Overview

Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With Ovarian Cancer

Status:
Completed
Trial end date:
2015-01-01
Target enrollment:
0
Participant gender:
Female
Summary
To evaluate whether AMG 386 in combination with paclitaxel and carboplatin is safe and well tolerated in the first-line treatment of high-risk stage I and stages II-IV epithelial ovarian, primary peritoneal and fallopian tube cancers. The hypothesis is that AMG 386 in combination with carboplatin and paclitaxel is safe and well tolerated.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Amgen
Treatments:
Albumin-Bound Paclitaxel
Carboplatin
Paclitaxel
Trebananib
Criteria
Inclusion Criteria:

- Female subjects more than 18 years of age with newly diagnosed high-risk FIGO Stage I
(grade 3, or aneuploid grade 1 or 2) or Stages II-IV epithelial ovarian, primary
peritoneal and fallopian tube cancer with an indication for first-line treatment with
paclitaxel and carboplatin x 6 cycles. Subjects with pseudomyxoma, mesothelioma,
adenocarcinoma of unknown primary tumor, sarcoma, or neuroendocrine histology are
excluded.

- Subjects with high-risk stage I, stage II, or stage IIIA-B must have had prior primary
debulking surgery that occurred no less than 4 weeks, and no more than 12 weeks, prior
to enrollment. Subjects must have recovered fully from surgery in the opinion of the
investigator

- Subjects with Stage IIIC or IV disease who have not had primary debulking surgery must
have planned interval debulking surgery following 3 cycles of AMG 386, paclitaxel and
carboplatin

- 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 (i.e, double barrier method (eg, condom
plus diaphragm) from signing the informed consent through 6 months after last dose of
study drug

- 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 enrollment

- Adequate organ and hematological function as evidenced by the following laboratory
studies prior to enrollment:

Hematological function, as follows:

- Hemoglobin ≥ 9 g/dL

- Absolute neutrophil count (ANC) ≥ 1.5 x 10x9/L

- Platelet count ≥ 100 x 10x9/L and ≤ 850 x 10x9/L

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

Renal function, as follows:

- Urinary protein quantitative value of ≤ 30 mg/dL in urinalysis or ≤ 1+ on dipstick,
unless quantitative protein is < 1000 mg in a 24 hour urine sample

- Creatinine clearance > 40 mL/min per 24-hr urine collection or calculated according to
the Cockcroft-Gault formula

Hepatic function, as follows:

- AST and ALT ≤ 2.5 x ULN per institutional laboratory range (or ≤ 5 x ULN if liver
metastases are present)

- Total bilirubin ≤ 1.5x institutions' ULN Nutritional

- Albumin ≥ 2.8 g/dL

Exclusion Criteria:

- Prior use of anticancer therapy or experimental therapy for epithelial ovarian,
primary peritoneal or fallopian tube cancers

- Previous abdominal and/or pelvic external beam radiotherapy

- Subjects believed to be a higher than average risk of bowel perforation. This includes
current symptoms of partial or complete bowel obstruction, recent (within 6 months)
history of fistula or bowel perforation, subjects requiring total parenteral nutrition
and continuous hydration

- History of arterial or venous thromboembolism within 12 months prior to enrollment

- History of clinically significant bleeding within 6 months prior to enrollment

- History of central nervous system metastasis

- Known active or ongoing infection (except uncomplicated urinary tract infection)
within 14 days prior to enrollment

- Currently or previously treated with AMG 386, or other molecules that inhibit the
angiopoietins or Tie2 receptor

- Current or within 30 days prior to enrollment treatment with immune modulators such as
systemic cyclosporine or tacrolimus

- Prior myeloablative high-dose chemotherapy with allogeneic or autologous stem cell (or
bone marrow) transplant

- Clinically significant cardiac disease within 12 months prior to enrollment, including
myocardial infarction, unstable angina, grade 2 or greater peripheral vascular
disease, cerebrovascular accident, transient ischemic attack, congestive heart
failure, or arrhythmias not controlled by outpatient medication or placement of
percutaneous transluminal coronary angioplasty/stent

- Uncontrolled hypertension as defined as diastolic blood pressure > 90 mmHg OR systolic
blood pressure > 140 mmHg. The use of anti-hypertensive medications to control
hypertension is permitted

- Subjects with a history of prior malignancy, except:

Malignancy treated with curative intent and with no known active disease present for ≥ 3
years prior to enrollment and felt to be at low risk for recurrence by treating physician,
Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of
disease Adequately treated cervical carcinoma in situ without evidence of disease

- Major surgery within 28 days prior to enrollment or still recovering from prior
surgery

- Minor surgical procedures, including placement of tunneled central venous access
device, within 3 days prior to enrollment

- History of allergic reactions to bacterially-produced proteins

- Hypersensitivity to paclitaxel or drugs using the vehicle cremophor

- Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding or
planning to become pregnant within 6 months after the end of treatment

- Subject has known positive test(s) for human immunodeficiency virus (HIV) infection,
hepatitis C virus, acute or chronic active hepatitis B infection

- Any condition which in the investigator's opinion makes the subject unsuitable for
study participation

- Any uncontrolled concurrent illness or history of any medical condition that may
interfere with the interpretation of the study results

- Non-healing wound, ulcer (including gastrointestinal) or fracture

- Subject has previously been enrolled onto this study

- Subject will not be available for follow-up assessment

- Subject has known sensitivity to any of the products to be administered during dosing

- Subject has any kind of disorder that compromises the ability of the subject to give
written informed consent and/or to comply with study procedures