Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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.

Tracking Information
First Submitted Date  ICMJE January 2, 2018
First Posted Date  ICMJE January 10, 2018
Last Update Posted Date November 20, 2019
Actual Study Start Date  ICMJE February 5, 2018
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2019)
  • Objective response rate (ORR) in EEC or EEC patients. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • 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) ]
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • The maximum plasma concentration (C max) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • The time taken to reach the maximum plasma concentration (T max) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Area Under the Curved (AUC) will be measured. [ Time Frame: Baseline to study completion (approximately 6 months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
To determine the objective response rate (ORR). [ Time Frame: Baseline to study completion (approximately 6 months) ]
Change History Complete list of historical versions of study NCT03395080 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2019)
  • Objective disease control rate (ODCR) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Overall survival (OS) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Progression-free survival (PFS) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • 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) ]
  • Time to progression (TTP) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Duration of response (DoR) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Duration of complete response (DoCR) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Time to treatment failure (TTTF) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Duration of clinical benefit (DoCB) in patients with recurrent EEC or EOC or Carcinosarcoma (MMMT). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • Overall response rate (ORR) in Carcinosarcoma (MMMT) patients. [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • To determine the objective disease control rate (ODCR). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • To determine overall survival (OS). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • To determine progression-free survival (PFS). [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • To evaluate the adverse drug reactions and toxicities as evaluated by NCI CTCAE, version 4.03 as DKN-01 as monotherapy or in combination with paclitaxel [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • To evaluate additional measures of efficacy, including time to progression (TTP) [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • To evaluate additional measures of efficacy, including duration of response (DoR) [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • To evaluate additional measures of efficacy, including duration of complete response (DoCR) [ Time Frame: Baseline to study completion (approximately 6 months) ]
  • To evaluate additional measures of efficacy, including time to treatment failure (TTTF). [ Time Frame: Baseline to study completion (approximately 6 months) ]
Current Other Pre-specified Outcome Measures
 (submitted: August 10, 2019)
  • 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) ]
  • 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) ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Endometrial Cancer
  • Uterine Cancer
  • Ovarian Cancer
  • Carcinosarcoma
Intervention  ICMJE
  • Drug: Paclitaxel
    Administered by IV infusion
    Other Name: Taxol
  • Drug: 300mg DKN-01
    Administered by IV infusion
  • Drug: 600mg DKN-01
    Administered by IV infusion
Study Arms  ICMJE
  • Experimental: DKN-01 monotherapy in recurrent EEC
    300mg DKN-01 monotherapy in recurrent EEC
    Intervention: Drug: 300mg DKN-01
  • Experimental: DKN-01+paclitaxel in recurrent EEC
    300mg DKN-01+paclitaxel in recurrent EEC
    Interventions:
    • Drug: Paclitaxel
    • Drug: 300mg DKN-01
  • Experimental: DKN-01 monotherapy in recurrent EOC
    300mg DKN-01 monotherapy in recurrent EOC
    Intervention: Drug: 300mg DKN-01
  • Experimental: DKN-01+paclitaxel in recurrent EOC
    300mg DKN-01+paclitaxel in recurrent EOC
    Interventions:
    • Drug: Paclitaxel
    • Drug: 300mg DKN-01
  • Experimental: DKN-01 monotherapy in carcinosarcoma
    600mg DKN-01 monotherapy in carcinosarcoma
    Intervention: Drug: 600mg DKN-01
  • Experimental: DKN-01 +paclitaxel in carcinosarcoma
    600mg DKN-01 +paclitaxel in carcinosarcoma
    Interventions:
    • Drug: Paclitaxel
    • Drug: 600mg DKN-01
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 10, 2019)
124
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2018)
94
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: gender identity
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cynthia Sirard, MD 617-714-0357 csirard@leaptx.com
Contact: Liliana Cygan, MS 617-665-5224 DKNClinicalTrials@leaptx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03395080
Other Study ID Numbers  ICMJE DEK-DKK1-P204
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Leap Therapeutics, Inc.
Study Sponsor  ICMJE Leap Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Cynthia Sirard, MD Leap Therapeutics
Principal Investigator: Rebecca Arend, MD University of Alabama at Birmingham
PRS Account Leap Therapeutics, Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP