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Trial record 3 of 4 for:    LY2812176

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 : September 18, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Leap Therapeutics, Inc.

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

Condition or disease Intervention/treatment Phase
Esophageal Neoplasms Adenocarcinoma of the Gastroesophageal Junction Gastroesophageal Cancer Squamous Cell Carcinoma Gastric Adenocarcinoma Drug: DKN-01 Drug: Paclitaxel Drug: Pembrolizumab Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 224 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2014
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : May 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

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
Drug: DKN-01
Administered by IV infusion

Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol

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
Drug: DKN-01
Administered by IV infusion

Drug: Pembrolizumab
Administered by IV infusion
Other Name: Keytruda




Primary Outcome Measures :
  1. 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) ]
  2. 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 ]

Secondary Outcome Measures :
  1. Clinical response to treatment [ Time Frame: Baseline to study completion (approximately 3 months) ]
  2. Objective Response Rate (ORR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  3. Objective Disease Control Rate (ODCR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  4. Duration of Response (DoR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  5. Duration of CR (DoCR) [ Time Frame: Baseline to study completion (approximately 3 months) ]
  6. Overall Survival (OS) [ Time Frame: Baseline to study completion (approximately 3 months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02013154


Contacts
Contact: Cyndi Sirard csirard@leaptx.com

Locations
United States, California
Cedars Sinai Medical Care Foundation Recruiting
Los Angeles, California, United States, 90025
Contact: Teresa Mata    310-231-2115    tmata@theangelesclinic.org   
Contact: Saba Mukarram    310-231-2181    smukarram@theangelesclinic.org   
Principal Investigator: Samuel Klempner, MD         
United States, Connecticut
Smilow Cancer Hospital at Yale - New Haven Recruiting
New Haven, Connecticut, United States, 06520
Contact: Kirsten Dooley    203-836-4156    kirsten.dooley@yale.edu   
Contact: Thomas Bouchard    203-785-7043    Thomas.Bouchard@yale.edu   
Principal Investigator: Stacey Stein, MD         
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Rita Staples    312-695-0703    rita.staples@northwestern.edu   
Principal Investigator: Victoria Villaflor, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: GI Research Line    617-632-5960      
Contact: Samantha Schuetz    617-632-5575    SamanthaR_Schuetz@dfci.harvard.edu   
Principal Investigator: Peter Enzinger, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Anthony Afflitto    617-724-1990    aafflitto@mgh.harvard.edu   
Principal Investigator: Jeffrey Clark, MD         
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: Leighanne Hartman    919-668-1861    leighanne.hartman@duke.edu   
Contact: Anthony Amara    919.668.1861    Anthony.amara@duke.edu   
Principal Investigator: John Strickler, MD         
United States, Tennessee
Tennessee Oncology / Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Rita Baker    615-686-7467    rita.baker@sarahcannon.com   
Contact: Elias King    615-329-7645    Steven.King2@SarahCannon.com   
Principal Investigator: Johanna Bendell, MD         
Vanderbilt University / VICC Recruiting
Nashville, Tennessee, United States, 37232
Contact: Research Phone Number    800-811-8480      
Contact: Vicky Stephens    615-936-5869    vicki.stephens@vanderbilt.edu   
Principal Investigator: Laura Goff, MD         
United States, Texas
Mary Crowley Cancer Center Recruiting
Dallas, Texas, United States, 75251
Contact: Noureen Karimi    214-658-1985    NKarimi@MaryCrowley.Org   
Principal Investigator: James Strauss, MD         
CTRC @ The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Epp Goodwin       ctrcreferral@uthscsa.edu   
Contact: Jennifer Moseley    210-450-1799    moseleyj@uthscsa.edu   
Principal Investigator: Laura Tenner, MD         
Sponsors and Collaborators
Leap Therapeutics, Inc.
Merck Sharp & Dohme Corp.
Investigators
Study Director: Cyndi Sirard, MD Leap Therapeutics, Inc.

Responsible Party: Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02013154     History of Changes
Other Study ID Numbers: DEK-DKK1-P102
DKN-01
LY2812176
First Posted: December 17, 2013    Key Record Dates
Last Update Posted: September 18, 2018
Last Verified: September 2018

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
Pembrolizumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action