- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00479817
Phase 2 AMG 386 in Comb. Paclitaxel for Subjects With Advanced Recurrent Epithelial Ovarian or Primary Peritoneal Cancer
A Randomized, Double-Blind, Placebo Controlled, Phase 2 Trial of Paclitaxel in Combination With AMG 386 in Subjects With Advanced Recurrent Epithelial Ovarian or Primary Peritoneal Cancer
This study is a phase 2, randomized, double-blind, placebo controlled, multi-center study to estimate the improvement in PFS (compared to control subjects) and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel in the treatment of subjects with advanced recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Primary Outcome Measure:
• Progression free survival (PFS)
Secondary Outcome Measures:
- Object Response Rate (ORR), duration of response (DOR). CA-125 response rate
- Safety and Tolerability
- Change and duration of change on blood levels of CA-125
Study Overview
Status
Intervention / Treatment
Detailed Description
Primary Objective:
To estimate the treatment effect as measured by progression free survival (PFS) of subjects with recurrent ovarian cancer receiving AMG 386 (either 3 mg/kg or 10 mg/kg IV QW) in combination with paclitaxel (80 mg/m2 IV QW; 3 on/1 off)compared to subjects receiving paclitaxel (80 mg/m2 IV QW; 3 on/1 off) plus placebo
Secondary Objective(s):
- To evaluate the safety and tolerability of the combination regimen of AMG 386/paclitaxel
- To estimate other measures of treatment effect (by parameters other than PFS) of subjects receiving AMG 386 in combination with paclitaxel compared to subjects receiving paclitaxel plus placebo
- To evaluate the AMG 386 pharmacokinetics parameters (Cmax and Cmin ) when administered with paclitaxel in subjects with recurrent ovarian cancer
- To estimate the incidence of occurrence of anti-AMG 386 antibody formation
- To estimate the change and duration of change on blood levels of CA-125
- To evaluate the clinical benefit among subjects receiving AMG 386 10 mg/kg monotherapy after disease progression on paclitaxel
- To estimate the impact of AMG 386 on patient reported ovarian cancer specific symptoms and HRQoL using the FACT-O, the FACT-O ovarian cancer subscale (OCS), and the FACT-O 3-item (O1, O2, O3) cancer symptom specific subscale (OCS 3-item subscale)
Exploratory Objective(s):
- To explore the associations between progression free survival, objective response, CA-125, and continuous measures of tumor burden (the percentage change from baseline in the sum of the longest diameters of target lesions)
- To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, CA-125 and other markers
- To investigate the effects of genetic variation in drug metabolism, cancer genes and drug target genes on ovarian cancer and subject response to investigational product (separate informed consent)
- To explore the impact of AMG 386 on patient reported overall health status as measured by the EuroQoL (EQ-5D)
Hypothesis:
This study will provide an estimate and corresponding 2-sided 80% confidence interval with an approximate maximum half-width of 0.22 of the efficacy, as measured by the PFS hazard ratio of AMG 386 in combination with paclitaxel versus paclitaxel alone for 2 pooled dose groups of AMG 386 (10 mg/kg QW and 3 mg/kg QW) in combination with paclitaxel versus the paclitaxel plus placebo group.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
In. Criteria -Subjects must have histologically or cytologically documented epithelial ovarian (FIGO Stage II-IV), fallopian tube or primary peritoneal cancer.
(Subjects with pseudomyxoma or mesothelioma are excluded)
- Radiographically documented progression per RECIST criteria with modifications or progression of CA-125 as defined by the Rustin during or subsequent to the last chemotherapy regimen.
- May include measurable or non-measurable disease
- All scans and x-rays used to document measurable or non-measurable disease must be done within 3 weeks (21 days) of enrollment.
- No more than 3 previous regimens of anti-cancer therapy. Subjects must have received at least one platinum containing regimen
- 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 use an accepted and effective non-hormonal method of contraception (ie, double barrier method (eg, condom plus diaphragm)) from signing the informed consent through 6 months after last dose of study drug.
Laboratory
- Adequate organ and hematological function as evidenced by the following laboratory studies within 2 weeks (14 days) of randomization:
- Hematological function, as follows:
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L and ≤ 850 x 109/L Hemoglobin ≥ 9 g/dL PTT or aPTT≤ 1.5 x ULN per institutional laboratory rand and INR ≤ 1.5 x 109/L per instiutiona laboratory range
Renal function, as follows:
Creatinine ≤ 2.0 mg/dL Calculated creatinine clearance > 40 cc/min according to the Cockcroft-Gault formula
-Hepatic function, as follows: Total bilirubin ≤ 2.0 x ULN SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present) Nutritional
- Albumin ≥ 2.8 mg/dL General
- GOG Performance Status of 0 or 1
- Subject plans to begin protocol directed therapy within 7 days of randomization Ex Criteria
- Subjects believed to be a higher than average risk for bowel perforation. This includes 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
- Known ongoing small bowel dysfunction (ie, persistent nausea, vomiting)
- Radiotherapy ≤ 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities
- If all sites of disease have been irradiated, documented progression must have occurred in at least one site of disease subsequent to the radiation therapy.
