A Study of Demcizumab Plus Paclitaxel in Subjects With Platinum Resistant Ovarian

Study Overview
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Brief Summary
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This is a Phase 1b/2 study of paclitaxel plus demcizumab in subjects with platinum resistant ovarian, primary peritoneal or fallopian tube cancer.

Detailed Description
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Phase 1b portion was completed; Phase 2 portion was not initiated. Subjects must not have received prior weekly paclitaxel or more than 3 prior chemotherapy regimens in the Phase 1b portion of the study and more than 2 prior chemotherapy regimens in the Phase 2 portion of the study. Prior to enrollment, subjects will undergo screening to determine study eligibility. In the Phase 1b portion of study, 3 subjects will be treated at each dose level if no dose-limiting toxicities (DLTs) are observed. If 1 of 3 subjects experiences a DLT, that dose level will be expanded to 6 subjects. If 2 or more subjects experience a DLT, no further subjects will be dosed at that level and 3 additional subjects will be added to the preceding dose cohort unless 6 subjects have already been treated at that dose level. Subjects will be assessed for DLTs from Days 0-28. Dose escalation for newly enrolled subjects, if appropriate, will occur after all subjects in a cohort have completed their Day 28 DLT assessment. After the final patient in the Phase 1b portion of the trial has completed their Day 28 DLT assessment, 50 subjects will be enrolled in the Phase 2 portion of the study and treated with demcizumab at the highest dose level that had < 2 DLTs in the 6 subjects.

Official Title
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SIERRA: A Phase 1b/2 Study of Demcizumab Plus Paclitaxel in Subjects With Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Cancer

Conditions
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Primary Peritoneal Carcinoma

Intervention / Treatment
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* Drug: Demcizumab
* Drug: Taxol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have cytologically or histologically confirmed ovarian, primary peritoneal or fallopian tube cancer.. In addition, subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT, PET-CT or MRI (i.e., RECIST version 1.1 measurable disease). Subjects must have platinum resistant disease (i.e., which is defined as disease progression in less than 6 months after receiving a minimum of 4 cycles of a platinum containing regimen). Subjects with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma N.O.S. Age >21 years ECOG performance status <3 Exclusion Criteria: Subjects receiving any other investigational medicinal product or anti-cancer therapy. Prior therapy with weekly paclitaxel for recurrent disease (administration of weekly paclitaxel as part of an upfront treatment strategy is acceptable as long as the patient had not progressed while receiving weekly paclitaxel or recurred within 4 months of receiving weekly paclitaxel) Non-epithelial ovarian carcinoma, including malignant mixed Mullerian tumors. For the Phase 1b portion of the study, more than 3 prior chemotherapy regimens and for the Phase 2 portion of the study more than 2 prior chemotherapy regimens. Maintenance therapy following induction chemotherapy does not count as a separate regimen. In addition, hormonal therapy (e.g., tamoxifen or an aromatase inhibitor) does not count as a separate regimen. Prior radiotherapy to the pelvis or abdomen Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving lowdose aspirin and/or non-steroidal anti-inflammatory agents.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Demcizumab<br>Demcizumab will be administered prior to paclitaxel by intravenous (IV) infusion. | Drug: Demcizumab<br>* administered intravenously<br>* Other names: OMP-21M18;Drug: Taxol<br>* administered intravenously<br>|
| Experimental: Taxol<br>demcizumab combined with weekly paclitaxel | Drug: Demcizumab<br>* administered intravenously<br>* Other names: OMP-21M18;Drug: Taxol<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Dose limiting toxicities (DLT) of demcizumab when combined with weekly paclitaxel in subjects with platinum resistant ovarian, primary peritoneal or fallopian tube cancer | The maximum tolerated dose (MTD) will be determined in patients treated with demcizumab in combination with weekly paclitaxel | Subjects will be treated and observed for DLT through the end of the first cycle (Days 0-28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of demcizumab when given in combination with weekly paclitaxel | Apparent half life, AUC, clearance, volume of distribution | Plasma sample for Pharmacokinetics (PK) analysis to be obtained prior to the demcizumab infusion on Days 0, 14, 56 and 70 and at the end of the demcizumab infusion (prior to paclitaxel infusion) on Days 0 and 56. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian, Primary Peritoneal, Fallopian Tube Cancer