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A Phase I Trial of Pegylated Liposomal Doxorubicin (PLD), Carboplatin and NCI Supplied Veliparib (ABT-888) in Recurrent Platinum Sensitive Ovarian, Primary Peritoneal and Fallopian Tube Cancer

Phase 1
18 Years
Open (Enrolling)
Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mixed Epithelial Carcinoma, Ovarian Serous Cystadenocarcinoma, Ovarian Undifferentiated Adenocarcinoma, Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer

Thank you

Trial Information

A Phase I Trial of Pegylated Liposomal Doxorubicin (PLD), Carboplatin and NCI Supplied Veliparib (ABT-888) in Recurrent Platinum Sensitive Ovarian, Primary Peritoneal and Fallopian Tube Cancer


I. To determine the maximum-tolerated doses (MTD) and dose-limiting toxicities of two
different regimens of ABT-888(veliparib) when administered with carboplatin and PLD (Doxil,
Lipodox) (doxorubicin hydrochloride) in recurrent, platinum-sensitive epithelial ovarian,
fallopian tube, or primary peritoneal cancer.

II. To assess the toxicity of these regimens using the Cancer Therapy Evaluation Program
(CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE) Version 4.0.

III. To examine the tolerability of these treatment regimens in combination with bevacizumab
at the MTD.


I. To estimate the objective response rate (complete and partial) in patients with
measurable disease.


I. To examine the relationships between platinum-free interval, activity of ABT-888
(objective response rate) and measures of breast cancer susceptibility gene 1/2 (BRCA1/2)
status including mutations, alterations, rearrangements, promoter methylation, and
immunohistochemical expression).

OUTLINE: This is a dose-escalation study of veliparib. Patients are randomized to 1 of 2
treatment arms.

ARM I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, and doxorubicin
hydrochloride intravenously (IV) over 30 minutes and carboplatin IV over 30 minutes on day
1. Some patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15.

ARM II: Patients receive veliparib PO BID on days 1-28, and doxorubicin hydrochloride and
carboplatin as in arm I. Some patients also receive bevacizumab IV over 30-90 minutes on
days 1 and 15.

In both arms, treatment repeats every 28 days for up to 10 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria:

- Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or
primary peritoneal carcinoma which is now recurrent

- Histologic documentation of the original primary tumor is required via the
pathology report

- Patients with the following histologic epithelial cell types are eligible: high-grade
serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear
cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise
specified (N.O.S.)

- Patients must have recurrence documented by elevated cancer antigen (CA)-125
(biochemical recurrence) or clinically evident measurable or non-measurable recurrent

- Patients with measurable disease must have had at least one "target lesion" to
be used to assess response on this protocol as defined by Response Evaluation
Criteria in Solid Tumors (RECIST) 1.1

- Tumors within a previously irradiated field will be designated as
"non-target" lesions unless progression is documented or a biopsy is
obtained to confirm persistence at least 90 days following completion of
radiation therapy

- Absolute neutrophil count (ANC) >= 1,500/mcL

- This ANC cannot have been induced or supported by granulocyte colony-stimulating

- Platelets >= to 100,000/mcL

- Creatinine =< 1.5 times institutional upper limit of normal (ULN)

- Bilirubin < 1.2 times ULN

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) ≤ 3.0
times ULN

- Alkaline phosphatase =< 2.5 times ULN

- LVEF greater than or equal to institutional lower limit of normal (LLN) as determined
by gated cardiac radionucleotide scan (MUGA) or echocardiogram

- Neuropathy (sensory and motor) ≤ to grade 1

- Patients must have a platinum-free interval following initial platinum-based
chemotherapy of at least 6 months at first recurrence

- Front-line therapy may have included a biologic/targeted agent (e.g.,

- Front-line treatment may have included maintenance therapy; patients receiving
maintenance therapy (biological therapy, hormonal, or taxane therapy) are
ELIGIBLE provided their platinum-free interval is at least 6 months from initial
chemotherapy AND a minimum of 4 weeks has elapsed since their last dose of
biologic/targeted or taxane therapy or a minimum of 1 week has elapsed since
their last dose of hormonal therapy

- Patients must have a Gynecologic Oncology Group (GOG) performance status of 0 or 1

- Patients of childbearing potential must have a negative pregnancy test prior to the
study entry and be practicing an effective form of contraception; if applicable,
patients must discontinue breastfeeding prior to study entry

- Patients who have met the pre-entry requirements

- Patients must have signed an Institutional Review Board (IRB)-approved informed
consent and authorization permitting release of personal health information


- Prothrombin time (PT) such that international normalized ratio (INR) is ≤ 1.5 X ULN
(or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
therapeutic warfarin) and a partial thromboplastin time (PTT) < 1.5 X ULN

- Urine protein should be screened by urine analysis; if protein is 2+ or higher,
24-hour urine protein should be obtained and the level should be < 1000 mg for
patient enrollment

- Patients treating with enoxaparin are eligible for inclusion in the study

- Bevacizumab is detrimental to fetal growth; for this reason and because anti-vascular
endothelial growth factor (VEGF) inhibitors as well as other therapeutic agents used
in this trial are known to be teratogenic, fertile women must agree to use adequate
contraceptive measures during study therapy and for at least 6 months after the
completion of bevacizumab therapy; should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, the patient should
inform the treating physician immediately

Exclusion Criteria:

- Patients who have received more than one previous regimen of chemotherapy
(maintenance is not considered a second regimen)

- No patients who have received prior veliparib (ABT-888) or any other poly-ADP-ribose
polymerase (PARP) inhibitor

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to veliparib (ABT-888) or other agents used in this study

- Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer and other specific malignancies are excluded if there is any evidence of other
malignancy being present within the last three years; patients are also excluded if
their previous cancer treatment contraindicates this protocol therapy

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis are excluded. Prior radiation for localized cancer of the breast, head and
neck, or skin is permitted, provided that it was completed more than three years
prior to registration, and the patient remains free of recurrent or metastatic

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor
(other than ovarian, fallopian tube and primary peritoneal) are excluded; patients
may have received prior adjuvant chemotherapy for localized breast cancer, provided
that it was completed more than three years prior to registration, and that the
patient remains free of recurrent or metastatic disease

- No patients with synchronous primary endometrial cancer or a history of endometrial
cancer, unless all of the following conditions are met:

- Stage not greater than IB

- No more than superficial myometrial invasion

- No vascular or lymphatic invasion

- No poorly differentiated subtypes, including papillary serous, clear cell, or
other FIGO Grade 3 lesions

- Patients with known chronic or active hepatitis or ongoing or active infection that
requires parenteral antibiotics

- Patients with concurrent severe medical problems unrelated to the malignancy that
would significantly limit full compliance with the study or expose the patient to
extreme risk or decreased life expectancy

- Patients of childbearing potential, not practicing adequate contraception, patients
who are pregnant or patients who are breastfeeding are not eligible for this trial

- Patients with seizures or a history of seizures are ineligible

- Patients with history or evidence upon physical examination of central nervous system
(CNS) disease, including primary brain tumor, any CNS metastases, or history of
cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or
subarachnoid hemorrhage within six months of the first date of treatment on this
study; patients with CNS metastases must be stable for > 3 months after treatment and
off steroid treatment prior to study enrollment

- Patients with clinically significant cardiovascular disease; this includes:

- Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm

- Congestive heart failure, myocardial infarction or unstable angina within 6
months prior to registration

- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic
medications (except for atrial fibrillation that is well controlled with
anti-arrhythmic medication)

- New York Heart Association (NYHA) Class II or higher congestive heart failure

- Grade 2 or higher peripheral ischemia brief (<24 hrs) episode of ischemia
managed non-surgically and without permanent deficit

- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to Day 1

- Known CNS disease except for treated brain metastases; treated brain metastases are
defined as having no ongoing requirement for steroids and no evidence of progression
or hemorrhage after treatment for at least 3 months, as ascertained by clinical
examination and brain imaging (magnetic resonance imaging [MRI] or computed
tomography [CT]); (stable dose of anticonvulsants are allowed); treatment for brain
metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma
Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating
physician; patients with CNS metastases treated by neurosurgical resection or brain
biopsy performed within 3 months prior to Day 1 will be excluded

- Evidence of bleeding diathesis or coagulopathy

- Patients with known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies

- Patients who cannot swallow pills

- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 6 months to day 1

- Invasive procedures defined as follows:

- Major surgical procedure, open biopsy or significant traumatic injury within 28
days prior to Day 1 therapy

- Anticipation of need for major surgical procedures during the course of the

- Core biopsy within 7 days prior to D1 therapy

Type of Study:


Study Design:

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

Outcome Measure:

MTD as determined by dose-limiting toxicity (DLT), assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Lisa Landrum

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

October 2011

Completion Date:

Related Keywords:

  • Ovarian Clear Cell Cystadenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mixed Epithelial Carcinoma
  • Ovarian Serous Cystadenocarcinoma
  • Ovarian Undifferentiated Adenocarcinoma
  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Cystadenocarcinoma
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Carcinoma, Endometrioid
  • Cystadenocarcinoma, Serous
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms



Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Cleveland Clinic FoundationCleveland, Ohio  44195
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Case Western Reserve UniversityCleveland, Ohio  44106
Hillcrest Hospital Cancer CenterMayfield Heights, Ohio  44124
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Women and Infants HospitalProvidence, Rhode Island  02905
University of Colorado Cancer Center - Anschutz Cancer PavilionAurora, Colorado  80045
Gynecologic Oncology GroupPhiladelphia, Pennsylvania  19103
Georgia Regents UniversityAugusta, Georgia  30912