Presence of an unresectable liver mass consistent with cholangiocarcinoma, for which treatment with gemcitabine plus cisplatin is intended.
A history of prior systemic treatment with gemcitabine or cisplatin. At least six months must have elapsed if gemcitabine or cisplatin was administered in an adjuvant treatment setting.
Known hypersensitivity to gemcitabine, azacytidine or cytosine arabinoside
Patient must have not received gemcitabine, oxaliplatin and/or paclitaxel chemotherapy agents
Patients who have received gemcitabine, oxaliplatin and/or paclitaxel are excluded from this study
No prior chemotherapy for locally advanced or metastatic pancreatic cancer\r\n* Patients are eligible if they received adjuvant treatment after surgical resection with single-agent gemcitabine or gemcitabine/capecitabine or -fluorouracil/leucovorin that was completed >  months before enrollment; similarly, adjuvant radiation +/- chemosensitization with -fluorouracil, capecitabine, or gemcitabine is allowed if completed >  months before enrollment
For Part D dose confirmation: All participants must have histological evidence of cholangiocarcinoma and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received > line of prior systemic therapy for metastatic or resectable disease (that is, participants may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease).
SAFETY RUN-IN: Patients are candidates for chemotherapy with carboplatin and gemcitabine
SAFETY RUN-IN: Patients who received prior therapy using carboplatin/gemcitabine within  months prior to enrollment or subjects whose tumor progressed while on treatment with carboplatin or cisplatin
RANDOMIZED PHASE II CLINICAL TRIAL: Patients who received prior therapy using carboplatin/gemcitabine within  months prior to their enrollment or subjects whose tumor progressed while on treatment with carboplatin or cisplatin
Radiosensitizing chemotherapy (taxol [paclitaxel], taxotere [docetaxel], cisplatin, gemcitabine [gemcitabine hydrochloride], -fluorouracil [fluorouracil]) given within one week of radiation treatment
Cohorts -: Have previously received all of the following agents at any time in the platinum-resistant setting: gemcitabine, pegylated liposomal doxorubicin, and paclitaxel.
Patients who have previously received gemcitabine plus oxaliplatin therapy
History of, or known, hypersensitivity to gemcitabine or platinum-containing compounds.
Prior treatment with gemcitabine or platinum-containing compounds, including in the adjuvant setting.
Prior therapy: No line limit but no more than  prior regimens in the platinum resistant setting; no prior treatment targeting the ATR/checkpoint kinase  (CHK) pathway and no prior gemcitabine as single agent; hormonal therapies immunotherapy, and antiangiogenic therapies (as single agents) do not count as lines; poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP)-inhibitors count as a line of therapy unless given in the maintenance setting; PARP-inhibitors given as maintenance after platinum therapy do not count as a line of therapy; prior carboplatin/gemcitabine is allowed provided that there was no disease progression within  months after completion of the carboplatin/gemcitabine regimen; subjects may begin protocol treatment at least  weeks or  half-lives, whichever is shorter, after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible
Must not have previously received chemotherapy or any investigational agent for the treatment of PDAC. A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed for as long as last dose was administered >  months prior to randomization and no lingering toxicities are present.
A fluoropyrimidine or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed for as long as last dose was administered >  months prior to randomization.
Previous treatment with gemcitabine
In the opinion of the treating investigator, the patient must be a candidate to receive gemcitabine/cisplatin treatment
Patients must not be known to have hypersensitivity to cisplatin, gemcitabine, or celecoxib
Gemcitabine + nb-paclitaxel
. Gy (. Gy per fraction) with concurrent gemcitabine, capecitabine, or infusional -fluorouracil
The patient has undergone at least one prior, but no more than  prior standard, therapies for pancreatic cancer.If the patient has had prior gemcitabine treatment, the last date of gemcitabine administration-should be >  months prior to screening for the study. All patients who have previously received gemcitabine should be discussed with the medical monitor during screening
Have received prior cisplatin and gemcitabine concomitantly within the last  months or are refractory to cisplatin and gemcitabine.
Have known hypersensitivity to platinum compounds or gemcitabine.
For phase , prior intravesical treatment with nab-rapamycin or gemcitabine is not allowed
Known severe hypersensitivity to gemcitabine
Histologically or cytologically confirmed grade  or  soft tissue sarcoma that is unresectable or metastatic that would be standardly treated with gemcitabine or gemcitabine and docetaxel; prior surgery for primary or metastatic disease after chemotherapy following a response is allowed
For patients selecting vinorelbine or gemcitabine as the TPC agent, patients may not receive yellow fever vaccine in the  days prior to randomization.
