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Phase I Study of ABT-888, PARP Inhibitor, and Pegylated Liposomal Doxorubicin (PLD) in Recurrent Gynecologic Cancer and Breast Cancer

Phase 1
18 Years
Not Enrolling
Estrogen Receptor-negative Breast Cancer, HER2-negative Breast Cancer, Male Breast Cancer, Progesterone Receptor-negative Breast Cancer, Recurrent Breast Cancer, Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer, Stage IV Breast Cancer, Triple-negative Breast Cancer

Thank you

Trial Information

Phase I Study of ABT-888, PARP Inhibitor, and Pegylated Liposomal Doxorubicin (PLD) in Recurrent Gynecologic Cancer and Breast Cancer


I. To determine the recommended Phase II dose of ABT-888 given in combination with pegylated
liposomal doxorubicin (PLD - 40 mg/m2 every 4 weeks) in patients with ovarian or breast


I. To determine the toxicity profile of the ABT-888 plus PLD combination. II. To determine
the effects of ABT-888 on the pharmacokinetics of PLD. III. To determine the efficacy of
ABT-888 plus PLD in ovarian and breast cancer.

OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified
according to prior pegylated liposomal doxorubicin hydrochloride (yes vs no).

Patients receive oral veliparib twice daily on days 1-14 and pegylated liposomal doxorubicin
hydrochloride IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.

Blood samples are collected during courses 1-3 for pharmacokinetic studies.

After completion of study therapy, patients are followed up every 3 months for 1 year and
then every 6 months for 2 years.

Inclusion Criteria:

- Histologically confirmed diagnosis of recurrent or residual epithelial ovarian
cancer, primary peritoneal carcinoma or Fallopian tube carcinoma, OR histologically
confirmed metastatic breast cancer, that is ER-negative, PR-negative, and HER2/neu
negative (as determined by local pathology laboratory)

- Histological confirmation may be from original pathology. Patient does not
require new biopsy for recurrent, residual or metastatic disease that is
clinically diagnosed

- Prior chemotherapy:

- Ovarian cancer: (a) Patients with no prior PLD exposure are eligible after
failure of platinum-containing chemotherapy; no more than 2 prior platinum
containing regimens is permitted; (b) Patients already on PLD are also eligible
if they are receiving PLD beyond 3 cycles without prohibitive (i.e. no grade 3
or 4) skin or mucosal toxicities, and showing no progressive disease compared to
a CT scan obtained 2 or more months earlier; these patients are eligible in
spite of any progression from baseline determined prematurely (i.e., applicable
to those patients who are deemed in their best interest to continue to receive
PLD after a CT obtained at 2 or 3 months has shown progression from baseline)

- Breast cancer: Patients may have received 0-2 prior chemotherapy regimens
for metastatic disease; breast cancer patients may not have received prior
PLD, and will not be eligible for the expanded cohort A

- Interval between prior chemotherapy and registration for breast and ovarian
cancer; there should be at least a 3 week interval between the last
chemotherapy regimen and registration, and the patient should have
recovered from acute toxicity related to prior therapy (6 weeks if the last
regiment included BCNU or mitomycin C)

- Patients will be categorized in the following strata based upon prior PLD
exposure: (A) Stratum A-Patients with ovarian cancer who have had prior PLD
exposure and received at least 3 cycles of PLD without prohibitive (i.e. no
grade 3 or 4 skin toxicity) and have not had progressive disease; (B)
Stratum B: Patients with ovarian or breast cancer who have had no prior PLD

- ECOG performance score 0-2

- All potential subjects should be evaluated for whether BRCA1-2 testing is medically
appropriate; individuals who have a 10% or higher risk of having a BRCA1-2 mutation
(Myriad tables at are encouraged (but not required) to have mutation
testing and results known; information regarding mutation status (positive [including
specific mutation], negative, or unknown) and projected risk of having a mutation (as
determined by Myriad tables) will be collected at the time of diagnosis

- Non-measurable and/or measurable disease by RECIST criteria, or abnormal CA-125 to
levels (in patients with ovarian cancer) at least 1.5x normal documented by two
independent measurements at least 4 weeks apart

- Ability to give voluntary informed consent and to comply with treatment and required

- Ability to tolerate oral medications

- Female subjects age >= 18 years (males with breast cancer are eligible)

- Absolute neutrophil count >= 1500/mL

- Platelets >= 100,000/mL

- Creatinine =< 1.5mg/dL

- Total bilirubin =< 1.5x institutional upper limit of normal

- AST and ALT =< 3x institutional upper limit of normal (=< 5x institutional upper
limit of normal if evidence of liver metastasis)

- Left ventricular ejection fraction at or above institutional lower limit of normal
(obtained within 8 weeks of registration by MUGA scan or echocardiogram; the same
test performed at baseline should be repeated after every 3 cycles of therapy)

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation; should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately

Exclusion Criteria:

- Known CNS metastases with active symptoms, or requiring anticonvulsive medications,
or steroids

- Prior chemotherapy (except PLD) or any investigational agent within 3 weeks prior to

- Prior radiation therapy to whole pelvis or greater amount of marrow-forming bone

- Prior or current non-gynecologic or non-breast malignancy within 5 years except
non-melanoma skin cancer

- Patients with active severe infection; known infection with HIV, Hepatitis B virus,
Hepatitis C virus, or severe concurrent illness

- Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary,
central nervous system disease) which is either poorly controlled with currently
available treatment, or which is of such severity that the investigators deem it
unwise to enter the patient on protocol

- Patients with history of seizure disorder requiring antiepileptics who have had a
seizure episode within the last 6 months

- Pregnant (positive pregnancy test) or lactating; unwillingness to use effective means
of contraception in subjects with child-bearing potential

- Evidence of complete or partial bowel obstruction or other unable to take oral

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended Phase II dose, based on incidence of DLT graded according to the NCI CTCAE version 4.0

Outcome Time Frame:

Up to 28 days

Safety Issue:


Principal Investigator

Bhavana Pothuri

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

June 2010

Completion Date:

Related Keywords:

  • Estrogen Receptor-negative Breast Cancer
  • HER2-negative Breast Cancer
  • Male Breast Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Recurrent Breast Cancer
  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • Stage IV Breast Cancer
  • Triple-negative Breast Cancer
  • Breast Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Breast Neoplasms, Male
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms



Weill Medical College of Cornell University New York, New York  10021
Montefiore Medical Center Bronx, New York  10467-2490
New York University Langone Medical Center New York, New York  10016
Columbia University Medical Center New York, New York  10032
Montefiore Medical Center-Weiler Division Bronx, New York  10461