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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01253681




Registration number
NCT01253681
Ethics application status
Date submitted
21/10/2010
Date registered
3/12/2010
Date last updated
14/10/2015

Titles & IDs
Public title
Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With Ovarian Cancer
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
Secondary ID [1] 0 0
20090155
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma 0 0
Fallopian Tube Cancer 0 0
Ovarian Cancer 0 0
Primary Peritoneal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 386, paclitaxel and carboplatin

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.


Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
18 weeks of combination therapy
Secondary outcome [1] 0 0
To evaluate the pharmacokinetics (Cmax, AUC and Cmin) of AMG 386 in combination with carboplatin and paclitaxel
Timepoint [1] 0 0
Week 1 until Week 7
Secondary outcome [2] 0 0
To estimate the incidence of anti-AMG 386 antibody formation
Timepoint [2] 0 0
Week 1 until maximum of 1 year following first dose
Secondary outcome [3] 0 0
To evaluate the objective response rate (ORR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
To evaluate the duration of response (DOR) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
To evaluate progression-free survival (PFS) among subjects receiving AMG 386 in combination with carboplatin and paclitaxel
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
To evaluate the number of participants with adverse events and clinical laboratory abnormalities
Timepoint [6] 0 0
96 weeks
Secondary outcome [7] 0 0
To evaluate the effect of AMG 386 on the pharmacokinetics (Cmax, AUC and Cmin) of carboplatin and paclitaxel
Timepoint [7] 0 0
Week 1 until Week 7

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Research Site - Footscray
Recruitment hospital [2] 0 0
Research Site - Malvern
Recruitment hospital [3] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
3011 - Footscray
Recruitment postcode(s) [2] 0 0
3144 - Malvern
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Spain
State/province [4] 0 0
Cataluña
Country [5] 0 0
Spain
State/province [5] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01253681
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications