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

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT01253681

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cancer	Drug: AMG 386, paclitaxel and carboplatin	Phase 1

Detailed Description

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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

Study Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 386, paclitaxel and carboplatin 15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months.	Drug: AMG 386, paclitaxel and carboplatin 15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months.

Arm

Intervention/Treatment

Experimental: AMG 386, paclitaxel and carboplatin

15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months.

Drug: AMG 386, paclitaxel and carboplatin

15 mg/Kg AMG 386 IV (intravenous) weekly plus paclitaxel and carboplatin IV Q3W for 18 weeks, followed by 15mg/Kg AMG 386 IV (intravenous) weekly alone for an additional 18 months.

Outcome Measures

Primary Outcome Measures

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. [18 weeks of combination therapy]

Secondary Outcome Measures

To evaluate the pharmacokinetics (Cmax, AUC and Cmin) of AMG 386 in combination with carboplatin and paclitaxel [Week 1 until Week 7]
To estimate the incidence of anti-AMG 386 antibody formation [Week 1 until maximum of 1 year following first dose]
To evaluate the objective response rate (ORR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel [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 [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 progression-free survival (PFS) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel [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 number of participants with adverse events and clinical laboratory abnormalities [96 weeks]
To evaluate the effect of AMG 386 on the pharmacokinetics (Cmax, AUC and Cmin) of carboplatin and paclitaxel [Week 1 until Week 7]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Footscray	Victoria	Australia	3011
2	Research Site	Malvern	Victoria	Australia	3144
3	Research Site	Parkville	Victoria	Australia	3052
4	Research Site	Brussels		Belgium	1000
5	Research Site	Bruxelles		Belgium	1200
6	Research Site	Leuven		Belgium	3000
7	Research Site	Barcelona	Cataluña	Spain	08035
8	Research Site	Madrid		Spain	28040