| Eligibility |
Inclusion Criteria:
- Patients must have histologically confirmed malignancy that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective; patients with either solid tumors or non-Hodgkin's lymphoma
are eligible
- At the recommended Phase II dose level, an additional 6 to 12 patients in each
group with the following criteria will be enrolled: documented breast cancer
(BRCA)1/BRC2 mutation, triple-negative breast cancer defined as estrogen receptor
(ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth
factor receptor (HER)2-negative, or patients who would benefit from a
cyclophosphamide-based regimen
- On the schedule of ABT-888 given for 7 or 14 days, only patients with metastatic
breast cancer will be enrolled
- Patients must be >= 4 weeks since prior chemotherapy or radiation therapy (>= 6 weeks
if the last regimen included carmustine [BCNU] or mitomycin C); patients previously
treated with cyclophosphamide should not be necessarily excluded
- Patients with non-Hodgkin's lymphoma that is amenable to hematopoietic stem cell
transplantation with curative intent may participate only if stem cell transplant is
refused or is not indicated
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 2 months
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
institutional upper limit of normal (ULN), =< 5 x ULN if known hepatic metastases
- Creatinine within normal institutional limits OR creatinine clearance >= 60
ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time
(PTT) =< 1.2 X institutional ULN
- 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
- Patients enrolled in a group where the treatment is adriamycin and cycloblastin (AC):
ejection fraction >= 50% by multigated acquisition scan (MUGA) or echocardiogram
- Patients must sign informed consent
Exclusion Criteria:
- Concurrent administration of any other investigational agent(s)
- Prior high-dose therapy requiring hematopoietic stem cell transplantation
- Prior anti-cancer treatments involving radioactive pharmaceuticals
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ABT-888 and/or cyclophosphamide
- Patients receiving any medications or substances that are strong inhibitors or strong
inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP 3A4),
cytochrome P450, family 2, subfamily B, polypeptide 6 (2B6), cytochrome P450, family
2, subfamily C, polypeptide 9 (2C9) or cytochrome P450, family 2, subfamily C,
polypeptide 19 (2C19) are prohibited; at the time of screening, if the patient is
currently receiving any of the listed prohibited medication(s), the medication(s) must
be discontinued for a period of no less than 7 days prior to administration of the
first dose of study medication in order for the patient to meet study eligibility
except for the following substance where the washout should be 6 months: amiodarone
- 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; New York Heart Association (NYHA) grade II or greater congestive
heart failure
- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with ABT-888; these potential risks may also apply to other
agents used in this study
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible; appropriate studies will be undertaken in patients receiving
combination antiretroviral therapy when indicated; NOTE: HIV seropositive patients not
receiving combination antiretroviral therapy who have cluster of differentiation (CD)4
cells >= 350/mm^3, no opportunistic infections and meet all eligibility criteria may
participate in this study
- Any condition (e.g., gastrointestinal tract disease resulting in an inability to take
oral medication or a requirement for IV alimentation, prior surgical procedures
affecting absorption, or active peptic ulcer disease) that impairs their ability to
swallow and retain ABT-888 capsules
- Patients with gastrointestinal conditions that might predispose for drug
intolerability or poor drug absorption (e.g., inability to take oral medication or a
requirement for IV alimentation, prior surgical procedures affecting absorption,
malabsorption syndrome, active peptic ulcer disease) are excluded; subjects with
ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel
obstruction are also excluded
- Patients with active central nervous system (CNS) metastases are excluded
- Patients with CNS metastases that have been treated must be off steroid treatment
for > 3 months, be asymptomatic and off steroid treatment prior to study
enrollment
- Patients that have symptoms to suggest CNS metastases should have a brain
magnetic resonance imaging (MRI) within 28 days of enrollment to confirm the
absence of CNS metastases; contrast computed tomography (CT) is acceptable for
patients who are unable to undergo a brain MRI
- Patients with active seizure or a history of active seizure
- Any other medical, social, or psychological condition that may significantly affect
safety and/or compliance
- Patients enrolled in a group where treatment is AC: prior doxorubicin exposure of >
300 mg/m^2 or equivalent anthracycline exposure (i.e., epirubicin dose > 540 mg/m^2)
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