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A Phase I Study of Veliparib (ABT-888) in Combination With Low-dose Fractionated Whole Abdominal Radiation Therapy (LDFWAR) in Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis

Phase 1
18 Years
Open (Enrolling)
Peritoneal Carcinomatosis, Peritoneal Cavity Metastasis, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Veliparib (ABT-888) in Combination With Low-dose Fractionated Whole Abdominal Radiation Therapy (LDFWAR) in Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis


I. Determine the maximum tolerable dose of veliparib in combination with low-dose
fractionated whole abdominal radiation therapy (LDFWAR) in patients with peritoneal
carcinomatosis from advanced solid malignancies.

II. Determine the safety and toxicity of the combination of veliparib in conjunction with
LDFWAR in patients with peritoneal carcinomatosis from advanced solid malignancies.


I. Assess clinical activity of veliparib plus LDFWAR in patients with peritoneal
carcinomatosis from advanced solid malignancies as assessed by response rate by Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

II. Evaluate if microsatellite instability or baseline levels of various deoxyribonucleic
acid (DNA) repair proteins (excision repair cross-complementing 1 [ERCC1], x-ray repair
complementing defective repair in Chinese hamster cells 1 [XRCC1], breast cancer 1, early
onset (BRCA1), breast cancer 2, early onset [BRCA2], poly [ADP-ribosyl]ation [PAR])
correlate with clinical activity of this regimen.

III. Evaluate changes in quality of life for patients treated with this regimen by serial
measurements using the Quality of Life Questionnaire Core-30 (QLQC-30) standardized

OUTLINE: This is a dose escalation study of veliparib.

Patients will take veliparib orally (PO) twice daily (BID) on days 1-21. LDFWAR will be
administered in two fractions every Monday and Friday for weeks 1-3 of each course. Courses
will be 28 days long. Three courses only of LDFWAR will be administered.

After completion of study treatment, patients are followed up every 2 months.

Inclusion Criteria:

- Patients must have histologically proven solid malignancy that is metastatic or
unresectable with metastatic peritoneal carcinomatosis; as this entity may be
difficult to image, peritoneal disease can be documented through other modalities
such as operative notes, clinical notes/symptoms, etc as well as imaging

- Patients must be refractory to standard therapy or have no acceptable standard
treatment options

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1

- Life expectancy of greater than 3 months

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

- Platelets >= 100,000/mcL

- Total bilirubin =< 1.5 X upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 X ULN

- Creatinine =< 1.5 X ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients
with creatinine levels above institutional normal

- Magnesium >= lower limit of normal (LLN)

- Calcium within normal limit (WNL)

- No surgery, hormonal therapy or chemotherapy within four weeks

- No previous abdominal radiation; if the patient has received previous pelvic
radiation there should not be any overlap between the current and previous radiation

- Toxicities of prior chemotherapy recovered to grade 1 or less except for stable grade
2 peripheral neuropathy

- Negative pregnancy test if premenopausal; 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

- Archival tumor sample collection with a tumor block is required for all enrolled
patients when available; if no block can be released per institutional policy, 10 to
20 unstained slides may be substituted; slides should have a positive charge and a
thickness of 3 to 5 microns; if the only tissue sample available is a fine needle
aspirate (FNA), the patient will still be considered eligible

- Patients with central nervous system (CNS) metastases to be stable after therapy for
> 3 months and off steroid treatment prior to study enrollment

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients who are currently receiving any other investigational agents

- Brain metastases: patients with treated and stable brain metastasis for 3 months, off
steroids will be eligible

- Patients who demonstrate any clinical evidence of bleeding

- Patients who have demonstrated an inability to swallow oral medications

- Patients who have had a documented malignant bowel obstruction (unless patient had
obstruction as their presenting symptom)

- Patients who have a known hypersensitivity to the components of the study drug, its
analogs or drugs of a similar chemical or biologic composition

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with veliparib; potential risks may also apply to other agents
used in this study

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible

- Patients who have uncontrolled ascites

- Patients with active seizures or a history of seizure are not eligible

- Patients previously treated with poly (ADP-ribose) polymerase 1 (PARP) inhibitors

Type of Study:


Study Design:

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

Outcome Measure:

Maximum tolerated dose of veliparib in combination with LDFWAR defined as the highest dose at which 0 or 1 dose-limiting toxicities are observed in six patients

Outcome Description:

Reported with exact binomial proportions and 95% confidence intervals.

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Nilofer Azad

Investigator Role:

Principal Investigator

Investigator Affiliation:

Johns Hopkins University


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

Related Keywords:

  • Peritoneal Carcinomatosis
  • Peritoneal Cavity Metastasis
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasm Metastasis
  • Carcinoma



Johns Hopkins University Baltimore, Maryland  21205
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201