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

NCT03395080 | Completed Phase 2 Results FDA Drug

• 1 other identifier: DEK-DKK1-P204
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 17

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

Conditions

Endometrial Cancer; Uterine Cancer; Ovarian Cancer; Carcinosarcoma

Keywords

epithelial histology; Wnt pathway; DKK1; endometrial; uterine; ovarian; carcinosarcoma

Outcome Measures

Primary Outcomes (2)

• Number of Subjects With Objective Response Rate (ORR) in EEC or EOC Patients

  Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1)

  Baseline to study completion (approximately 6 months)

• Number of Subjects With Objective Response Rate (ORR) in Carcinosarcoma (MMMT) Patients

  Best overall response of Complete Response (CR; disappearance of all target lesions, any pathological lymph nodes whether target or non-target must have reduction in short axis to \<10mm) or Partial Response (PR; at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1)

  Baseline to study completion (approximately 6 months)

Secondary Outcomes (6)

• Number of Subjects With Objective Disease Control Rate (ODCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

  Baseline to study completion (approximately 6 months)

• Overall Survival (OS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

  Baseline to study completion (maximum 17.6 months)

• Progression-free Survival (PFS) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

  Baseline to study completion (maximum 7.1 months)

• Duration of Response (DoR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

  Baseline to study completion (approximately 11 months)

• Duration of Complete Response (DoCR) in Patients With Recurrent EEC or EOC or Carcinosarcoma (MMMT).

  Baseline to study completion (approximately 11 months)

Other Outcomes (10)

• 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)

  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).

  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

  Baseline to study completion (approximately 6 months)

Study Arms (6)

DKN-01 monotherapy in recurrent EEC

EXPERIMENTAL

300mg DKN-01 monotherapy in recurrent EEC

Drug: 300mg DKN-01

DKN-01+paclitaxel in recurrent EEC

EXPERIMENTAL

300mg DKN-01+paclitaxel in recurrent EEC

Drug: Paclitaxel; Drug: 300mg DKN-01

DKN-01 monotherapy in recurrent EOC

EXPERIMENTAL

300mg DKN-01 monotherapy in recurrent EOC

Drug: 300mg DKN-01

DKN-01+paclitaxel in recurrent EOC

EXPERIMENTAL

300mg DKN-01+paclitaxel in recurrent EOC

Drug: Paclitaxel; Drug: 300mg DKN-01

DKN-01 monotherapy in carcinosarcoma

EXPERIMENTAL

600mg DKN-01 monotherapy in carcinosarcoma

Drug: 600mg DKN-01

DKN-01 +paclitaxel in carcinosarcoma

EXPERIMENTAL

600mg DKN-01 +paclitaxel in carcinosarcoma

Drug: Paclitaxel; Drug: 600mg DKN-01

Interventions

Paclitaxel DRUG

Administered by IV infusion

Also known as: Taxol

DKN-01 +paclitaxel in carcinosarcoma; DKN-01+paclitaxel in recurrent EEC; DKN-01+paclitaxel in recurrent EOC

300mg DKN-01 DRUG

Administered by IV infusion

DKN-01 monotherapy in recurrent EEC; DKN-01 monotherapy in recurrent EOC; DKN-01+paclitaxel in recurrent EEC; DKN-01+paclitaxel in recurrent EOC

600mg DKN-01 DRUG

Administered by IV infusion

DKN-01 +paclitaxel in carcinosarcoma; DKN-01 monotherapy in carcinosarcoma

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: gender identity
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leap Therapeutics, Inc.: lead

Study Sites (17)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Florida Cancer Specialists & Research Institute

West Palm Beach, Florida, 33401, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

HCA Midwest Health System Clinical Research

Kansas City, Missouri, 64132, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Wexner Medical Center

Hilliard, Ohio, 43026, United States

Location

Stephenson Cancer Center - University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

The University of Tennessee West Cancer Center

Germantown, Tennessee, 38138, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

Location

University of Wisconsin

Madison, Wisconsin, 53715, United States

Location

Froedtert and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 37001446 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Uterine Neoplasms; Ovarian Neoplasms; Carcinosarcoma

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Cynthia Sirard, MD, Chief Medical Officer
• Organization: Leap Therapeutics, Inc.

csirard@leaptx.com

+1-617-714-0360

Study Officials

• Cynthia Sirard

  Leap Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 10, 2018
• Study Start: March 5, 2018
• Primary Completion: September 9, 2020
• Study Completion: January 27, 2021
• Last Updated: August 1, 2025
• Results First Posted: June 9, 2023

Record last verified: 2023-05

Locations

US (17)