Know Cancer

or
forgot password

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


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Ovarian Cancer

Thank you

Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Objective response rate between the two treatment arms (ABT-888 + temozolomide versus the PLD) will be based on tumor measurements and CA-125 levels.

Outcome Time Frame:

Screening to survival follow-up (every 3 months for 3 years)

Safety Issue:

Yes

Principal Investigator

Mark D McKee, MD

Investigator Role:

Study Director

Investigator Affiliation:

AbbVie

Authority:

United States: Food and Drug Administration

Study ID:

M10-757

NCT ID:

NCT01113957

Start Date:

March 2010

Completion Date:

September 2013

Related Keywords:

  • Ovarian Cancer
  • Ovarian Cancer
  • Ovarian Neoplasms

Name

Location

Site Reference ID/Investigator# 25028Duarte, California  91010
Site Reference ID/Investigator# 25024Encino, California  91436
Site Reference ID/Investigator# 25034Los Angeles, California  90048
Site Reference ID/Investigator# 25037Newport Beach, California  92663
Site Reference ID/Investigator# 25030Chicago, Illinois  60637
Site Reference ID/Investigator# 27837Park Ridge, Illinois  60068
Site Reference ID/Investigator# 25039Peoria, Illinois  61615-7828
Site Reference ID/Investigator# 25038Albuquerque, New Mexico  87131
Site Reference ID/Investigator# 25023New York, New York  10065
Site Reference ID/Investigator# 25041Chapel Hill, North Carolina  27599-7570
Site Reference ID/Investigator# 25029Hilliard, Ohio  43026
Site Reference ID/Investigator# 25543Oklahoma City, Oklahoma  73104
Site Reference ID/Investigator# 25036Philadelphia, Pennsylvania  19111
Site Reference ID/Investigator# 25042Pittsburgh, Pennsylvania  15213
Site Reference ID/Investigator# 25027Houston, Texas  77030-4009