Clinical trial NCT00516841: A Phase 2, Single-Arm Study of Volociximab Monotherapy in Subjects With Platinum-Resistant Advanced Epithelial Ovarian Cancer or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Peritoneal Neoplasms
Keywords: epithelial ovarian cancer
peritoneal cancer
platinum-resistant ovarian cancer
Platinum-Resistant Advanced Epithelial Ovarian Cancer or Primary Peritoneal Cancer
Lead sponsor: Facet Biotech
Sponsor class: INDUSTRY
Collaborators: name: Biogen
First posted: 2007-08-16
Enrollment: 16
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 the efficacy of voloxicimab when administered at 15 mg/kg qwk in subjects with platinum-resistant, advanced epithelial ovarian cancer or primary peritoneal cancer.


Eligibility criteria: Inclusion Criteria:

* Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information \[PHI\]).
* Females aged ≥18 years old at the time of informed consent.
* Advanced (Stage III or IV), histologically-documented epithelial ovarian cancer or primary peritoneal cancer (excluding small, round-cell histologies).
* Radiologically-documented evidence of progressive disease.
* Platinum-resistant disease defined as having a best response of SD or disease progression during or within 6 months of discontinuing a platinum-based chemotherapy (carboplatinum, cisplatinum, or another organoplatinum compound).
* Progression during or following treatment with topotecan or liposomal doxorubicin.
* Three or fewer prior chemotherapy regimens (including a platinum-based therapy).
* At least 1 measurable target lesion in accordance with RECIST criteria to assess clinical response (tumors within a previously irradiated field are designated as non-target).
* ECOG Performance Status ≤1.
* Life expectancy \>12 weeks.
* Available paraffin block or unstained paraffin sections on glass slides containing representative tumor tissue from the most recent tumor biopsy/resection.
* Subjects of child-bearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 6 months after their last dose of study treatment (about 5 half lives).

Exclusion Criteria:

* Screening clinical laboratory values:

  * Absolute neutrophil count \<1500/µL
  * Platelet count \<75,000/µL
  * Hemoglobin \<8.5 g/dL (hemoglobin may be supported by transfusion, erythropoietin, or other approved hematopoietic growth factors; darbopoeitin \[Aranesp®\] is permitted)
  * Serum bilirubin \>2.0 x upper limit of normal (ULN)
  * AST and ALT \>2.5 x ULN (AST and ALT \>5 × ULN for subjects with liver metastasis)
  * Serum creatinine \>2.0 mg/dL
  * International normalized ratio (INR) \>1.5
  * Activated partial thromboplastin time (aPTT) \>1.5 × ULN
* Clinically significant peripheral vascular disease.
* Non-epithelial ovarian tumors.
* Active infection requiring systemic antibiotics, antivirals, or antifungals including HIV/AIDS, hepatitis B, or hepatitis C infection.
* History of abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to Day 1.
* Serious, non-healing wound, or bone fracture.
* Known central nervous system or brain metastases.
* History of uncontrolled psychiatric condition within 6 months prior to Day 1.
* History of other malignancies within 3 years of Day 1, except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ (DCIS) of breast, or basal or squamous cell skin cancer.
* Evidence of autoimmune disease including, but not limited to, ulcerative colitis, Crohn's disease, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) sceloderma, or another diseases in which immune function or immune competence is known to be impaired.
* Any history of lymphoproliferative disorder.
* Known human anti-murine antibody (HAMA) and/or human anti-chimeric antibody (HACA).
* Any medical condition that may be exacerbated by bleeding, including a known bleeding disorder such as a coagulation defect, thrombocytopenia, active gastric or duodenal ulcer, or history of GI bleeding.
* Significant hemoptysis within one year prior to Study Day 1.
* Any investigational, anti-cancer therapy within 6 weeks prior to Day 1.
* Any non-investigational, anti-cancer therapy within 4 weeks prior to Day 1.
* Prior treatment with anti-angiogenic agents.
* Subjects who require treatment with an anti-coagulant with the exception of low-dose Aspirin® (≤81 mg/day), warfarin (≤1 mg/day), or heparin for IV catheter patency.
* Subjects who are taking concomitant immunomodulatory agents including, but not limited to, interferons, interleukins, systemic steroids, cyclosporine, tacrolimus, calcineurin inhibitors, chronic low-dose methotrexate, or azathioprine. (The use of inhaled or intranasal steroids or oral steroids at a dose of ≤10 mg/day prednisone or its equivalent are permitted.)
* Active, unstable severe cardiovascular disease, including poorly controlled angina, congestive heart failure (CHF), arrhythmias, myocardial infarction (MI), cardiomyopathy, atrioventricular (AV) block, electrocardiogram (ECG) evidence of acute ischemia, or significant conduction abnormality.
* History of thromboembolic or cerebrovascular events, such as stroke, or transient ischemic attack (TIA). (Note: Prior history of deep vein thrombosis will not exclude subjects from participating in this study.)
* Pregnant (positive pregnancy test) or lactating.
* Inability to comply with study and follow-up procedures.
* Any condition that, in the opinion of the Investigator, makes the subject unsuitable for study participation.
* Known hypersensitivity to murine or chimeric antibodies.
* Major surgery within 4 weeks prior to Day 1.

Primary outcomes:
measure: Efficacy as measured by objective response rate (ORR). Tumor response based on RECIST criteria.
timeFrame: Baseline, and every 8 weeks on study
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA JCCC Clinical Research Unit
state: California
city: Orange
country: United States
facility: UCI Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Hospital
state: California
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Billings
country: United States
facility: Billings Clinic (MCMRC network)
state: Montana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: Oklahoma University Health Science Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology PA, Presbyterian
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Montreal
country: Canada
facility: McGill University Hospital
state: Quebec
Study officials:
affiliation: Mary Crowley Medical Research Center
name: Carolyn Matthews, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Oncology PA, Presbyterian
name: Minal Barve, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Billings Clinic (MCMRC network)
name: James Burke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sharp Hospital
name: Dana Glenn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fox Chase Cancer Center
name: Russell Schilder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Nikki Spellman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oklahoma University Health Science Center
name: Michael Gold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Richard Penson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center
name: Mark Einstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Florida Hospital Cancer Institute
name: Robert Holloway, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Kimmel Cancer Center
name: Deborah Armstrong, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Health University Medical Center
name: Snehel Bhoola, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: London Health Sciences Center
name: Eric Winquist, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Ernst Lengyel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCLA JCCC Clinical Research Unit
name: John Glaspy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCI Medical Center
name: Krish Tewari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: James Graham Brown Cancer Center
name: C. William Helm, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: John Glaspy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cross Cancer Institute
name: Michael Sawyer, MD
role: PRINCIPAL_INVESTIGATOR
References: