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

Sponsor

AbbVie (prior sponsor, Abbott) (Industry)

Overall Status

Completed

CT.gov ID

NCT00635193

Collaborator

Biogen (Industry)

138

Enrollment

Locations

Arms

Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer, Primary Peritoneal Cancer	Drug: M200 (Volociximab) Drug: Liposomal Doxorubicin Drug: M200 (Volociximab) Drug: M200 (Volociximab)	Phase 1/Phase 2

Detailed Description

Study Design

Study Type:

Interventional

Actual Enrollment :

138 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Oct 1, 2008

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

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.
Other: Cohort 2 liposomal doxorubicin, 40 mg/m2 q4wk, and volociximab 15 mg/kg qwk	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
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: 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 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: 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

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 75281	Anaheim	California	United States	92801
2	Site Reference ID/Investigator# 75275	Redondo Beach	California	United States	90277
3	Site Reference ID/Investigator# 75296	Sunrise	Florida	United States	33323
4	Site Reference ID/Investigator# 75299	Atlanta	Georgia	United States	30309
5	Site Reference ID/Investigator# 75300	Savannah	Georgia	United States	31404
6	Site Reference ID/Investigator# 75301	Hinsdale	Illinois	United States	60521
7	Site Reference ID/Investigator# 75274	Baltimore	Maryland	United States	21215
8	Site Reference ID/Investigator# 75294	Jackson City	Missouri	United States	65109
9	Site Reference ID/Investigator# 75279	Oklahoma City	Oklahoma	United States	73104
10	Site Reference ID/Investigator# 75295	Corpus Christi	Texas	United States	78404
11	Site Reference ID/Investigator# 75280	Dallas	Texas	United States	75246
12	Site Reference ID/Investigator# 75297	Danville	Virginia	United States	23185
13	Site Reference ID/Investigator# 75298	Williamsburg	Virginia	United States	23185
14	Site Reference ID/Investigator# 75278	Green Bay	Wisconsin	United States	54301
15	Site Reference ID/Investigator# 75334	Toorak Gardens		Australia	5065
16	Site Reference ID/Investigator# 75335	Woodville South		Australia	5011
17	Site Reference ID/Investigator# 75337	Antwerp		Belgium	2020
18	Site Reference ID/Investigator# 75336	Brussels		Belgium	1200
19	Site Reference ID/Investigator# 75338	Leuven		Belgium	3000
20	Site Reference ID/Investigator# 75415	Milan		Italy	20133
21	Site Reference ID/Investigator# 75333	Milan		Italy	20141
22	Site Reference ID/Investigator# 75344	Bialystok		Poland	15-027
23	Site Reference ID/Investigator# 75339	Krakow		Poland	31-531
24	Site Reference ID/Investigator# 75341	Lublin		Poland	20-090
25	Site Reference ID/Investigator# 75342	Poznan		Poland	61-001
26	Site Reference ID/Investigator# 75343	Poznan		Poland	61-848
27	Site Reference ID/Investigator# 75345	Szczecin		Poland	70-111
28	Site Reference ID/Investigator# 75340	Wroclaw		Poland	50-367
29	Site Reference ID/Investigator# 75346	Moscow		Russian Federation	129128
30	Site Reference ID/Investigator# 75348	Moscow		Russian Federation	143423
31	Site Reference ID/Investigator# 75347	St. Petersburg		Russian Federation	198255
32	Site Reference ID/Investigator# 75349	Barcelona		Spain	08035
33	Site Reference ID/Investigator# 75351	Barcelona		Spain	08036
34	Site Reference ID/Investigator# 75352	Barcelona		Spain	08208
35	Site Reference ID/Investigator# 75350	Girona		Spain	17007
36	Site Reference ID/Investigator# 75353	Madrid		Spain	28040
37	Site Reference ID/Investigator# 75354	Stockholm		Sweden	17176
38	Site Reference ID/Investigator# 75355	Umea		Sweden	901 85
39	Site Reference ID/Investigator# 75416	Bellinzona		Switzerland	6500