Prior treatment with cisplatin and/or gemcitabine
Have documented radiographic progression to or documented intolerance of first line systemic chemotherapy which included either gemcitabine or fluorouracil (-FU) based regimen (including capecitabine)
Previous cytotoxic chemotherapy including cisplatin, carboplatin, oxaliplatin, etoposide, docetaxel, cabazitaxel, and gemcitabine is allowed, up to  prior regimens
Prior therapy with single-agent gemcitabine.
Prior history of hypersensitivity to gemcitabine.
Disease must be refractory to or intolerant of at least first-line chemotherapy which contains -fluorouracil or gemcitabine
To commence first-line standard nab-paclitaxel and gemcitabine chemotherapy, or gemcitabine alone, (per standard of care according to the approved prescribing schedule), within  to  days post enrolment, with OncoSil implantation to occur during the fourth (th) week of the first chemotherapy cycle
Eligible for one of the chemotherapy options listed as TPC (Eribulin, capecitabine, gemcitabine, or vinorelbine) as per investigator assessment.
Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study
Patients who were intolerant of a gemcitabine containing regimen.
Patients must have received  line of prior systemic therapy for metastatic or resectable disease (i.e. patients may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease)
Prior decitabine for the treatment of this cancer; patients with previous exposure to therapy with gemcitabine are allowed in the study
History of allergy or hypersensitivity to albumin-bound paclitaxel, or gemcitabine
Patients who have been off of FOLFIRINOX or gemcitabine/abraxane therapy for more than  days prior to treatment on study
Patients who have had more than one line of chemotherapy for LAPC (other than the - cycles of FOLFIRINOX or gemcitabine/abraxane based chemotherapy); patients will be allowed to switch between FOLFIRINOX and gemcitabine/abraxane due to intolerance, but cannot have switched chemotherapy regimens due to radiographic or clinical disease progression
Patients who have only received single agent gemcitabine chemotherapy; abraxane component may be reduced or modified but must be included for a minimum of two cycles
Must have received at least one regimen containing gemcitabine chemotherapy
Patients with a known hypersensitivity to gemcitabine (Arm B only)
Intolerance of protocol agents as follows:\r\n* Known or presumed intolerance of gemcitabine, vorinostat or sorafenib\r\n* Experienced any of the following toxicities with prior gemcitabine administration (if given): capillary leak syndrome, posterior reversible encephalopathy, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, unexplained dyspnea or other evidence of severe pulmonary toxicity, or severe hepatic toxicity
Patients previously treated with gemcitabine or Abraxane
Arms E: previously treated with and progressed on gemcitabine-containing therapy
Known hypersensitivity or infusion reaction to cisplatin and gemcitabine
Patients with known hypersensitivity to gemcitabine or docetaxel
Disease progression during or after treatment with gemcitabine (alone or in combination with other agents; at regular, not radiosensitizing, doses)
Patients who have received the combination of gemcitabine and docetaxel in the metastatic setting are excluded
Use of concurrent gemcitabine-based chemotherapy during radiotherapy
Patient must have not received gemcitabine, oxaliplatin and/or paclitaxel chemotherapy agents
Patients who have received gemcitabine, oxaliplatin and/or paclitaxel are excluded from this study
Arm C eligible for treatment with one of the following standard, every  week, platinum-based salvage regimens (with or without monoclonal antibody as appropriate for the disease):\r\n* Ifosfamide/carboplatin/etoposide (ICE) or rituximab/ifosfamide/carboplatin/etoposide (RICE);\r\n* Cisplatin, cytarabine (cytosine arabinoside), dexamethasone (DHAP) or rituximab, cisplatin, cytosine arabinoside, dexamethasone (RDHAP);\r\n* Gemcitabine hydrochloride (gemcitabine), dexamethasone, cisplatin (GDP) or rituximab, gemcitabine, dexamethasone, cisplatin (RGDP);\r\n* Gemcitabine and oxaliplatin (GemOx) or rituximab, gemcitabine and oxaliplatin (RGemOx);\r\n* Oxaliplatin, cytosine arabinoside, dexamethasone (OAD) or rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD)
Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or -FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least  months have elapsed since completion of the last dose and no lingering toxicities are present.
History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-) or drugs chemically-related to gemcitabine.
