Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase Inhi... | NCT01460537

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment A: Gemcitabine-Copanlisib	Experimental	The treatment consists of repetitive cycles, each over 28 days. Treatment continues until disease progression or dose limiting toxicity. If gemcitabine is discontinued for toxicity, Copanlisib may be continued at the discretion of the Investigator if a clinical benefit (response or stable disease for 3 months) is noted. - Hour 0 to 0.5: Gemcitabine (1000 mg/m2 as 30-minute IV infusion) on Days 1, 8 and 15 every 28 days - Hour 1.5 to 2.5: BAY80-6946 (starting dose = 0.6 mg/kg as 60-minute IV infusion, starting 1 hour post completion of gemcitabine infusion) on Days 1, 8 and 15 every 28 days	Drug: Gemcitabine Drug: BAY80-6946
Treatment B: Cisplatin-Gemcitabine-Copanlisib	Experimental	Treatment consists of repetitive 21 day cycles for a maximum of 8 cycles. Treatment continues until disease progression, DLT or completion of 8 cycles. After 8 cycles, gemcitabine and Copanlisib, without cisplatin, may continue at the discretion of the Investigator until disease progression or DLT if a clinical benefit is noted (response or stable disease for 3 months). Treatment is administered on Days 1 and 8 every 21 days as follows: - Hour 0 to 1: Cisplatin IV infusion over 60 min (One liter of 0.9% NaCl including 25 mg/m2 cisplatin, 20 mmol of potassium chloride, and 8 mmol of magnesium sulfate) - Hour 1 to 1.5: IV infusion of 500 ml of 0.9% NaCl over 30 min - Hour 1.5 to 2: Gemcitabine (1000 mg/m2 as 30 min IV infusion) - Hour 3 to 4: Copanlisib IV infusion at the MTD determined in Treatment A over 60 min. [If Treatment A MTD is not tolerable, further subject enrollment will begin at one Copanlisib Dose Level lower with the cisplatin-gemcitabine doses remaining constant.]	Drug: Gemcitabine Drug: Cisplatin Drug: NaCl Drug: BAY80-6964 fixed dose

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Gemcitabine	Drug	Gemcitabine 1000mg/m2 as 30-minutes IV infusion	Treatment A: Gemcitabine-Copanlisib Treatment B: Cisplatin-Gemcitabine-Copanlisib

Measure	Description	Time Frame
Adverse event collection		Up to 3 years or longer if indicated
Maximum tolerated dose, measured by adverse event profile		Up to 3 years or longer if indicated

Measure	Description	Time Frame
Maximum drug concentration in plasma (Cmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine		Approximately 18 months
The time of the maximum concentration (Tmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine		Approximately 18 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects, at least 18 years of age, with advanced or refractory solid tumors in whom gemcitabine (Treatment A) or cisplatin plus gemcitabine (Treatment B) is appropriate medical therapy as determined by the treating physician
Histological or cytological documentation of non-hematologic, malignant solid tumor, excluding primary brain or spinal tumors, with no current involvement in the CNS
At least one measurable lesion or evaluable disease, as per RECIST 1.1
Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0 or 1
Life expectancy of at least 12 weeks
Alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN; ≤5 x ULN for subjects with liver involvement with cancer)
Aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN for subjects with liver involvement with cancer)
Total bilirubin ≤ 2.0 x ULN
Serum creatinine ≤ 1.5 x ULN
Prothrombin time-international normalized ratio/partial thromboplastin time (PT-INR/PTT) < 1.5 x ULN (Subjects who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists). Low-dose aspirin is permitted (≤ 100 mg daily).

Exclusion Criteria:

History of cardiac disease congestive; congestive heart failure > New York Heart Association functional classification system (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy
Current diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as consistent fasting blood glucose > 125 mg/dL) or HgBA1c ≥ 7%
Use of systemic corticosteroids within 2 weeks of the start of study treatment (topical or inhaled steroids are permitted). Single doses of systemic corticosteroids given as premedication for procedures or non-study drugs may be administered up to 24 hours of first dosing of Copanlisib.
Poorly controlled hypertension, defined as systolic blood pressure (BP) > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
Poorly controlled seizure disorder
Subjects undergoing renal dialysis
Use of strong inhibitors of CYP3A4 (eg, ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir, nefazodone and saquinavir) and strong inducers of CYP3A4 (eg, rifampin) are not permitted from Day -14 of Cycle 1 and for the duration of the study.
Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of first study treatment
Hormonal therapy during the study or within 2 weeks of first study treatment.
Bisphosphonate therapy during the first 2 cycles of treatment
Biological response modifiers, such as granulocyte colony stimulating factor (G-CSF) within 4 weeks of first study treatment
Radiotherapy to target lesions during study or within 4 weeks of first study treatment
Known hypersensitivity to the study drugs or active substances or excipients of the preparations
Use of St John's Wort is prohibited from Day -14 and for the duration of the study

Facility	Status	City	State	ZIP	Country	Contacts
		Tampa	Florida	33612	United States

ID	Term
D000093542	Gemcitabine
D002945	Cisplatin

ID	Term
D006571	Heterocyclic Compounds
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds