Clinical trial NCT00635193: Efficacy and Safety Study of M200(Volociximab in Combination With Liposomal Doxorubicin)
Official title: A Phase 1/2, Open-Label, Adaptive, Randomized Study of Liposomal Doxorubicin With or Without M200 (Volociximab) for the Treatment of Subjects With Advanced Epithelial Ovarian Cancer or Primary Peritoneal Cancer That Have Relapsed After Prior Therapy With a Platinum/Taxane-Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer, Primary Peritoneal Cancer
Keywords: Ovarian neoplasms
Angiogenesis inhibitors
Angiogenesis
Volociximab
Ovarian cancer
Antibody
Monoclonals
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Biogen
First posted: 2008-03-13
Enrollment: 138
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label study of liposomal doxorubicin with or without volociximab for the treatment of subjects with advanced epithelial ovarian cancer or primary peritoneal cancer relapsed after prior therapy with Plat/Taxane-based chemo. Volociximab is an anti-angiogenic integrin inhibitor being developed for the treatment of solid tumors. Preclinical data with a surrogate volociximab antibody administered as monotherapy indicate encouraging efficacy in terms of tumor reduction and anti-angiogenic effects in mouse ovarian cancer xenograft models. In clinical studies, volociximab has been evaluated in several solid tumor types, including pancreatic, renal, and melanoma, with many subjects who entered the studies with progressive disease remaining progression-free for several months. In all studies in solid tumors, volociximab has shown a favorable safety profile when administered at 10 mg/kg q2wks and more recently at 15 mg/kg qwk. A study of volociximab in combination with liposomal doxorubicin in subjects with ovarian cancer or primary peritoneal cancer who have relapsed after prior platin/taxane therapies is warranted to further evaluate the drug's efficacy and safety. The investigators have thus far activated stage 2 of this study at 11/25 sites. Worldwide, the study aims to enroll 150 subjects.

Detailed description: This is an open-label study of liposomal doxorubicin with or without volociximab for the treatment of subjects with advanced epithelial ovarian cancer or primary peritoneal cancer relapsed after prior therapy with Plat/Taxane-based chemo. Volociximab is an anti-angiogenic integrin inhibitor being developed for the treatment of solid tumors. Preclinical data with a surrogate volociximab antibody administered as monotherapy indicate encouraging efficacy in terms of tumor reduction and anti-angiogenic effects in mouse ovarian cancer xenograft models. In clinical studies, volociximab has been evaluated in several solid tumor types, including pancreatic, renal, and melanoma, with many subjects who entered the studies with progressive disease remaining progression-free for several months.

Eligibility criteria: Inclusion Criteria:

* 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).
* Recurrent or persistent disease.
* Received no more than 2 prior cancer treatment regimens, at least one of which must have included a platinum/taxane based therapy. If the same regimen is given more than once, it will count as one regimen. If components of a regimen are given more than once using the same schedule, it will count as one regimen.
* At least 1 target lesion to assess response by RECIST criteria. (Tumors within a previously irradiated field are designated as non-target)
* Other protocol-defined inclusion criteria apply.

Exclusion Criteria:

* Subjects taking immunomodulatory agents including, but not limited to, interferons, interleukins, systemic steroids, cyclosporine, tacrolimus, calcineurin inhibitors, chronic low dose methotrexate, or azathioprine. (Use of inhaled or intranasal steroids or oral steroids 10 mg/day prednisone or its equivalent are permitted.)
* 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
* Evidence of bleeding diathesis or coagulopathy. (Prior history of DVT will not exclude subjects from participating in this study.)
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1.
* Non-healing wound, ulcer, or bone fracture.
* Evidence of autoimmune disease including, but not limited to, ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and other disease in which immune function or immune competence is known to be impaired.
* Active infection requiring systemic antibiotics, antivirals, or antifungals including HIV/AIDS, hepatitis B, or hepatitis C infection.
* Other protocol-defined exclusion criteria apply

Primary outcomes:
measure: To evaluate the efficacy of volociximab in combination with liposomal doxorubicin in advanced epithelial ovarian cancer or primary peritoneal cancer. To evaluate the safety and tolerability of volociximab in combination with liposomal doxorubicin.
timeFrame: 50-57 days
Secondary outcomes:
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Site Reference ID/Investigator# 75281
state: California
city: Redondo Beach
country: United States
facility: Site Reference ID/Investigator# 75275
state: California
city: Sunrise
country: United States
facility: Site Reference ID/Investigator# 75296
state: Florida
city: Atlanta
country: United States
facility: Site Reference ID/Investigator# 75299
state: Georgia
city: Savannah
country: United States
facility: Site Reference ID/Investigator# 75300
state: Georgia
city: Hinsdale
country: United States
facility: Site Reference ID/Investigator# 75301
state: Illinois
city: Baltimore
country: United States
facility: Site Reference ID/Investigator# 75274
state: Maryland
city: Jackson City
country: United States
facility: Site Reference ID/Investigator# 75294
state: Missouri
city: Oklahoma City
country: United States
facility: Site Reference ID/Investigator# 75279
state: Oklahoma
city: Corpus Christi
country: United States
facility: Site Reference ID/Investigator# 75295
state: Texas
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 75280
state: Texas
city: Danville
country: United States
facility: Site Reference ID/Investigator# 75297
state: Virginia
city: Williamsburg
country: United States
facility: Site Reference ID/Investigator# 75298
state: Virginia
city: Green Bay
country: United States
facility: Site Reference ID/Investigator# 75278
state: Wisconsin
city: Toorak Gardens
country: Australia
facility: Site Reference ID/Investigator# 75334
city: Woodville South
country: Australia
facility: Site Reference ID/Investigator# 75335
city: Antwerp
country: Belgium
facility: Site Reference ID/Investigator# 75337
city: Brussels
country: Belgium
facility: Site Reference ID/Investigator# 75336
city: Leuven
country: Belgium
facility: Site Reference ID/Investigator# 75338
city: Milan
country: Italy
facility: Site Reference ID/Investigator# 75415
city: Milan
country: Italy
facility: Site Reference ID/Investigator# 75333
city: Bialystok
country: Poland
facility: Site Reference ID/Investigator# 75344
city: Krakow
country: Poland
facility: Site Reference ID/Investigator# 75339
city: Lublin
country: Poland
facility: Site Reference ID/Investigator# 75341
city: Poznan
country: Poland
facility: Site Reference ID/Investigator# 75342
city: Poznan
country: Poland
facility: Site Reference ID/Investigator# 75343
city: Szczecin
country: Poland
facility: Site Reference ID/Investigator# 75345
city: Wroclaw
country: Poland
facility: Site Reference ID/Investigator# 75340
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 75346
city: Moscow
country: Russian Federation
facility: Site Reference ID/Investigator# 75348
city: St. Petersburg
country: Russian Federation
facility: Site Reference ID/Investigator# 75347
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 75349
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 75351
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 75352
city: Girona
country: Spain
facility: Site Reference ID/Investigator# 75350
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 75353
city: Stockholm
country: Sweden
facility: Site Reference ID/Investigator# 75354
city: Umea
country: Sweden
facility: Site Reference ID/Investigator# 75355
city: Bellinzona
country: Switzerland
facility: Site Reference ID/Investigator# 75416
Study officials:
affiliation: AbbVie
name: Mihail Obrocea, MD
role: STUDY_DIRECTOR
References: