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A Study of DKN-01 as a Monotherapy or in Combination With Paclitaxel in Patients With Recurrent Epithelial Endometrial or Epithelial Ovarian Cancer or Carcinosarcoma (P204)

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ClinicalTrials.gov Identifier: NCT03395080
Recruitment Status : Recruiting
First Posted : January 10, 2018
Last Update Posted : November 20, 2019
Sponsor:
Information provided by (Responsible Party):
Leap Therapeutics, Inc.

Brief Summary:
A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as a Monotherapy or in Combination with Paclitaxel in Patients With Recurrent Epithelial Endometrial Cancer, Epithelial Ovarian Cancer, or Carcinosarcoma

Condition or disease Intervention/treatment Phase
Endometrial Cancer Uterine Cancer Ovarian Cancer Carcinosarcoma Drug: Paclitaxel Drug: 300mg DKN-01 Drug: 600mg DKN-01 Phase 2

Detailed Description:

This study employs a "basket" design to concurrently investigate DKN-01 as monotherapy and in combination with paclitaxel in patients with recurrent epithelial endometrial cancer (EEC), epithelial ovarian cancer (EOC), or carcinosarcoma (malignant mixed Mullerian tumor [MMMT]. Thus, 6 distinct patient groups are being independently investigated:

  1. 300mg DKN-01 monotherapy in recurrent EEC (Group 1)
  2. 300mg DKN-01+paclitaxel in recurrent EEC (Group 2)
  3. 300mg DKN-01 monotherapy in recurrent EOC (Group 3)
  4. 300mg DKN-01+paclitaxel in recurrent EOC (Group 4)
  5. 600mg DKN-01 monotherapy in recurrent carcinosarcoma (MMMT) (Group 5)
  6. 600mg DKN-01+paclitaxel in recurrent carcinosarcoma (MMMT) (Group 6)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as a Monotherapy or in Combination With Paclitaxel in Patients With Recurrent Epithelial Endometrial, Epithelial Ovarian Cancer, or Carcinosarcoma
Actual Study Start Date : February 5, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Experimental: DKN-01 monotherapy in recurrent EEC
300mg DKN-01 monotherapy in recurrent EEC
Drug: 300mg DKN-01
Administered by IV infusion

Experimental: DKN-01+paclitaxel in recurrent EEC
300mg DKN-01+paclitaxel in recurrent EEC
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol

Drug: 300mg DKN-01
Administered by IV infusion

Experimental: DKN-01 monotherapy in recurrent EOC
300mg DKN-01 monotherapy in recurrent EOC
Drug: 300mg DKN-01
Administered by IV infusion

Experimental: DKN-01+paclitaxel in recurrent EOC
300mg DKN-01+paclitaxel in recurrent EOC
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol

Drug: 300mg DKN-01
Administered by IV infusion

Experimental: DKN-01 monotherapy in carcinosarcoma
600mg DKN-01 monotherapy in carcinosarcoma
Drug: 600mg DKN-01
Administered by IV infusion

Experimental: DKN-01 +paclitaxel in carcinosarcoma
600mg DKN-01 +paclitaxel in carcinosarcoma
Drug: Paclitaxel
Administered by IV infusion
Other Name: Taxol

Drug: 600mg DKN-01
Administered by IV infusion




Primary Outcome Measures :
  1. Objective response rate (ORR) in EEC or EEC patients. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  2. Number of subjects with adverse drug reactions and toxicities as evaluated by NCI CTCAE v5.0 of DKN-01 600 mg ± paclitaxel in patients with recurrent carcinosarcoma (MMMT) in Carcinosarcoma (MMMT) patients. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  3. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Baseline to study completion (approximately 6 months) ]
  4. The maximum plasma concentration (C max) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  5. The time taken to reach the maximum plasma concentration (T max) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  6. Area Under the Curved (AUC) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]

Secondary Outcome Measures :
  1. Objective disease control rate (ODCR) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  2. Overall survival (OS) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  3. Progression-free survival (PFS) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  4. Number of subjects with adverse drug reactions and toxicities as evaluated by NCI CTCAE, version 4.03 as DKN-01 as monotherapy or in combination with paclitaxel in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  5. Time to progression (TTP) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  6. Duration of response (DoR) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  7. Duration of complete response (DoCR) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  8. Time to treatment failure (TTTF) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  9. Duration of clinical benefit (DoCB) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  10. Overall response rate (ORR) in Carcinosarcoma (MMMT) patients. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  11. Concentration of anti-DKN-01 antibodies in human serum in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT) [ Time Frame: Baseline to study completion (approximately 6 months) ]
  12. Number of subjects with adverse drug reactions and toxicities to study treatment regimen in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT) as evaluated by NCI CTCAE v5.0. [ Time Frame: Baseline to study completion (approximately 6 months) ]

Other Outcome Measures:
  1. Number of subjects with response to therapy in patients with and without activating β-catenin mutations and/or Wnt signaling genetic alterations in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT) [ Time Frame: Baseline to study completion (approximately 6 months) ]
  2. Dickkopf-1 (DKK1) concentration in serum and plasma relative to safety and efficacy outcomes in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   gender identity
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis:

    1. Epithelial Endometrial Cancer: histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of recurrent previously treated EEC.
    2. Epithelial Ovarian Cancer: histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of recurrent platinum-resistant/refractory EOC, primary peritoneal, or fallopian tube cancer (i.e., disease recurrence within 6 months of completion of or progression during platinum-based chemotherapy).
    3. Carcinosarcoma/Malignant Mixed Mullerian Tumors: histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of recurrent uterine or ovarian carcinosarcoma (MMMT). Patients must have had only 1 prior chemotherapeutic regimen for management of carcinosarcoma that may have been included chemotherapy (including in adjuvant setting), chemotherapy and radiotherapy, and/or consolidation/maintenance therapy.
  2. Refractory or intolerant to at least one prior standard therapy(ies) for metastatic or locally advanced disease (see Inclusion Criterion #1c for Groups 5-6).

    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 definitive therapy regimen is acceptable, provided the patient is not intolerant of paclitaxel.
    3. Patients who are not eligible to receive paclitaxel will be allowed to receive single agent DKN-01.
  3. Tumor tissue for mandatory pre-treatment and on-treatment biopsies.
  4. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1.
  5. Ambulatory and ≥18 years of age.
  6. ECOG performance status (PS) of 0 or 1

    a. ECOG PS of 2 may be eligible upon the review and approval of the Medical Monitor.

  7. Estimated life expectancy of at least 3 months, in the judgment of the Investigator.
  8. Disease-free of active second/secondary or prior malignancies for ≥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.
  9. Acceptable liver, renal, hematologic and coagulation function
  10. Females of child bearing potential and male partners of female patients must agree to use adequate contraception during the study and for 6 months after their last dose of study drug.
  11. Reliable and willing to make themselves available for the duration of the study and are willing to follow study-specific procedures.
  12. Provided written informed consent prior to any study-specific procedures.

Exclusion Criteria:

  1. Patients with the following pure histologies of endometrial or ovarian cancer are not eligible for enrollment: germ cell, sex cord stroma, or sarcoma.
  2. New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
  3. Fridericia-corrected QT interval (QTcF) > 470 msec (female) or history of congenital long QT syndrome.
  4. Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
  5. Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb), unless hepatitis C virus ribonucleic acid (HCV RNA) undetected/negative.
  6. History of major organ transplant (i.e., heart, lungs, liver, or kidney).
  7. History of autologous/allogenic bone marrow transplant.
  8. Serious nonmalignant disease
  9. Pregnant or nursing.
  10. 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.
  11. Symptomatic central nervous system (CNS) malignancy or metastasis.
  12. Known osteoblastic bony metastasis
  13. Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days for nitrosoureas or mitomycin C)
  14. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to study entry.
  15. 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
  16. History of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil). Patients who exhibit these hypersensitivities will be eligible to receive single agent DKN-01
  17. Prior radiation therapy within 14 days prior to study entry
  18. Currently receiving any other investigational agent or received an investigational agent within last 30 days of study entry.
  19. Previously treated with an anti-DKK1 therapy
  20. Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient
  21. Active substance abuse

