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
- 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.
- 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
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)
Trial Phase Phase II
Trial Type Treatment
Leap Therapeutics, Inc.
- Primary ID DEK-DKK1-P204
- Secondary IDs NCI-2018-00786
- Clinicaltrials.gov ID NCT03395080