- Previous abdominal radiotherapy
- Has not yet completed a 21 day washout period for any previous anti-cancer systemic therapies (60 days for bevacizumab or any molecule of long half-life).
- Enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or is receiving other investigational agent(s)
- Current or prior history of central nervous system metastasis
- Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral neuropathy ≥grade 2
- History of arterial or venous thrombosis within 12 months prior to randomization
- Concurrent or prior (within 1 week before study day 1) anticoagulation therapy, excluding aspirin and anti platelet agents. The concurrent use of low molecular weight heparin or low dose warfarin (ie, ≤ 1 mg daily) for prophylaxis against thrombosis is acceptable while on study
- History of bleeding diathesis or clinically significant bleeding within 14 days of randomization
- Major surgical procedure within 4 weeks (28 days) prior to Study Day 1
- Minor surgical procedure, or placement of central venous access device, within 7 days of Study Day 1
- Paracentesis and/or thoracentesis are permitted prior to and while on study at the discretion of the investigator as clinically indicated. Investigators should document the frequency of paracenteses and/or thoracentesis that occurred prior to the enrollment of the subject in this study on the appropriate eCRFs. Investigators should also document each paracentesis and/or thoracentesis that occurs while a subject is on study on the appropriate eCRFs.
- Subjects with a history of prior malignancy, except:
- Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before 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
- Prior myeloablative high dose chemotherapy with allogeneic or autologous stem cell (or bone marrow) transplant
- Clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
- Non-healing wound, ulcer or fracture
- Ongoing or active infection
- Unacceptable hypersensitivity to paclitaxel or drugs containing cremophor
- Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
- Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820
- Prior therapy against vascular endothelial growth factor or the vascular endothelial growth factor receptors including, but not limited to, bevacizumab, sunitinib, sorafenib, motesanib (AMG 706) or cediranib (AZD-2171), is permitted so long as the agent does not have any known activity against angiopoietin 1 or 2, or the receptors TIE-1 or TIE-2
- Current or within 30 days of randomization treatment with immune modulators such as cyclosporine and tacrolimus
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A
Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 10 mg/kg IV QW
|
10mg/kg
3 mg/kg
Paclitaxel 80 mg/m2 IV QW (3 on/1 off)
|
Experimental: Arm B
Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 3 mg/kg IV QW
|
10mg/kg
3 mg/kg
Paclitaxel 80 mg/m2 IV QW (3 on/1 off)
|
Active Comparator: Arm C
Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 placebo
|
Paclitaxel 80 mg/m2 IV QW (3 on/1 off)
AMG 386 Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression Free Survival
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall Survival
Time Frame: 2 years
|
2 years
|
Duration of Response
Time Frame: 2 years
|
2 years
|
Objective Response Rate
Time Frame: 2 years
|
2 years
|
Time to Progression
Time Frame: 2 years
|
2 years
|
Safety and Tolerability
Time Frame: 2 years
|
2 years
|
Modified RECIST/CA-125 Progression Free Survival
Time Frame: 2 years
|
2 years
|
CA-125 Response Rate
Time Frame: 2 years
|
2 years
|
Estimate of reduction in tumor burden
Time Frame: 2 years
|
2 years
|
Incidence of AEs and significant laboratory changes
Time Frame: 2 years
|
2 years
|
Time to Response
Time Frame: 2 years
|
2 years
|
Change from baseline in blood levels of CA-125
Time Frame: 2 years
|
2 years
|
Time-adjusted area under the curve for PROs
Time Frame: 2 years
|
2 years
|
AMG 386 Pharmacokinetic parameters
Time Frame: 2 years
|
2 years
|
Incidence of the occurence of AMG 386 Antibody formation
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Karlan BY, Oza AM, Richardson GE, Provencher DM, Hansen VL, Buck M, Chambers SK, Ghatage P, Pippitt CH Jr, Brown JV 3rd, Covens A, Nagarkar RV, Davy M, Leath CA 3rd, Nguyen H, Stepan DE, Weinreich DM, Tassoudji M, Sun YN, Vergote IB. Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer. J Clin Oncol. 2012 Feb 1;30(4):362-71. doi: 10.1200/JCO.2010.34.3178. Epub 2011 Dec 19.
- Lu JF, Rasmussen E, Karlan BY, Vergote IB, Navale L, Kuchimanchi M, Melara R, Stepan DE, Weinreich DM, Sun YN. Exposure-response relationship of AMG 386 in combination with weekly paclitaxel in recurrent ovarian cancer and its implication for dose selection. Cancer Chemother Pharmacol. 2012 May;69(5):1135-44. doi: 10.1007/s00280-011-1787-5. Epub 2012 Jan 1.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Peritoneal Diseases
- Genital Neoplasms, Female
- Adnexal Diseases
- Digestive System Neoplasms
- Fallopian Tube Diseases
- Abdominal Neoplasms
- Fallopian Tube Neoplasms
- Peritoneal Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Paclitaxel
- Trebananib
Other Study ID Numbers
- 20060342
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Ovarian Cancer
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Roswell Park Cancer InstituteCompletedFallopian Tube Carcinoma | Primary Peritoneal Carcinoma | Stage IIA Ovarian Cancer | Stage IIB Ovarian Cancer | Stage IIC Ovarian Cancer | Stage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian Cancer | Stage IA Ovarian Cancer | Stage IB Ovarian Cancer | Stage IC... and other conditionsUnited States
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City of Hope Medical CenterNational Cancer Institute (NCI)CompletedCancer Survivor | Stage IIIA Ovarian Epithelial Cancer | Stage IIIB Ovarian Epithelial Cancer | Stage IIIC Ovarian Epithelial Cancer | Stage IIA Ovarian Epithelial Cancer | Stage IIB Ovarian Epithelial Cancer | Stage IIC Ovarian Epithelial Cancer | Stage IA Ovarian Epithelial Cancer | Stage IB Ovarian... and other conditionsUnited States
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Massachusetts General HospitalJohns Hopkins University; M.D. Anderson Cancer Center; National Cancer Institute... and other collaboratorsRecruitingOvarian Neoplasms | Fallopian Tube Neoplasms | Stage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage... and other conditionsUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedOvarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Stage IV Ovarian Germ Cell Tumor | Ovarian Sarcoma | Malignant Ovarian Epithelial Tumor | Ovarian Carcinosarcoma | Ovarian Brenner Tumor | Ovarian Mucinous... and other conditionsUnited States
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Eve RodlerNot yet recruitingBreast Cancer | Ovarian Cancer | Breast Neoplasm | Breast Carcinoma | Breast Cancer Stage IV | Breast Cancer Stage I | Breast Cancer Stage II | Invasive Breast Cancer | Cancer, Breast | Breast Cancer Stage III | Ovary Cancer | Malignant Tumor of Breast | Ovarian Cancer Stage IIIC | Ovarian Cancer Stage IV | Ovarian Cancer... and other conditionsUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedStage IIA Fallopian Tube Cancer | Stage IIA Ovarian Cancer | Stage IIB Fallopian Tube Cancer | Stage IIB Ovarian Cancer | Stage IIC Fallopian Tube Cancer | Stage IIC Ovarian Cancer | Stage IIIA Fallopian Tube Cancer | Stage IIIA Ovarian Cancer | Stage IIIA Primary Peritoneal Cancer | Stage IIIB Fallopian... and other conditionsUnited States
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University of WashingtonNational Cancer Institute (NCI)CompletedCaregiver | Stage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
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University of WashingtonMinnesota Ovarian Cancer AllianceTerminatedStage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage IVA Ovarian Cancer AJCC v8 | Stage IVB Ovarian... and other conditionsUnited States
Clinical Trials on AMG 386
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AmgenCompletedCarcinoma | Cancer | Ovarian Cancer | Fallopian Tube Cancer | Solid Tumors | Oncology | Tumors | Metastases | Gynecological MalignanciesBelgium, United States, Australia
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AmgenCompletedCarcinoma | Cancer | Metastatic Colorectal Cancer | Colorectal Cancer | Rectal Cancer | Metastatic Cancer | Colon Cancer | Gastrointestinal Cancer | Oncology | Metastases
-
National Cancer Institute (NCI)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Adult AngiosarcomaUnited States
-
AmgenCompletedAdvanced Renal Cell Carcinoma
-
AmgenCompletedCancer | Breast Cancer | Breast Neoplasms | Metastatic Cancer | Breast Tumors | Solid Tumors | Oncology | Tumors | Metastases | Locally Recurrent and Metastatic Breast CancerUnited States, Belgium, France
-
AmgenCompletedRenal Impairment | Advanced Solid Tumors | Kidney DiseaseUnited States
-
AmgenTerminatedOvarian Cancer | Fallopian Tube Cancer | Peritoneal CancerUnited States, Austria, Belgium, Italy, Netherlands, Spain, Canada, Denmark, Germany, Korea, Republic of, Russian Federation, Hong Kong, Greece, Japan
-
AmgenCompletedLocally Recurrent and Metastatic Breast CancerUnited States, United Kingdom, Denmark, Poland, Belgium, Hungary, Spain, Austria, France, Australia, Netherlands, Finland, India
-
Chong Kun Dang PharmaceuticalUnknown