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

NCT ID: NCT00635193

Last Updated: 2013-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2009-10-31

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.

Conditions

Ovarian Cancer, Primary Peritoneal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Three subjects will be treated with liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab, 7.5 mg/kg qwk

Group Type: OTHER

M200 (Volociximab)

Intervention Type: DRUG

7.5 mg/kg, IV infusion every week until disease progression

Liposomal Doxorubicin

Intervention Type: DRUG

40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.

Cohort 2

liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab 15 mg/kg qwk

Group Type: OTHER

Liposomal Doxorubicin

Intervention Type: DRUG

40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.

M200 (Volociximab)

Intervention Type: DRUG

15 mg/kg, IV infusions every week until disease progression

Group A

liposomal doxorubicin, 40 mg/m2 q4wk

Group Type: OTHER

Liposomal Doxorubicin

Intervention Type: DRUG

40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.

Group B

liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab 15 mg/kg q2wk (or other dose and schedule)

Group Type: OTHER

Liposomal Doxorubicin

Intervention Type: DRUG

40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.

M200 (Volociximab)

Intervention Type: DRUG

15 mg/kg, IV infustions every other week until disease progression

Group C

liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab 15 mg/kg qwk (or other dose and schedule)

Group Type: OTHER

Liposomal Doxorubicin

Intervention Type: DRUG

40 mg/m2, IV infustions every 4 weeks until disease progression, the maxium number of doses a subject can receive is 12.

M200 (Volociximab)

Intervention Type: DRUG

15 mg/kg, IV infusions every week until disease progression

Interventions

M200 (Volociximab)

7.5 mg/kg, IV infusion every week until disease progression

Intervention Type: 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.

Intervention Type: DRUG

M200 (Volociximab)

15 mg/kg, IV infusions every week until disease progression

Intervention Type: DRUG

M200 (Volociximab)

15 mg/kg, IV infustions every other week until disease progression

Intervention Type: DRUG

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)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: collaborator

AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mihail Obrocea, MD

Role: STUDY_DIRECTOR

AbbVie

Locations

Site Reference ID/Investigator# 75281

Anaheim, California, United States

Site Reference ID/Investigator# 75275

Redondo Beach, California, United States

Site Reference ID/Investigator# 75296

Sunrise, Florida, United States

Site Reference ID/Investigator# 75299

Atlanta, Georgia, United States

Site Reference ID/Investigator# 75300

Savannah, Georgia, United States

Site Reference ID/Investigator# 75301

Hinsdale, Illinois, United States

Site Reference ID/Investigator# 75274

Baltimore, Maryland, United States

Site Reference ID/Investigator# 75294

Jackson, Missouri, United States

Site Reference ID/Investigator# 75279

Oklahoma City, Oklahoma, United States

Site Reference ID/Investigator# 75295

Corpus Christi, Texas, United States

Site Reference ID/Investigator# 75280

Dallas, Texas, United States

Site Reference ID/Investigator# 75297

Danville, Virginia, United States

Site Reference ID/Investigator# 75298

Williamsburg, Virginia, United States

Site Reference ID/Investigator# 75278

Green Bay, Wisconsin, United States

Site Reference ID/Investigator# 75334

Toorak Gardens, , Australia

Site Reference ID/Investigator# 75335

Woodville South, , Australia

Site Reference ID/Investigator# 75337

Antwerp, , Belgium

Site Reference ID/Investigator# 75336

Brussels, , Belgium

Site Reference ID/Investigator# 75338

Leuven, , Belgium

Site Reference ID/Investigator# 75415

Milan, , Italy

Site Reference ID/Investigator# 75333

Milan, , Italy

Site Reference ID/Investigator# 75344

Bialystok, , Poland

Site Reference ID/Investigator# 75339

Krakow, , Poland

Site Reference ID/Investigator# 75341

Lublin, , Poland

Site Reference ID/Investigator# 75342

Poznan, , Poland

Site Reference ID/Investigator# 75343

Poznan, , Poland

Site Reference ID/Investigator# 75345

Szczecin, , Poland

Site Reference ID/Investigator# 75340

Wroclaw, , Poland

Site Reference ID/Investigator# 75346

Moscow, , Russia

Site Reference ID/Investigator# 75348

Moscow, , Russia

Site Reference ID/Investigator# 75347

Saint Petersburg, , Russia

Site Reference ID/Investigator# 75349

Barcelona, , Spain

Site Reference ID/Investigator# 75351

Barcelona, , Spain

Site Reference ID/Investigator# 75352

Barcelona, , Spain

Site Reference ID/Investigator# 75350

Girona, , Spain

Site Reference ID/Investigator# 75353

Madrid, , Spain

Site Reference ID/Investigator# 75354

Stockholm, , Sweden

Site Reference ID/Investigator# 75355

Umeå, , Sweden

Site Reference ID/Investigator# 75416

Bellinzona, , Switzerland

Countries

United States; Australia; Belgium; Italy; Poland; Russia; Spain; Sweden; Switzerland

References

Newhouse R, Nelissen E, El-Shakankery KH, Rogozinska E, Bain E, Veiga S, Morrison J. Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Jul 5;7(7):CD006910. doi: 10.1002/14651858.CD006910.pub3.

Reference Type: DERIVED

PMID: 37407274 (View on PubMed)

Other Identifiers

2007-000509-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

206OC202

Identifier Type: -

Identifier Source: org_study_id