Status:

COMPLETED

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

Lead Sponsor:

Leap Therapeutics, Inc.

Conditions:

Endometrial Cancer

Uterine Cancer

Eligibility:

FEMALE

18+ years

Phase:

PHASE2

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 ...

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 ova...

Eligibility Criteria

Inclusion

  • Diagnosis:
  • Epithelial Endometrial Cancer: histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of recurrent previously treated EEC.
  • 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).
  • 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.
  • 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).
  • If prior therapy consisted of palliative chemoradiation therapy, it will be considered one line of therapy.
  • Prior treatment with paclitaxel as part of definitive therapy regimen is acceptable, provided the patient is not intolerant of paclitaxel.
  • Patients who are not eligible to receive paclitaxel will be allowed to receive single agent DKN-01.
  • Tumor tissue for mandatory pre-treatment and on-treatment biopsies.
  • One or more tumors measurable on radiographic imaging as defined by RECIST 1.1.
  • Ambulatory and ≥18 years of age.
  • 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.
  • Estimated life expectancy of at least 3 months, in the judgment of the Investigator.
  • 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.
  • Acceptable liver, renal, hematologic and coagulation function
  • 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.
  • Reliable and willing to make themselves available for the duration of the study and are willing to follow study-specific procedures.
  • Provided written informed consent prior to any study-specific procedures.

Exclusion

  • Patients with the following pure histologies of endometrial or ovarian cancer are not eligible for enrollment: germ cell, sex cord stroma, or sarcoma.
  • New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, or unstable arrhythmia.
  • Fridericia-corrected QT interval (QTcF) \> 470 msec (female) 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 hepatitis C virus ribonucleic acid (HCV RNA) undetected/negative.
  • History of major organ transplant (i.e., heart, lungs, liver, or kidney).
  • History of autologous/allogenic bone marrow transplant.
  • Serious nonmalignant disease
  • Pregnant or nursing.
  • 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.
  • Symptomatic central nervous system (CNS) malignancy or metastasis.
  • Known osteoblastic bony metastasis
  • Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days for nitrosoureas or mitomycin C)
  • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to study entry.
  • 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
  • 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
  • Prior radiation therapy within 14 days prior to study entry
  • Currently receiving any other investigational agent or received an investigational agent within last 30 days of study entry.
  • Previously treated with an anti-DKK1 therapy
  • Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient
  • Active substance abuse

Key Trial Info

Start Date :

March 5 2018

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 27 2021

Estimated Enrollment :

111 Patients enrolled

Trial Details

Trial ID

NCT03395080

Start Date

March 5 2018

End Date

January 27 2021

Last Update

August 1 2025

Active Locations (17)

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Page 1 of 5 (17 locations)

1

University of Alabama

Birmingham, Alabama, United States, 35294

2

HonorHealth

Scottsdale, Arizona, United States, 85258

3

Florida Cancer Specialists & Research Institute

West Palm Beach, Florida, United States, 33401

4

University of Chicago

Chicago, Illinois, United States, 60637