Cohort  (MTD) only: patient willing to undergo muscle biopsies at baseline and after  to  days of disulfiram/gemcitabine or gemcitabine/placebo therapy as required by the protocol
Prior exposure to gemcitabine
Have not been treated with gemcitabine in the metastatic setting
Prior treatment with gemcitabine alone or -fluorouracil with radiation as an adjuvant therapy will be allowed; patient should not have received gemcitabine within  months of starting the study treatment; -flourouracil or radiation treatment should be received more than  weeks prior to receiving the study drug
Patients may have received prior chemotherapy for advanced disease as long as it did not include gemcitabine; if patients received prior adjuvant therapy including gemcitabine, patients must be >  months from the last dose of gemcitabine; patients must have recovered from side effects of prior therapy to grade =<  as measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) .
Patients must not be known to have hypersensitivity to cisplatin, gemcitabine (gemcitabine hydrochloride), doxorubicin (doxorubicin hydrochloride), vinblastine (vinblastine sulfate), methotrexate or filgrastim/pegfilgrastim
Not a candidate for treatment with at least  of the treatments of protocol-specific physician's choice (ie, capecitabine, eribulin, gemcitabine, vinorelbine)
Patient who have had previous treatment with pazopanib or with weekly gemcitabine for recurrent or persistent disease
Has a history of severe hypersensitivity reaction (e.g. generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to pembrolizumab, gemcitabine, carboplatin, or cisplatin or their analogs and/or to any of their excipients.
Patients who previously received gemcitabine for the treatment of recurrent disease
Have received Gemcitabine for palliative treatment or progressed while receiving it or is within  months of completion in the adjuvant setting.
Have a known history of HIV are excluded due to the possibility that Gemcitabine or NPC-C(NEO-) may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to Gemcitabine or NPC-C(NEO-).
Patients who have had prior therapy with docetaxel, gemcitabine hydrochloride, or doxorubicin hydrochloride at any time in their history
Participant for whom treatment with monotherapy chemotherapy such as gemcitabine or capecitabine is a reasonable choice.
Have a known hypersensitivity to investigator's choice of standard of care (gemcitabine or capecitabine).
Patients who received Gemcitabine-based therapy in an adjuvant setting will be allowed to be enrolled on Arm A of the trial (Gemcitabine with nab-Paclitaxel) as long as their last Gemcitabine administration was at least  months prior to the first dose of BBI.
For patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel) a. Known hypersensitivity to Gemcitabine or taxanes. i. Patients with history of Gemcitabine toxicity in the adjuvant setting requiring more than  dose level reduction are excluded. b. Significant cardiac disease, including the following: unstable angina, New York Heart Association class III-IV congestive heart failure, myocardial infarction within six months prior to study enrollment. c. History of hemolytic-uremic syndrome. d. History of posterior reversible encephalopathy syndrome. e. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C. f. History of active Peripheral Artery Disease (treated peripheral artery disease that is stable for at least  months is allowed).
Patients must not have a history of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
Urothelial cancer arising in the bladder, renal pelvis, ureter or urethra that has progressed during or following at least  and up to  prior systemic treatments for unresectable locally advanced or metastatic disease (includes anti-PD-L,anti-PD-, but excludes other experimental therapies). Patients must have received at least one platinum-containing regimen (e.g., gemcitabine/cisplatin [GC], dose-dense methotrexate/vinblastine/doxorubicin/cisplatin [DDMVAC], or carboplatinum/gemcitabine). No more than  prior systemic regimens allowed.
History of needing to permanently discontinue prior gemcitabine/ cisplatin regimen for reasons other than progression (i.e. toxicity)
For stratum B patients must have received prior anthracycline-based therapy (or have a contraindication to receiving this treatment) and must not have received prior gemcitabine (gemcitabine hydrochloride)
Patients who have received prior non-gemcitabine-based systemic chemotherapy for metastatic disease or those who are beyond  months of exposure to gemcitabine-based chemotherapy regimen are allowed
Patients may have received prior adjuvant chemotherapy with gemcitabine with or without cisplatin, as long as  months have elapsed since last treatment.
=<  prior chemotherapies in the metastatic setting; prior anthracycline, taxane, gemcitabine, and anti-HER agents (i.e. trastuzumab, pertuzumab, lapatinib, neratinib, TDM-, etc.) are allowed; if patients received prior gemcitabine, it could not have been combined with pertuzumab; patients should have progression of disease on current therapy
Serious underlying lung function abnormality due to the risk of fatal pneumonitis that was caused by the combination of Abraxane and gemcitabine
Cholangiocarcinoma subjects must have progressed following gemcitabine-based regimen.
