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

NCT ID: NCT03395080

Last Updated: 2025-08-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

111 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-05

Study Completion Date

2021-01-27

Brief Summary

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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

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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)

Conditions

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Endometrial Cancer Uterine Cancer Ovarian Cancer Carcinosarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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DKN-01 monotherapy in recurrent EEC

300mg DKN-01 monotherapy in recurrent EEC

Group Type EXPERIMENTAL

300mg DKN-01

Intervention Type DRUG

Administered by IV infusion

DKN-01+paclitaxel in recurrent EEC

300mg DKN-01+paclitaxel in recurrent EEC

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

Administered by IV infusion

300mg DKN-01

Intervention Type DRUG

Administered by IV infusion

DKN-01 monotherapy in recurrent EOC

300mg DKN-01 monotherapy in recurrent EOC

Group Type EXPERIMENTAL

300mg DKN-01

Intervention Type DRUG

Administered by IV infusion

DKN-01+paclitaxel in recurrent EOC

300mg DKN-01+paclitaxel in recurrent EOC

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

Administered by IV infusion

300mg DKN-01

Intervention Type DRUG

Administered by IV infusion

DKN-01 monotherapy in carcinosarcoma

600mg DKN-01 monotherapy in carcinosarcoma

Group Type EXPERIMENTAL

600mg DKN-01

Intervention Type DRUG

Administered by IV infusion

DKN-01 +paclitaxel in carcinosarcoma

600mg DKN-01 +paclitaxel in carcinosarcoma

Group Type EXPERIMENTAL

Paclitaxel

Intervention Type DRUG

Administered by IV infusion

600mg DKN-01

Intervention Type DRUG

Administered by IV infusion

Interventions

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Paclitaxel

Administered by IV infusion

Intervention Type DRUG

300mg DKN-01

Administered by IV infusion

Intervention Type DRUG

600mg DKN-01

Administered by IV infusion

Intervention Type DRUG

Other Intervention Names

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Taxol

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Leap Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cynthia Sirard

Role: STUDY_DIRECTOR

Leap Therapeutics

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

HonorHealth

Scottsdale, Arizona, United States

Site Status

Florida Cancer Specialists & Research Institute

West Palm Beach, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

HCA Midwest Health System Clinical Research

Kansas City, Missouri, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State University Wexner Medical Center

Hilliard, Ohio, United States

Site Status

Stephenson Cancer Center - University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

The University of Tennessee West Cancer Center

Germantown, Tennessee, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Froedtert and Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Arend R, Dholakia J, Castro C, Matulonis U, Hamilton E, Jackson CG, LyBarger K, Goodman HM, Duska LR, Mahdi H, ElNaggar AC, Kagey MH, Liu A, Piper D, Barroilhet LM, Bradley W, Sachdev J, Sirard CA, O'Malley DM, Birrer M. DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma. Gynecol Oncol. 2023 May;172:82-91. doi: 10.1016/j.ygyno.2023.03.013. Epub 2023 Mar 29.

Reference Type DERIVED
PMID: 37001446 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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DEK-DKK1-P204

Identifier Type: -

Identifier Source: org_study_id

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