A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors

NCT01457417 | Completed Phase 1 Results

• 3 other identifiers: P100DEK-DKK1-P100LY2812176
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Multiple Myeloma; Solid Tumors; Non-Small Cell Lung Cancer

Keywords

Cancer; Oncology

Outcome Measures

Primary Outcomes (3)

• Summary of Total Adverse Events (AE)

  Total Adverse Events (AE), total treatment emergent adverse events (TEAE), total Serious Adverse Events (SAE), and total dose-limiting toxicity (DLT) for both Parts A and B.

  Baseline to study completion (approximately 3 months)

• Summary of Patients With Adverse Events (AE)

  Number of patients who had Adverse Events (AE) including treatment related treatment emergent adverse events (TEAE), Common Toxicity Criteria for Adverse Effects (CTCAE), and Serious Adverse Events (SAE) for both Parts A and B. Severity was coded to NCI CTCAE version 4.02. For maximum severity and relationship, patients were counted only once in the most severe or most related category.

  Baseline to study completion (approximately 3 months)

• Progression Free Survival (PFS) in Patients With Relapsed or Refractory Non-small Cell Lung Cancer (NSCLC)

  For Part B only. The distribution of PFS was estimated using the Kaplan-Meier (KM) method. PFS was defined as the time from the date of signed informed consent to the first date of objectively determined progressive disease (Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and International Multiple Myeloma Working Group (IMWG)) or death from any cause. For patients who were still alive at the time of analysis (ie, data cut-off date) and without evidence of tumor progression, PFS was censored at the date of the most recent objective progression-free observation.

  Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause

Secondary Outcomes (8)

• Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01

  Cycle 1 Day 1 (first dose, all groups)

• Pharmacokinetics: Area Under the Concentration - Time Curve (AUC) of DKN-01

  Cycle 1 Day 22 (Fourth Dose for QW)

• Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01

  Cycle 1 Day 1 (first dose, all groups)

• Pharmacokinetic: Maximum Plasma Concentration (Cmax) of DKN-01

  Cycle 1 Day 22 (Fourth dose for QW groups)

• Progression Free Survival (PFS) in Patients Who Are Refractory or Intolerant to Standard/Approved Therapies

  Time from the date of signed informed consent to the first date of objectively determined progressive disease or death from any cause

Study Arms (5)

75 milligram (mg) DKN-01 Part A

EXPERIMENTAL

DKN-01: DKN-01 was 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 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.

Drug: DKN-01

150 mg DKN-01 Part A

EXPERIMENTAL

DKN-01: DKN-01 was 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 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.

Drug: DKN-01

300 mg DKN-01 Part A

EXPERIMENTAL

DKN-01: DKN-01 was 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 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.

Drug: DKN-01

600 mg DKN-01 Part A

EXPERIMENTAL

DKN-01: DKN-01 was 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 was administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: Study group of 3 participants were treated with a 28 day cycle of DKN-01 at an assigned dose level until disease progression. Dose escalation occurred sequentially over the doses of 75, 150, 300, and 600 mg until the criteria for reaching the maximum tolerated dose (MTD) were met or the highest planned dose study group was completed. Cycle 1 defined the dose limiting toxicity (DLT) period that governs dose escalation. The dose escalation method was guided by the incidence of DLTs during the first cycle.

Drug: DKN-01

300 mg DKN-01 Part B

EXPERIMENTAL

Dose Confirmation: Once the MTD had been established or the highest planned dose level completed, 300 mg of DKN-01 was administered as IV on days 1 and 15 of every 28 day cycle.

Drug: DKN-01

Interventions

DKN-01 DRUG

DKN-01 will be administered intravenously (IV) once a week over 30 minutes (min) and 2 hours (max) for 75, 150 and 300 mg. At 600 mg, DKN-01 will be administered by IV on days 1 and 15 of each cycle. PART A - Dose Escalation: 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 maximum tolerated dose (MTD) are met (or highest planned dose study group is completed). Cycle 1 will define the dose limiting toxicity (DLT) that governs dose escalation. PART B - Dose Confirmation: Once the MTD is established (or the highest planned dose level), 300 mg of DKN-01 will be administered IV on days 1 and 15 of every 28 day cycle.

Also known as: Formerly LY2812176

150 mg DKN-01 Part A; 300 mg DKN-01 Part A; 300 mg DKN-01 Part B; 600 mg DKN-01 Part A; 75 milligram (mg) DKN-01 Part A

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part A: Patients with histological or cytological confirmed multiple myeloma or advanced solid tumors. For multiple myeloma, 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 without elevations they must have measurable increased concentrations of free light chains
• Part B: Patients with previously treated, histologically confirmed advanced NSCLC with progressive disease requiring therapy
• Parts A and B:
• 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, if 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
• Females with child bearing potential must have a negative serum pregnancy test within 7 days of study entry
• Acceptable liver function, renal function, hematologic status
• Urinalysis - No clinically significant abnormalities
• Acceptable coagulation status:
• Prothrombin Time/Partial Thromboplastin Time (PT/PTT) ≤ 1.2 x upper limit of normal (ULN) (unless receiving anticoagulation therapy - eligibility based upon INR)

You may not qualify if:

• Unable to tolerate the confinement/noise of an MRI scanner or have any contraindication for MRI
• New York Heart Association Class 3 or 4, cardiac disease, myocardial infarction, unstable arrhythmia, or evidence of ischemia
• Have Fridericia-corrected QT interval (QTcF) \> 470 millisecond (msec) (female) or \> 450 (male), or history of congenital long QT syndrome.
• Active, uncontrolled bacterial, viral, or fungal infections
• Pregnant or nursing women
• Radiation therapy, surgery, or chemotherapy, within 1 month prior to study entry
• Previously treated with an anti-Dickkopf-related protein 1 (DKK-1) therapy
• Significant allergy to a biological pharmaceutical therapy
• History of major organ transplant
• Had an autologous or allogenic bone marrow transplant, current acute leukemia, colon, prostate, breast or small cell lung cancer, osteoblastic lesions, concomitant disease known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism and/or Paget's disease of bone
• Unwillingness / inability to comply with procedures
• Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Serious nonmalignant disease
• Receiving other investigational agent or have received other investigational agent within last 30 days or 5 half-lives, whichever is longer
• Receiving lithium chloride (LiCl)

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead

Study Sites (8)

Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

Location

Greenville Hospital System University Medical Center

Greenville, South Carolina, 29605, United States

Location

Texas Oncology - Baylor, Charles A. Sammonds Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

Virginia Oncology Associated

Norfolk, Virginia, 23502, United States

Location

Virginia Commonwealth University - Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Carcinoma, Non-Small-Cell Lung; Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Cynthia Sirard, MD
• Organization: Healthcare Pharmaceuticals, Inc

CSirard@hcven.com

617-714-0357

Study Officials

• Cyndi Sirard, MD

  Heatlhcare Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: October 24, 2011
• Study Start: January 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: September 28, 2016
• Results First Posted: September 28, 2016

Record last verified: 2016-09

Locations

US (8)