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): NCT03395080


Contacts
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Contact: Cynthia Sirard, MD 617-714-0357 csirard@leaptx.com
Contact: Liliana Cygan, MS 617-665-5224 DKNClinicalTrials@leaptx.com

Locations
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United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Contact: Anna Burton, RN    205-934-6454    asb2013@uab.edu   
Contact: Terry Sirles       tsirles@uabmc.edu   
Principal Investigator: Rebecca Arend, MD         
United States, Arizona
HonorHealth Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer, RN MSN AOCNS    480-323-1339    ClinicalTrials@honorhealth.com   
Principal Investigator: Jasgit Sachdev, MD         
United States, Florida
Florida Cancer Specialists & Research Institute Recruiting
West Palm Beach, Florida, United States, 33401
Contact: Jenifer Bar-Nur, RN, BSN    561-472-1696    jbar-nur@flcancer.com   
Principal Investigator: Howard Goodman, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Morgan Whipkey    773-834-0184    mwhipkey@medicine.bsd.uchicago.edu   
Principal Investigator: S. Diane Yamada, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Tina Colella    617-643-5150    TCOLELLA@mgh.harvard.edu   
Principal Investigator: Cesar Castro, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Kathleen McNamara    617-632-3133    KathleenE_McNamara@dfci.harvard.edu   
Sub-Investigator: Ursula Matulonis, MD         
United States, Missouri
HCA Midwest Health System Clinical Research Recruiting
Kansas City, Missouri, United States, 64132
Contact: Karla McNutt, BS    816-276-9698    Karla.mcnutt@hcamidwest.com   
Principal Investigator: Kristopher LyBarger, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Megan Park    216-445-8090    parkm2@ccf.org   
Principal Investigator: Haider Mahdi, MD         
Ohio State University Wexner Medical Center Recruiting
Hilliard, Ohio, United States, 43026
Contact: Molly Myers    614-685-6411    Molly.Myers@osumc.edu   
Principal Investigator: David O'Malley, MD         
United States, Oklahoma
Stephenson Cancer Center - University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Chelsea Baker, MS    405-271-8777 ext 48276    chelsea-baker-1@ouhsc.edu   
Principal Investigator: Camille Gunderson, MD         
United States, Tennessee
The University of Tennessee West Cancer Center Recruiting
Germantown, Tennessee, United States, 38138
Contact: Amanda Fletcher    901-683-0055 ext 61236    afletcher@WESTCLINIC.com   
Principal Investigator: Adam ElNaggar, MD         
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Luke Moore    615-329-7613    luke.moore@sarahcannon.com   
Principal Investigator: Erika P Hamilton, MD         
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Marjorie Wallace    615-322-5092    marjorie.wallace@vumc.org   
Principal Investigator: Marta A Crispens, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Marcella Aguilar    214-648-1479    Marcella.Aguilar@UTSouthwestern.edu   
Principal Investigator: David Miller, MD         
United States, Virginia
University of Virginia Cancer Center Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Anne Gabel    434-982-6657    AM7BD@hscmail.mcc.virginia.edu   
Principal Investigator: Linda Duska, MD         
United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53715
Contact: Claire Kostechka, ACRP-CP    608-263-0796    kostechka@wisc.edu   
Principal Investigator: Lisa Barroilhet, MD         
Froedtert and Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Suki Skandarajah    414-805-5337    sskandarajah@mcw.edu   
Principal Investigator: William Bradley, MD         
Sponsors and Collaborators
Leap Therapeutics, Inc.
Investigators
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Study Director: Cynthia Sirard, MD Leap Therapeutics
Principal Investigator: Rebecca Arend, MD University of Alabama at Birmingham

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Responsible Party: Leap Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03395080     History of Changes
Other Study ID Numbers: DEK-DKK1-P204
First Posted: January 10, 2018    Key Record Dates
Last Update Posted: November 20, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Leap Therapeutics, Inc.:
epithelial histology
Wnt pathway
DKK1
endometrial
uterine
ovarian
carcinosarcoma
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endometrial Neoplasms
Uterine Neoplasms
Carcinosarcoma
Mixed Tumor, Mullerian
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Uterine Diseases
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Connective and Soft Tissue
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators