Phase 2 AMG 386 in Combination With Paclitaxel for Subjects With Advanced Recurrent Epithelial Ovarian or Primary Peritoneal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00479817
First received: May 24, 2007
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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

Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Drug: AMG 386
Drug: Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and Tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Objective Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Modified RECIST/CA-125 Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • CA-125 Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Estimate of reduction in tumor burden [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence of AEs and significant laboratory changes [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to Progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change from baseline in blood levels of CA-125 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time-adjusted area under the curve for PROs [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • AMG 386 Pharmacokinetic parameters [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence of the occurence of AMG 386 Antibody formation [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 161
Study Start Date: July 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Paclitaxel 80 mg/m2 IV QW (3 on/1 off) + AMG 386 10 mg/kg IV QW
Drug: AMG 386
10mg/kg (Arm A) or 3mg/kg (Arm B) delivered IV weekly.
Drug: Paclitaxel
Chemotherapy. 80mg/m2 delivered 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
Drug: AMG 386
10mg/kg (Arm A) or 3mg/kg (Arm B) delivered IV weekly.
Drug: Paclitaxel
Chemotherapy. 80mg/m2 delivered IV QW (3 on / 1 off).
Active Comparator: Arm C
Paclitaxel 80 mg/m2 IV QW (3 on/! off) + AMG 386 placebo
Drug: Paclitaxel
Chemotherapy. 80mg/m2 delivered IV QW (3 on / 1 off).

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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

Exclusion 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00479817

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00479817     History of Changes
Other Study ID Numbers: 20060342
Study First Received: May 24, 2007
Last Updated: July 16, 2014
Health Authority: Australia: Therapeutic Goods Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
India: Central Drugs Standard Control Organization
United States: Food and Drug Administration
United States: Western Institutional Review Board

Keywords provided by Amgen:
Advanced Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014