    • For solid tumors only: within institutional normal limits
    • Multiple myeloma: ≤ 11.5 milligrams per deciliter (mg/dL)

Exclusion Criteria:

  • History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on magnetic resonance imaging (MRI) scan that are considered clinically significant or may have an impact on the interpretation of the scan. Degenerative changes of the hip joint are not exclusionary
  • Are unable to tolerate the confinement/noise of an MRI scanner or have any contraindication for MRI, including but not limited to the following:

    • Cardiac pacemakers
    • Prosthetic heart valves
    • Metallic splinters in the eye
    • Ferromagnetic hemostatic clips in the central nervous system or body hemostatic clips
    • Cochlear implants
    • Adhesive transdermal patch, if not removed before scans
  • New York Heart Association Class 3 or 4, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on echocardiogram (ECG)
  • Have Fridericia-corrected QT interval (QTcF) greater than (>) 470 millisecond (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, requiring systemic therapy
  • Pregnant or nursing women
  • Treatment with radiation therapy, surgery, or chemotherapy, within 1 month prior to study entry (6 week for nitrosoureas or Mitomycin C)
  • Previously treated with an anti-DKK-1 therapy
  • Significant allergy to a biological pharmaceutical therapy that, in the opinion of the investigator, poses an increased risk to the patient
  • History of major organ transplant (for example: heart, lungs, liver and kidney)
  • Have had an autologous or allogenic bone marrow transplant
  • Have current acute leukemia
  • Patients diagnosed with colon, prostate, breast or small cell lung cancer
  • Have osteoblastic lesions
  • Have concomitant disease known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism and/or Paget's disease of bone
  • Unwillingness or inability to comply with procedures required in this protocol
  • Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Serious nonmalignant disease (for example: hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
  • Patients 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
  • Patients who are currently receiving lithium chloride (LiCl)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01457417

Locations
United States, Arizona
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, New York
New York Oncology Hematology, P.C.
Albany, New York, United States, 12206
United States, South Carolina
Institute for Translational Oncology Research
Greenville, South Carolina, United States, 29605
United States, Texas
Texas Oncology - Baylor, Charles A. Sammons Center
Dallas, Texas, United States, 75246
Tyler Cancer Center
Tyler, Texas, United States, 75702
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
Virginia Commonwealth University - Massey Cancer Center
Richmond, Virginia, United States, 23298
United States, Washington
Northwest Cancer Specialists
Vancouver, Washington, United States, 98684
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: NCT01457417     History of Changes
Other Study ID Numbers: P100, DEK-DKK1-P100, LY2812176
Study First Received: October 18, 2011
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dekkun Corporation:
Cancer
Oncology

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 16, 2014