A Phase 3, Randomized, Double-Blind Trial of Weekly Paclitaxel Plus AMG 386 or Placebo in Women With Recurrent Partially Platinum Sensitive or Resistant Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers

Trial Purpose and Description

Trial Purpose

AMG 386 is a first-in-class investigational anti-angiogenic drug that provides potent and

selective inhibition of angiopoietins. AMG 386 is designed to inhibit angiogenesis by sequestering Ang1 and Ang2, thereby preventing their interaction with the Tie2 receptor.  AMG 386 is engineered by fusing truncated human IgG1 Fc domain to 4 copies of a synthetic anti-angiopoietin peptide. The resultant molecule is a nonglycosylated protein, and its biologically active form is a covalently linked homodimer.

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Participation Guidelines

Eligibility Criteria

Inclusion Criteria

Disease Related

• Histologically or cytologically documented invasive epithelial ovarian cancer, primary

peritoneal cancer, or fallopian tube cancer

− Subjects with pseudomyxoma , mesothelioma, unknown primary tumor, sarcoma, or neuroendocrine histology are excluded

− Subjects with borderline ovarian cancer, ie, subjects with low malignant potential tumors, are excluded

− Subjects with clear cell or mucinous histology are excluded

• Subjects must have undergone surgery for ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including at least a unilateral oophorectomy

• Radiographically documented disease progression either on or following the last dose of prior chemotherapy regimen for epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

• Radiologically evaluable disease per RECIST 1.1 with modifications

− There must be radiographically visible tumor

− Subjects with only ascites or pleural effusion are excluded

• Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation therapy, bevacizumab or extended therapy administered after surgical or non-surgical assessment.

− Subjects are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease.

Demographic

• Female 18 years of age or older at the time the written informed consent is obtained

• Subjects of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use an accepted and effective non-hormonal method of contraception [ie, double barrier method (eg, condom plus diaphragm)] from signing the informed consent through 6 months after last dose of study drug.

General

• GOG Performance Status of 0 or 1

• Life expectancy ≥ 3 months (per investigator opinion)

• Subject plans to begin protocol-directed therapy within 7 days from randomization

Laboratory

• Adequate organ and hematological function as evidenced by the following laboratory

studies prior to randomization:

− Hematological function, as follows:

63 Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

− PTT or aPTT ≤ 1.5 x ULN per institutional laboratory range and INR ≤ 1.5

− Renal function, as follows:

≤ 1+ on dipstick, unless quantitative protein is < 1000 mg in a

24-hour urine sample

calculated according to the Cockcroft-Gault formula

Exclusion Criteria

Disease Related

• Subjects who have received more than 3 previous regimens of anti-cancer therapy

for epithelial ovarian, primary peritoneal or fallopian tube cancers

• Subjects who have received paclitaxel as consolidation therapy, maintenance, or

monotherapy are excluded

• Subjects with primary platinum-refractory disease

− Subjects with recurrence or progression during the first 6 cycles or < 6 months after the beginning of the first-line platinum-based chemotherapy are excluded

• Subjects with platinum-free interval (PFI) > 12 months from their last platinum-based

therapy

 • Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from

all radiotherapy-related toxicities

− If all sites of disease have been irradiated, documented progression must have occurred in at least 1 site of disease subsequent to the radiation therapy

• Previous abdominal or pelvic radiotherapy

• History of arterial or venous thromboembolism within 12 months prior to randomization

• History of clinically significant bleeding within 6 months prior to randomization

• History of central nervous system metastasis

Medications

• Has not yet completed a 21 day washout period prior to randomization for any previous anti-cancer systemic therapies (30 days for prior bevacizumab)

• Enrolled in or has not yet completed at least 30 days (prior to randomization) since ending other investigational device or drug, or currently receiving other investigational treatments

• Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 ≥ Grade 2 in severity except alopecia

• Known active or ongoing infection (except uncomplicated urinary tract infection [UTI])

within 14 days prior to randomization

• Currently or previously treated with AMG 386, or other molecules that inhibit the

angiopoietins or Tie2 receptor

Sponsor:

Amgen, Inc

Dates:

November 2011

Last Updated:

Study HIC#:

1009007411

Clinicaltrials.gov ID: Yale3202892