Beta-lapachone Prodrug ARQ 761 and Combination Chemotherapy in Treating Patients with Pancreatic Cancer That Is Metastatic, Recurrent, or Cannot Be Removed by Surgery

Inclusion Criteria

• Subjects must have a histologically or cytologically confirmed pancreatic adenocarcinoma that is metastatic, unresectable, or recurrent
• Has received at most 1 line of prior non-gemcitabine chemotherapy for metastatic/unresectable disease * Prior adjuvant gemcitabine, if completed more than 12 months prior to enrollment is not considered as prior line of therapy * Radiosensitizing chemotherapy will not be considered a prior line of therapy
• Chemotherapy: at least 2 weeks since prior cytotoxic chemotherapy
• Molecular targeted agents including monoclonal antibodies and tyrosine kinase inhibitors: at least two weeks since last therapy
• Radiotherapy: at least 3 weeks since most recent radiotherapy; prior radiated lesions will not be evaluable unless there is documented progression post therapy; palliative radiotherapy to localized painful lesions is acceptable when the patient is on study: at least one week after completion of radiation therapy (RT) and recovery from associated toxicities before restarting ARQ 761; irradiated lesions will not be evaluable for response
• Other investigational therapy: at least two weeks since any other investigational therapy
• Concurrent therapy: no other concurrent anticancer or investigational therapy permitted except as noted above
• Measurable disease is required per Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Anticipated life expectancy >= three months
• Central venous access, such as a Portacath or Hickman Line
• Subjects must have verbal or documented acknowledgement of availability of unstained slides or paraffin block tissue from archived tumor specimen; if not available the patient will undergo a fresh biopsy
• Hemoglobin >= 10 g/dL; subjects may be transfused packed red blood cells (PRBCs) up to 1 week prior to when enrollment labs are drawn; on study, transfusions may be given as clinically indicated (within 14 days prior to registration)
• Absolute neutrophil count (ANC) >= 1,500/uL (within 14 days prior to registration)
• Platelets >= 100,000/uL (within 14 days prior to registration)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) & alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 institutional ULN in subjects without known liver metastasis; =< 5 x institutional ULN in subjects with known liver metastasis (within 14 days prior to registration)
• Serum creatinine =< 1.5 mg/dL (within 14 days prior to registration)
• Subjects must be recovered from any toxicity related to prior anti-neoplastic therapy (to grade < 1); subjects with Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or less sensory neuropathy or any grade alopecia are eligible
• 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, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

Exclusion Criteria

• Subjects receiving any other investigational agents
• Subjects with known untreated brain metastases; subjects with known, treated brain metastases must be stable with no symptoms for four weeks after completion of that treatment, with image documentation required, and must either be off steroids or on a stable dose of steroids for at least two weeks prior to protocol enrollment; subjects with known leptomeningeal metastases are excluded, even if adequately treated; subjects without known brain metastases do not require radiologic imaging prior to enrollment
• Subjects receiving the following hepatic enzyme-inducing anti-seizure drugs (“EIASD”); for example: * Carbamazepine * Oxcarbazepine * Phenytoin * Fosphenytoin * Phenobarbital * Primidone
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
• Any condition that confounds the ability to interpret data from the study
• Unwillingness or inability to comply with study procedures