Patients with advanced breast cancer who have received platinum therapy (e.g. carboplatin or cisplatin) and/or gemcitabine therapy for metastatic disease are excluded (platinum-based therapy and/or gemcitabine in the adjuvant or neoadjuvant setting is allowed)
Ovarian cancer patients who have received prior gemcitabine therapy are ineligible; (prior carboplatin therapy is allowed)
Any number of prior chemotherapy regimens; up to two prior chemotherapy regimens in the palliative setting will be allowed in the expansion cohort; prior gemcitabine-based regimens in the palliative setting are permitted if no evidence of progression on therapy or at least  months after discontinuation of gemcitabine-based treatment; prior gemcitabine in the adjuvant setting is permitted if last treatment was greater than  months prior to registration
Known or suspected allergy to gemcitabine or cisplatin
Any concern for hypersensitivity to pazopanib, gemcitabine or docetaxel
No prior treatment with bendamustine; prior therapy with gemcitabine is permitted
Prior systemic therapy for advanced pancreas cancer with gemcitabine is prohibited; prior gemcitabine with radiotherapy for localized pancreas cancer is allowed provided disease is present outside of the radiated field; prior gemcitabine as adjuvant therapy to surgical resection is allowed provided  months or greater has elapsed between the last dose of gemcitabine and the detection of recurrent disease
EXPANSION COHORT ONLY: Previously treated with at least one and not more than  lines of systemic chemotherapy including at least one of the following: a platinum agent, a taxane, or gemcitabine
History of hypersensitivity to gemcitabine
Prior treatment with gemcitabine
Subject must have received no prior therapy for the treatment of metastatic disease. Prior treatment with -FU or gemcitabine administered as a radiation sensitizer during and up to  weeks after radiation therapy is allowed. If a subject received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least  months after completing the last dose of gemcitabine.
Radiosensitizing doses of gemcitabine if relapse occurred at least  months after completion of gemcitabine;
Received gemcitabine administered at a minimum dose of  mg/m per week in the first cycle of treatment
Progressed while receiving this gemcitabine regimen or within  months of completing gemcitabine
Prior first-line chemotherapy must have consisted of at least  cycles and no more than  cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin
Prior treatment with albumin-bound paclitaxel or gemcitabine
Patients with a diagnosis of advanced unresectable non-hematological malignancy that has no known standard of care or for which the use of gemcitabine plus cisplatin constitutes a reasonable option
Known inability to undergo neoadjuvant gemcitabine and cisplatin combination treatment due to pre-existing medical conditions in the opinion of the treating physician or investigator
Prior systemic therapy with a gemcitabine containing regimen
Known hypersensitivity to gemcitabine
A single course of gemcitabine and/or docetaxel as adjuvant therapy that was completed at least  months prior to planned first dose
History of prior significant toxicity from a same class of agents as GDC- or gemcitabine requiring discontinuation of treatment
Any contraindication to gemcitabine therapy
Part E - Diagnosed with cholangiocarcinoma, either intrahepatic or extrahepatic, that is unresectable, recurrent, or metastatic. Participants must not have received prior systemic front line therapy for metastatic or resectable disease (i.e. participants may have received adjuvant gemcitabine but have not yet received gemcitabine/cisplatin for recurrent metastatic disease). Participants must be, in the opinion of the investigator, an appropriate candidate for experimental therapy. Participants should be evaluated for the need to undergo biliary drainage by stent placement prior to study participation. Participants should have adequate biliary drainage with no unresolved biliary obstruction.
Histological confirmation of urothelial carcinoma and high risk residual disease after neoadjuvant chemotherapy (NAC) and cystectomy as defined by post-operative pathological pT or N- disease, or progressive disease during NAC (NAC include methotrexate, vinblastin, doxorubicin and cisplatin [MVAC], dose dense MVAC, gemcitabine cisplatin, or gemcitabine carboplatin); minor histologic variants (< %) are acceptable if urothelial carcinoma is predominant variant
Prior chemotherapies are permitted, except with prior treatments with taxanes, vinca alcaloids, gemcitabine, eribulin, ixabepilone, platinum drugs
Previous exposure to gemcitabine instillations.
Patients with active non-hematologic cancer:\r\n* The patients have previously received a chemotherapy regimen including one or more of the following agents:\r\n** Nucleoside analogue, including gemcitabine and fluorouracil\r\n** Carboplatin or cisplatin\r\n** Anthracycline\r\n** Alkylating agent\r\n** Other chemotherapy agents with thrombocytopenia as known common toxicity
Minocycline Trial only: patients with a pathological or clinical diagnosis of pancreatic cancer and beginning or continuing FOLFIRINOX or gemcitabine-based chemotherapy
Prior treatment with gemcitabine-containing therapy for advanced disease (adjuvant therapy is allowed, provided not more than six cycles were administered and relapse occurred more than six months after the last drug administration), and/or:
Patients who have previously discontinued gemcitabine-containing regimens due to gemcitabine-related toxicity.