A Multi-Center Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With High-Risk Stage I and Stages II-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01253681
• Date of registration: 21/10/2010
• Primary sponsor: Amgen
• Public title: A Multi-Center Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With High-Risk Stage I and Stages II-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers
• Scientific title: A Phase 1b Open-Label, Multi-Center Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With High-Risk Stage I and Stages II-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers
• Date of first enrolment: November 2010
• Target sample size: 25
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT01253681
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Australia, Belgium, Spain

Contacts

• Name: MD
• Affiliation: Amgen

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Carcinoma

Fallopian Tube Cancer

Ovarian Cancer

Primary Peritoneal Cancer

Intervention(s)

Drug: AMG 386, paclitaxel and carboplatin

Primary Outcome(s)

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. [Time Frame: 18 weeks of combination therapy]

Secondary Outcome(s)

To estimate the incidence of anti-AMG 386 antibody formation [Time Frame: Week 1 until maximum of 1 year following first dose]

To evaluate progression-free survival (PFS) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel [Time Frame: From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.]

To evaluate the duration of response (DOR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel [Time Frame: From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.]

To evaluate the effect of AMG 386 on the pharmacokinetics (Cmax, AUC and Cmin) of carboplatin and paclitaxel [Time Frame: Week 1 until Week 7]

To evaluate the number of participants with adverse events and clinical laboratory abnormalities [Time Frame: 96 weeks]

To evaluate the objective response rate (ORR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel [Time Frame: From date of first dose until the subject reaches End of Study. This will continue until 36 months after the last subject has been enrolled.]

To evaluate the pharmacokinetics (Cmax, AUC and Cmin) of AMG 386 in combination with carboplatin and paclitaxel [Time Frame: Week 1 until Week 7]

Secondary ID(s)

20090155

Source(s) of Monetary Support

Please refer to primary and secondary sponsors