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

NCT01113957 | Completed Phase 2

• 2 other identifiers: M10-7572009-015082-31
• Study Type: interventional
• Target: 168
• Locations: 8 countries
• Sites: 32

Brief 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.

Conditions

Ovarian Cancer

Keywords

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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)

• 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

• 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).

Study Arms (2)

Arm A

EXPERIMENTAL

ABT-888 in combination with temozolomide

Drug: ABT-888; Drug: temozolomide

Arm B

ACTIVE COMPARATOR

pegylated liposomal doxorubicin alone

Drug: pegylated liposomal doxorubicin

Interventions

ABT-888 DRUG

Arm-A subjects will be given ABT-888 on Days 1 -7 every 28 days orally

Also known as: ABT-888, veliparib

Arm A

pegylated liposomal doxorubicin DRUG

Arm B subjects randomized to pegylated liposomal doxorubicin on Day 1, every 28 days intravenously.

Also known as: doxil/caelyx

Arm B

temozolomide DRUG

Arm A subjects will be given temozolomide on days 1-5 every 28 days orally with ABT-888

Also known as: temozolomide, temodar/temodal

Arm A

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (32)

Site Reference ID/Investigator# 25028

Duarte, California, 91010, United States

Location

Site Reference ID/Investigator# 25024

Encino, California, 91436, United States

Location

Site Reference ID/Investigator# 25034

Los Angeles, California, 90048, United States

Location

Site Reference ID/Investigator# 25037

Newport Beach, California, 92663, United States

Location

Site Reference ID/Investigator# 25030

Chicago, Illinois, 60637-1470, United States

Location

Site Reference ID/Investigator# 27837

Park Ridge, Illinois, 60068, United States

Location

Site Reference ID/Investigator# 25039

Peoria, Illinois, 61615-7828, United States

Location

Site Reference ID/Investigator# 25038

Albuquerque, New Mexico, 87131, United States

Location

Site Reference ID/Investigator# 25023

New York, New York, 10065, United States

Location

Site Reference ID/Investigator# 25041

Chapel Hill, North Carolina, 27599-7570, United States

Location

Site Reference ID/Investigator# 25029

Hilliard, Ohio, 43026, United States

Location

Site Reference ID/Investigator# 25543

Oklahoma City, Oklahoma, 73104, United States

Location

Site Reference ID/Investigator# 25036

Philadelphia, Pennsylvania, 19111, United States

Location

Site Reference ID/Investigator# 25042

Pittsburgh, Pennsylvania, 15213, United States

Location

Site Reference ID/Investigator# 25027

Houston, Texas, 77030, United States

Location

Site Reference ID/Investigator# 25128

Adelaide, 5000, Australia

Location

Site Reference ID/Investigator# 25130

Bedford Park, 5042, Australia

Location

Site Reference ID/Investigator# 25131

East Melbourne, 3002, Australia

Location

Site Reference ID/Investigator# 25133

Nedlands, 6009, Australia

Location

Site Reference ID/Investigator# 25132

Randwick, 2031, Australia

Location

Site Reference ID/Investigator# 25129

Westmead, 2145, Australia

Location

Site Reference ID/Investigator# 25166

Edmonton, T6G 1Z2, Canada

Location

Site Reference ID/Investigator# 25162

Kelowna, V1Y 5L3, Canada

Location

Site Reference ID/Investigator# 25165

Laval, H7M 3L9, Canada

Location

Site Reference ID/Investigator# 25135

Budapest, H-1125, Hungary

Location

Site Reference ID/Investigator# 25138

Haifa, 31096, Israel

Location

Site Reference ID/Investigator# 25139

Tel Aviv, 64239, Israel

Location

Site Reference ID/Investigator# 25141

Tel Litwinsky, 52621, Israel

Location

Site Reference ID/Investigator# 25402

Auckland, 1023, New Zealand

Location

Site Reference ID/Investigator# 25145

Warsaw, 02-781, Poland

Location

Site Reference ID/Investigator# 25149

Northwood, HA6 2RN, United Kingdom

Location

Site Reference ID/Investigator# 25154

Oxford, OX3 7LJ, United Kingdom

Location

Related 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.

  PMID: 23459506 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

veliparib; liposomal doxorubicin; Temozolomide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mark D McKee, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2010
• First Posted: April 30, 2010
• Study Start: March 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 6, 2018

Record last verified: 2014-06

Locations

NZ (1); HU (1); CA (3); PL (1); AU (6); GB (2); US (15); IL (3)