Brief Title
Pegylated Liposomal Doxorubicin Hydrochloride, Carboplatin, Veliparib, and Bevacizumab in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
Official Title
A Phase I Trial of Pegylated Liposomal Doxorubicin (PLD), Carboplatin and NCI Supplied Veliparib (ABT-888), and NCI Supplied Bevacizumab in Recurrent Platinum Sensitive Ovarian, Primary Peritoneal and Fallopian Tube Cancer
Brief Summary
This phase I trial studies the side effects and the best dose of veliparib when given
together with pegylated liposomal doxorubicin hydrochloride, carboplatin, and bevacizumab in
treating patients with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
that has returned after previous treatment. Veliparib may stop the growth of tumor cells by
blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as
pegylated liposomal doxorubicin hydrochloride and carboplatin, may stop the growth of tumor
cells by, either by killing the cells, by stopping them from dividing, or by stopping them
from spreading. Monoclonal antibodies, such as bevacizumab, can block tumor growth by
blocking the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth
of tumors by blocking the growth of new blood vessels necessary for tumor growth. Giving
veliparib together with pegylated liposomal doxorubicin hydrochloride, carboplatin, and
bevacizumab may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES:
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) (pegylated liposomal 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.
SECONDARY OBJECTIVES:
I. To estimate the objective response rate (complete and partial) in patients with measurable
disease.
TERTIARY OBJECTIVES:
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 assigned to 1 of 2
treatment arms.
REGIMEN I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, and
pegylated liposomal doxorubicin hydrochloride intravenously (IV) over 1 hour and carboplatin
IV over 30 minutes on day 1.
REGIMEN II: Patients receive veliparib PO BID on days 1-28, and pegylated liposomal
doxorubicin hydrochloride and carboplatin as in Regimen I.
BEVACIZUMAB: Once the MTD for veliparib has been determined, 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 quarterly for 1 year.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
DLT assessed by NCI CTCAE version 4
Secondary Outcome
Objective tumor response (complete and partial response)
Condition
Ovarian Clear Cell Cystadenocarcinoma
Intervention
Bevacizumab
Study Arms / Comparison Groups
Regimen I (intermittent veliparib)
Description: Patients receive veliparib PO BID on days 1-7, and pegylated liposomal doxorubicin hydrochloride IV over 1 hour and carboplatin IV over 30 minutes on day 1.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
41
Start Date
October 11, 2011
Completion Date
February 11, 2017
Primary Completion Date
June 8, 2016
Eligibility Criteria
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
disease
- Biochemical recurrence is defined as a CA-125 greater than or equal to two times
the upper normal limit; patients whose CA-125 is less than 100 U/mL must undergo
a second confirmatory value within a period of not more than 4 weeks; patients
with a level greater than or equal to 100 U/mL may be entered without
confirmatory measurement; the CA-125 assessment for eligibility must be done at
least 4 weeks after paracentesis or other surgical procedures
- Detectable (non-measurable) disease is defined as symptomatic ascites or pleural
effusions, solid and/or cystic abnormalities on radiographic imaging that do not
meet Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 definitions for
target lesions and/or biopsy proven recurrence
- Measurable disease will be defined by RECIST 1.1; measurable disease is defined
as at least one lesion that can be accurately measured in at least one dimension
(longest diameter to be recorded); each lesion must be >= 10 mm when measured by
computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement
by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be
>= 15 mm in short axis when measured by CT or MRI
- Patients with measurable disease must have had at least one "target lesion" to be
used to assess response on this protocol as defined by 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) greater than or equal to 1,500/mcl
- This ANC cannot have been induced or supported by granulocyte colony-stimulating
factors
- Platelets greater than or equal 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 glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0
times ULN
- Alkaline phosphatase =< 2.5 times ULN
- Left ventricular ejection fraction (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) less than or equal 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., bevacizumab)
- NOTE: 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
- ADDITIONAL CRITERIA FOR PATIENTS BEING TREATED ON BEVACIZUMAB COHORT
- 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
- 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)
- Patients who have received prior ABT-888 or any other poly-adenosine diphosphate
(ADP)--ribose polymerase (PARP) inhibitor
- Patients who have received prior PLD
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 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 disease
- 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
- 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 International Federation of Gynecology and Obstetrics (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 who cannot swallow pills
- ADDITIONAL CRITERIA FOR PATIENTS BEING TREATED ON BEVACIZUMAB COHORT:
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to bevacizumab
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with bevacizumab
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible
- 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
- Serious non-healing wound, ulcer, or bone fracture
- 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 study
- Core biopsy within 7 days prior to day 1 (D1) therapy
- 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
- Patients with clinically significant cardiovascular disease are excluded
- Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 160
mm Hg and/or diastolic blood pressure [DBP] > 90 mm Hg despite antihypertensive
medication)
- History of cerebrovascular accident (CVA) within 6 months
- History of myocardial infraction or unstable angina within 6 months
- New York Heart Association grade II or greater congestive heart failure
- Serious and inadequately controlled cardiac arrhythmia
- Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
- Clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Patients with known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Lisa Landrum, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01459380
Organization ID
NCI-2011-01977
Secondary IDs
NCI-2011-01977
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Collaborators
NRG Oncology
Study Sponsor
Lisa Landrum, Principal Investigator, NRG Oncology
Verification Date
July 2019