A Trial of ABT-888 in Combination With Temozolomide Versus Pegylated Liposomal Doxorubicin Alone in Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase 2 Randomized Clinical Trial of ABT-888 in Combination With Temozolomide Versus Pegylated Liposomal Doxorubicin Alone in Subjects With Recurrent High Grade Serous Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01113957
• Other study ID #: M10-757
• Secondary ID: 2009-015082-31
• Status: Completed
• Phase: Phase 2
• Start date: March 2010
• Est. completion date: June 2013

Study information

• Verified date: June 2014
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the objective response rate of ABT-888 when given in combination with temozolomide versus pegylated liposomal doxorubicin (PLD) alone in subjects with recurrent high grade serous ovarian cancer.

Description:

Safety assessments and tolerability will be assessed through electrocardiograms (ECG). clinical laboratory tests, vital signs, Adverse Event assessments, and physical exams. Baseline radiographic tumor assessments, including CT scans of the chest, abdomen and pelvis will be obtained. Radiologic assessments and CA-125 measurements will also be performed every 8 weeks during dosing and following completion of dosing until disease progression. Study visits will be conducted weekly for the first 2 cycles and on Day 1 of each subsequent cycle, at the Final Visit and 30 day Follow-up Visit. Study visits will include physical examination, complete blood count (CBC) and chemistries. A urinalysis tests will be performed at Screening and Final Visit. An ECG will be performed at Screening, Cycle 1 Day 1 and at the Final Study Visit. A left ventricular ejection fraction (LVEF) will be measured by Echocardiogram or Multiple Gated Acquisition (MUGA) scan on all subjects at Screening. Subjects randomized to the PLD arm will have an echocardiogram or MUGA performed at the Final Study Visit and at the discretion of the Investigator throughout the study. Adverse events will be assessed at every visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Subject must have histologically (or cytologically) confirmed recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer.

• Subjects must have had at least 1 platinum containing chemotherapy regimen and no more than a total of 3 DNA damaging or cytotoxic regimens in the last 5 years. Less than a full dose of a DNA damaging agent, possibly due to reasons such as toxicity or documented allergic reaction are allowed. Previous treatments with biologics (including catumaxomab, tigatuzumab, abagovomab, and bevacizumab), vaccines, immunostimulants, hormonal agents, and signal transduction inhibitors (e.g., pazopanib, sorafenib, sunitinib, temsirolimus) are allowed and are not counted towards the limit of 3.

• Subjects who are resistant to platinum-based therapy; or sensitive to but are unable to tolerate platinum-based therapy (i.e., deemed toxic or have a documented platinum allergy). Subjects must have at least a > 3 month treatment free interval from the last dose of platinum based therapy.

• Subject must be eligible for PLD treatment.

• Subject has either:

• Measurable disease, defined as at least 1 unidimensionally measurable lesion on a computed tomography (CT) scan as defined by response evaluation criteria in solid tumors (RECIST) version 1.1 OR

• Non-measurable disease with an elevation of serum CA-125 level by Gynecologic Cancer Intergroup (GCIG) criteria (baseline sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment).

• Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.

• Subject must have adequate hematologic, renal and hepatic function as follows:

• Bone Marrow: Absolute neutrophil count (ANC = 1,500/mm3 (1.5 x 109/L); Platelets = 100,000/mm3 (100 x 109/L); Hemoglobin = 9.5 g/dL (1.4 mmol/L);

• Renal function: Serum creatinine = 1.5 x upper normal limit of institution's normal range OR creatinine clearance = 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal;

• Hepatic function: Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) = 2.5 x the upper normal limit of institution's normal range. For subjects with liver metastases, AST and/or ALT < 5 x the upper normal limit of institution's normal range; Bilirubin = 1.5 x the upper normal limit of institution's normal range;

• Partial thromboplastin time (PTT) must be = 1.5 x the upper normal limit of institution's normal range and international normalized ratio (INR) < 1.5. Subjects on anticoagulant (such as Coumadin) are allowed on study and will have PTT and INR as determined by the Investigator

• Women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and for 90 days following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test within 21 days prior to initiation of treatment and a negative urine pregnancy test on Cycle 1 Day 1. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

Exclusion Criteria:

• Subject has previously received a poly-ADP-ribose)-polymerase (PARP) inhibitor except a single dose from Cancer Therapy Evaluation Program (CTEP) Phase 0 (A06-161) study.

• Subjects who have a history of hypersensitivity reactions to a conventional formulation of doxorubicin hydrocloride (HCL) or the components of PLD.

• The subject has received an anticancer agents or an investigational agent within 28 days prior to study drug administration. Subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to previous anticancer treatment are excluded.

• Subject has undergone major surgery within the previous 28 days prior to study drug administration.

• Subjects with prior radiotherapy to any portion of the abdominal cavity and pelvis, unless for the treatment of ovarian, primary peritoneal or fallopian tube cancer. Subject must have completed radiation at least 28 days prior to study drug administration and have measurable disease outside the radiation field or documented progression of lesions within a previously radiated field.

• Subjects with a known history of brain metastases.

• Clinically significant and uncontrolled major medical condition(s) including but not limited to:

• Active uncontrolled infection

• Symptomatic congestive heart failure

• Unstable angina pectoris or cardiac arrhythmia

• Psychiatric illness/social situation that would limit compliance with study requirements

• Any medical condition, which is in the opinion of the Study Investigator, places the subject at an unacceptably high risk for toxicities

• Subject is pregnant or lactating.

• Subjects who requires parenteral nutrition, or tube feeding or has evidence of partial bowel obstruction or perforation.

