Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma
Condition: Biliary Carcinoma; Gall Bladder Carcinoma; Cholangiocarcinoma; Gastrointestinal Tumor
MeSH terms: Carcinoma; Cholangiocarcinoma; Urinary Bladder Neoplasms; Digestive System Neoplasms; Gastrointestinal Neoplasms
Intervention: Cisplatin; Gemcitabine; Copanlisib
Intervention description: Cisplatin administered once as intravenous (IV) infusion over 60 minutes. Treatment is on Days 1 and 8 every 21 days.; Gemcitabine administered as 30-min IV infusion. Treatment is on Days 1 and 8 every 21 days.; Experimental Drug: Copanlisib administered as an IV over 60-minutes beginning 1 hour after completing gemcitabine infusion. Treatment is on Days 1 and 8 every 21 days.
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: intra-hepatic biliary system; extra-hepatic biliary system; gall bladder; advanced biliary cancer; unresectable; locally advanced; metastatic disease

Summary:

      The purpose of this study is to see if an experimental drug, called copanlisib is effective
      and safe in treating adult participants with cholangiocarcinoma, when used in combination
      with gemcitabine and cisplatin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have histologically or cytologically documented carcinoma primary to the intra-
             or extra-hepatic biliary system or gall bladder with clinical and/or radiologic
             evidence of unresectable, locally advanced or metastatic disease. Patients with
             ampullary carcinoma are not eligible.

          -  Must not have received any systemic chemotherapy for advanced biliary cancer.

          -  Patients who received adjuvant chemotherapy plus or minus radiation and had evidence
             of disease recurrence within 6 months of completion of the adjuvant treatment are not
             eligible. If patients received adjuvant treatment and had disease recurrence after 6
             months, patients will be eligible.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0 or 1.

          -  Must have radiographic measurable disease.

          -  Life expectancy of at least 12 weeks (3 months).

          -  For patients who have received prior radiation, cryotherapy, radiofrequency ablation,
             therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic
             therapy, the following criteria must be met: 28 days have elapsed since that therapy;
             Lesions that have not been treated with local therapy must be present and measureable.

          -  Adequate bone marrow, liver and liver function.

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of study drug. Men and women of childbearing
             potential must agree to use adequate contraception beginning at the signing of the
             Informed Consent Form (ICF) until at least 3 months after the last dose of study drug.

          -  Must be able to swallow and retain oral medication.

          -  Availability of archival tumor tissue for biomarkers analysis (minimum of 10 unstained
             slides are optional). Specimen from primary site will be allowed.

        Exclusion Criteria:

          -  Previous or concurrent cancer within 3 years prior to treatment start except for
             curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial
             bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades
             lamina propria)].

          -  Congestive heart failure > New York Heart Association (NYHA) class 2.

          -  Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
             months).

          -  Myocardial infarction less than 6 months before study enrollment

          -  Uncontrolled hypertension (blood pressure ≥ 150/90 mmHg despite optimal medical
             management).

          -  Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within the 6 months before enrollment.

          -  Non-healing wound, ulcer, or bone fracture.

          -  Active clinically serious infections (> Common Terminology Criteria for Adverse Events
             (CTCAE) grade 2).

          -  Known history of human immunodeficiency virus (HIV) infection.

          -  Known active Hepatitis B or C.

          -  A seizure disorder requiring medication.

          -  Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE
             Grade 3 within 4 weeks of start of study enrollment.

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the patient's participation in the study or evaluation of the study results.

          -  Known hypersensitivity to any of the test drugs, test drug classes, or excipients in
             the formulation.

          -  History or concurrent condition of interstitial lung disease of any grade or severely
             impaired pulmonary function.

          -  Unresolved toxicity higher than CTCAE grade 1 attributed to any prior
             therapy/procedure excluding alopecia.

          -  HbA1c >8.5% or fasting plasma glucose > 160 mg/dL at screening.

          -  Concurrent diagnosis of pheochromocytoma.

          -  Women who are pregnant or breast feeding.

          -  Any illness or medical conditions that are unstable or could jeopardize the safety of
             the patient and his/her compliance in the study.