Clinical trial NCT01253681: Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With Ovarian Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cancer
Keywords: AMG 386
Ovarian Cancer
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2010-12-03
Enrollment: 27
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: 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.
timeFrame: 18 weeks of combination therapy
Secondary outcomes:
measure: To evaluate the pharmacokinetics (Cmax, AUC and Cmin) of AMG 386 in combination with carboplatin and paclitaxel
timeFrame: Week 1 until Week 7
measure: To estimate the incidence of anti-AMG 386 antibody formation
timeFrame: Week 1 until maximum of 1 year following first dose
measure: To evaluate the objective response rate (ORR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
timeFrame: 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.
measure: To evaluate the duration of response (DOR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
timeFrame: 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.
measure: To evaluate progression-free survival (PFS) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
timeFrame: 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.
measure: To evaluate the number of participants with adverse events and clinical laboratory abnormalities
timeFrame: 96 weeks
measure: To evaluate the effect of AMG 386 on the pharmacokinetics (Cmax, AUC and Cmin) of carboplatin and paclitaxel
timeFrame: Week 1 until Week 7
Other outcomes:
Locations:
city: Footscray
country: Australia
facility: Research Site
state: Victoria
city: Malvern
country: Australia
facility: Research Site
state: Victoria
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Brussels
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: Madrid
country: Spain
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Vergote I, Oaknin A, Baurain JF, Ananda S, Wong S, Su X, Wu B, Zhong Z, Warner D, Casado A. A phase 1b, open-label study of trebananib in combination with paclitaxel and carboplatin in patients with ovarian cancer receiving interval or primary debulking surgery. Eur J Cancer. 2014 Sep;50(14):2408-16. doi: 10.1016/j.ejca.2014.06.010. Epub 2014 Jul 15.