• The subject has had another active malignancy within the past five years except for any cancer in situ considered cured or non-melanoma carcinoma of the skin. Questions regarding the inclusion of individual subject should be directed to the Abbott Medical Monitor.

• Subject has previously received a poly-ADP-ribose)-polymerase (PARP) inhibitor except a single dose from Cancer Therapy Evaluation Program (CTEP) Phase 0 (A06-161) study. - Subjects who have a history of hypersensitivity reactions to a conventional formulation of doxorubicin hydrocloride (HCL) or the components of PLD.

• The subject has received an anticancer agents or an investigational agent within 28 days prior to study drug administration. Subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to previous anticancer treatment are excluded.

• Subject has undergone major surgery within the previous 28 days prior to study drug administration.

• Subjects with prior radiotherapy to any portion of the abdominal cavity and pelvis, unless for the treatment of ovarian, primary peritoneal or fallopian tube cancer. Subject must have completed radiation at least 28 days prior to study drug administration and have measurable disease outside the radiation field or documented progression of lesions within a previously radiated field.

• Subjects with a known history of brain metastases.

• Clinically significant and uncontrolled major medical condition(s) including but not limited to:

• Active uncontrolled infection

• Symptomatic congestive heart failure

• Unstable angina pectoris or cardiac arrhythmia

• Psychiatric illness/social situation that would limit compliance with study requirements

• Any medical condition, which is in the opinion of the Study Investigator, places the subject at an unacceptably high risk for toxicities

• Subject is pregnant or lactating.

• Subjects who requires parenteral nutrition, or tube feeding or has evidence of partial bowel obstruction or perforation.

• The subject has had another active malignancy within the past five years except for any cancer in situ considered cured or non-melanoma carcinoma of the skin. Questions regarding the inclusion of individual subject should be directed to the Abbott Medical Monitor.

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• ABT-888
Arm-A subjects will be given ABT-888 on Days 1 -7 every 28 days orally
• pegylated liposomal doxorubicin
Arm B subjects randomized to pegylated liposomal doxorubicin on Day 1, every 28 days intravenously.
• temozolomide
Arm A subjects will be given temozolomide on days 1-5 every 28 days orally with ABT-888

Locations

Country	Name	City	State
Australia	Site Reference ID/Investigator# 25128	Adelaide
Australia	Site Reference ID/Investigator# 25130	Bedford Park
Australia	Site Reference ID/Investigator# 25131	East Melbourne
Australia	Site Reference ID/Investigator# 25133	Nedlands
Australia	Site Reference ID/Investigator# 25132	Randwick
Australia	Site Reference ID/Investigator# 25129	Westmead
Canada	Site Reference ID/Investigator# 25166	Edmonton
Canada	Site Reference ID/Investigator# 25162	Kelowna
Canada	Site Reference ID/Investigator# 25165	Laval
Hungary	Site Reference ID/Investigator# 25135	Budapest
Israel	Site Reference ID/Investigator# 25138	Haifa
Israel	Site Reference ID/Investigator# 25139	Tel Aviv
Israel	Site Reference ID/Investigator# 25141	Tel Hashomer
New Zealand	Site Reference ID/Investigator# 25402	Auckland
Poland	Site Reference ID/Investigator# 25145	Warsaw
United Kingdom	Site Reference ID/Investigator# 25149	Northwood
United Kingdom	Site Reference ID/Investigator# 25154	Oxford
United States	Site Reference ID/Investigator# 25038	Albuquerque	New Mexico
United States	Site Reference ID/Investigator# 25041	Chapel Hill	North Carolina
United States	Site Reference ID/Investigator# 25030	Chicago	Illinois
United States	Site Reference ID/Investigator# 25028	Duarte	California
United States	Site Reference ID/Investigator# 25024	Encino	California
United States	Site Reference ID/Investigator# 25029	Hilliard	Ohio
United States	Site Reference ID/Investigator# 25027	Houston	Texas
United States	Site Reference ID/Investigator# 25034	Los Angeles	California
United States	Site Reference ID/Investigator# 25023	New York	New York
United States	Site Reference ID/Investigator# 25037	Newport Beach	California
United States	Site Reference ID/Investigator# 25543	Oklahoma City	Oklahoma
United States	Site Reference ID/Investigator# 27837	Park Ridge	Illinois
United States	Site Reference ID/Investigator# 25039	Peoria	Illinois
United States	Site Reference ID/Investigator# 25036	Philadelphia	Pennsylvania
United States	Site Reference ID/Investigator# 25042	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hungary,  Israel,  New Zealand,  Poland,  United Kingdom, 

References & Publications (1)

Elit L, Hirte H. Palliative systemic therapy for women with recurrent epithelial ovarian cancer: current options. Onco Targets Ther. 2013;6:107-18. doi: 10.2147/OTT.S30238. Epub 2013 Feb 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate between the two treatment arms (ABT-888 + temozolomide versus the PLD) will be based on tumor measurements and CA-125 levels.		Screening to survival follow-up (every 3 months for 3 years)
Secondary	Evaluate progression free survival, time to progression, overall survival, 12-month survival rate, 6-month progression free survival rate, duration of response		Screening to survival follow-up (every 3 months for 3 years)
Secondary	Safety Assessments and tolerability (i.e. ECG, clinical laboratory tests, vital signs, AE assessments, physical exams, CT scans). See section 5 for detailed information.		Screening to the 30 day follow-up visit
Secondary	Evaluate Quality of Life and performance status will be done through the use of FACT-O quality of fife questionnaire, EQ5D questionnaire and ECOG performance status.		Screening to survival follow-up (every 3 months for 3 years).