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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01113957
First received: February 26, 2010
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Drug: ABT-888
Drug: pegylated liposomal doxorubicin
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Objective response rate between the two treatment arms (ABT-888 + temozolomide versus the PLD) will be based on tumor measurements and CA-125 levels. [ Time Frame: Screening to survival follow-up (every 3 months for 3 years) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate progression free survival, time to progression, overall survival, 12-month survival rate, 6-month progression free survival rate, duration of response [ Time Frame: Screening to survival follow-up (every 3 months for 3 years) ] [ Designated as safety issue: No ]
  • Safety Assessments and tolerability (i.e. ECG, clinical laboratory tests, vital signs, AE assessments, physical exams, CT scans). See section 5 for detailed information. [ Time Frame: Screening to the 30 day follow-up visit ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Screening to survival follow-up (every 3 months for 3 years). ] [ Designated as safety issue: No ]

Enrollment: 168
Study Start Date: March 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
ABT-888 in combination with temozolomide
Drug: ABT-888
Arm-A subjects will be given ABT-888 on Days 1 -7 every 28 days orally
Other Name: ABT-888, veliparib
Drug: temozolomide
Arm A subjects will be given temozolomide on days 1-5 every 28 days orally with ABT-888
Other Name: temozolomide, temodar/temodal
Active Comparator: Arm B
pegylated liposomal doxorubicin alone
Drug: pegylated liposomal doxorubicin
Arm B subjects randomized to pegylated liposomal doxorubicin on Day 1, every 28 days intravenously.
Other Name: doxil/caelyx

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01113957

  Show 32 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Mark D McKee, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01113957     History of Changes
Other Study ID Numbers: M10-757, 2009-015082-31
Study First Received: February 26, 2010
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medsafe
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Poland: Ministry of Health
Israel: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Hungary: Ministry of Health, Social and Family Affairs

Keywords provided by AbbVie:
Ovarian Cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Doxorubicin
Liposomal doxorubicin
Temozolomide
Dacarbazine
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on August 27, 2014