Efficacy and Safety Study of M200(Volociximab in Combination With Liposomal Doxorubicin)

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer, Primary Peritoneal Cancer
• Intervention / Treatment: Drug: M200 (Volociximab); Drug: Liposomal Doxorubicin; Drug: M200 (Volociximab); Drug: M200 (Volociximab)

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.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Toorak Gardens, Australia, 5065
    • Site Reference ID/Investigator# 75334
  • Woodville South, Australia, 5011
    • Site Reference ID/Investigator# 75335
• Belgium
  • Antwerp, Belgium, 2020
    • Site Reference ID/Investigator# 75337
  • Brussels, Belgium, 1200
    • Site Reference ID/Investigator# 75336
  • Leuven, Belgium, 3000
    • Site Reference ID/Investigator# 75338
• Italy
  • Milan, Italy, 20133
    • Site Reference ID/Investigator# 75415
  • Milan, Italy, 20141
    • Site Reference ID/Investigator# 75333
• Poland
  • Bialystok, Poland, 15-027
    • Site Reference ID/Investigator# 75344
  • Krakow, Poland, 31-531
    • Site Reference ID/Investigator# 75339
  • Lublin, Poland, 20-090
    • Site Reference ID/Investigator# 75341
  • Poznan, Poland, 61-001
    • Site Reference ID/Investigator# 75342
  • Poznan, Poland, 61-848
    • Site Reference ID/Investigator# 75343
  • Szczecin, Poland, 70-111
    • Site Reference ID/Investigator# 75345
  • Wroclaw, Poland, 50-367
    • Site Reference ID/Investigator# 75340
• Russian Federation
  • Moscow, Russian Federation, 129128
    • Site Reference ID/Investigator# 75346
  • Moscow, Russian Federation, 143423
    • Site Reference ID/Investigator# 75348
  • St. Petersburg, Russian Federation, 198255
    • Site Reference ID/Investigator# 75347
• Spain
  • Barcelona, Spain, 08035
    • Site Reference ID/Investigator# 75349
  • Barcelona, Spain, 08036
    • Site Reference ID/Investigator# 75351
  • Barcelona, Spain, 08208
    • Site Reference ID/Investigator# 75352
  • Girona, Spain, 17007
    • Site Reference ID/Investigator# 75350
  • Madrid, Spain, 28040
    • Site Reference ID/Investigator# 75353
• Sweden
  • Stockholm, Sweden, 17176
    • Site Reference ID/Investigator# 75354
  • Umea, Sweden, 901 85
    • Site Reference ID/Investigator# 75355
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Site Reference ID/Investigator# 75416
• United States
  • California
    • Anaheim, California, United States, 92801
      • Site Reference ID/Investigator# 75281
    • Redondo Beach, California, United States, 90277
      • Site Reference ID/Investigator# 75275
  • Florida
    • Sunrise, Florida, United States, 33323
      • Site Reference ID/Investigator# 75296
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Site Reference ID/Investigator# 75299
    • Savannah, Georgia, United States, 31404
      • Site Reference ID/Investigator# 75300
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Site Reference ID/Investigator# 75301
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Site Reference ID/Investigator# 75274
  • Missouri
    • Jackson City, Missouri, United States, 65109
      • Site Reference ID/Investigator# 75294
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Site Reference ID/Investigator# 75279
  • Texas
    • Corpus Christi, Texas, United States, 78404
      • Site Reference ID/Investigator# 75295
    • Dallas, Texas, United States, 75246
      • Site Reference ID/Investigator# 75280
  • Virginia
    • Danville, Virginia, United States, 23185
      • Site Reference ID/Investigator# 75297
    • Williamsburg, Virginia, United States, 23185
      • Site Reference ID/Investigator# 75298
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Site Reference ID/Investigator# 75278

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1; Three subjects will be treated with liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab, 7.5 mg/kg qwk	Drug: M200 (Volociximab); 7.5 mg/kg, IV infusion every week until disease progression; Drug: Liposomal Doxorubicin; 40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.; Drug: M200 (Volociximab); 15 mg/kg, IV infusions every week until disease progression; Drug: M200 (Volociximab); 15 mg/kg, IV infustions every other week until disease progression
Other: Cohort 2; liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab 15 mg/kg qwk	Drug: M200 (Volociximab); 7.5 mg/kg, IV infusion every week until disease progression; Drug: Liposomal Doxorubicin; 40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.; Drug: M200 (Volociximab); 15 mg/kg, IV infusions every week until disease progression; Drug: M200 (Volociximab); 15 mg/kg, IV infustions every other week until disease progression
Other: Group A; liposomal doxorubicin, 40 mg/m2 q4wk	Drug: Liposomal Doxorubicin; 40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.
Other: Group B; liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab 15 mg/kg q2wk (or other dose and schedule)	Drug: M200 (Volociximab); 7.5 mg/kg, IV infusion every week until disease progression; Drug: Liposomal Doxorubicin; 40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.; Drug: M200 (Volociximab); 15 mg/kg, IV infusions every week until disease progression; Drug: M200 (Volociximab); 15 mg/kg, IV infustions every other week until disease progression
Other: Group C; liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab 15 mg/kg qwk (or other dose and schedule)	Drug: M200 (Volociximab); 7.5 mg/kg, IV infusion every week until disease progression; Drug: Liposomal Doxorubicin; 40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.; Drug: M200 (Volociximab); 15 mg/kg, IV infusions every week until disease progression; Drug: M200 (Volociximab); 15 mg/kg, IV infustions every other week until disease progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	50-57 days

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Collaborators: Biogen

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Estimate): January 18, 2013
• Last Update Submitted That Met QC Criteria: January 10, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Ovarian cancer; Antibody; Angiogenesis; Monoclonals; Ovarian neoplasms; Angiogenesis inhibitors; Volociximab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin; Antibodies, Monoclonal; Volociximab
• Other Study ID Numbers: 206OC202; 2007-000509-31 (EudraCT Number)