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

NCT01253681 | Completed Phase 1

• 1 other identifier: 20090155
• Study Type: interventional
• Target: 27
• Locations: 3 countries
• Sites: 8

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.

Conditions

Carcinoma; Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cancer

Keywords

AMG 386; Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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.

Study Arms (1)

AMG 386, paclitaxel and carboplatin

EXPERIMENTAL

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

Interventions

AMG 386, paclitaxel and carboplatin DRUG

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.

AMG 386, paclitaxel and carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (8)

Research Site

Footscray, Victoria, 3011, Australia

Location

Research Site

Malvern, Victoria, 3144, Australia

Location

Research Site

Parkville, Victoria, 3052, Australia

Location

Research Site

Brussels, 1000, Belgium

Location

Research Site

Brussels, 1200, Belgium

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Barcelona, Catalonia, 08035, Spain

Location

Research Site

Madrid, Madrid, 28040, Spain

Location

Related Publications (1)

• 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.

  PMID: 25037684 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

trebananib; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2010
• First Posted: December 3, 2010
• Study Start: November 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: January 1, 2015
• Last Updated: October 14, 2015

Record last verified: 2015-10

Locations

BE (3); ES (2); AU (3)