Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase Inhibitor BAY80-6946 With Gemcitabine or Cisplatin Plus Gemcitabine in Patients With Advanced Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01460537
First received: September 15, 2011
Last updated: January 20, 2014
Last verified: January 2014

September 15, 2011
January 20, 2014
November 2011
July 2014   (final data collection date for primary outcome measure)
  • Adverse event collection [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose, measured by adverse event profile [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01460537 on ClinicalTrials.gov Archive Site
  • Maximum drug concentration in plasma (Cmax) of BAY80-6946 with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • The time of the maximum concentration (Tmax) of BAY80-6946 with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Area under the curve (AUC) of BAY80-6946 with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Area under the concentration time curve (AUC (0-tn)) of BAY80-6946 with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Half life (t1/2) of BAY80-6946 with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Biomarker evaluation including analysis of pathway activation in tumor tissue and blood/plasma [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: No ]
  • Tumor Response as measured by RECIST 1.1 criteria [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase Inhibitor BAY80-6946 With Gemcitabine or Cisplatin Plus Gemcitabine in Patients With Advanced Cancer
A Phase 1 Study of BAY80-6946 (Phosphatidylinositol-3 Kinase Inhibitor) in Combination With Gemcitabine (Treatment A) or Cisplatin Plus Gemcitabine (Treatment B) in Subjects With Advanced Solid Malignancy

This open label Phase I study involves treating subjects with advanced cancer with BAY80-6946 in combination with either gemcitabine or cisplatin plus gemcitabine. It will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of BAY80-6946 in combination with gemcitabine and BAY80-6946 in combination with cisplatin and gemcitabine. The trial will involve multiple participating sites from the US. Up to a maximum of 70 subjects will be enrolled in the study.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Neoplasms
  • Drug: Gemcitabine
    Gemcitabine 1000mg/m2 as 30-minutes IV infusion
  • Drug: BAY80-6946
    Escalated dose starting from 0.6 mg/kg in 100 mL of 0.9% NaCl as 60-minutes IV infusion
  • Drug: Cisplatin
    1 liter of 0.9% NaCl including 25 mg/m2 cisplatin, 20 mmol of potassium chloride, and 8 nmol of magnesium sulfate over 60 minutes
  • Drug: NaCl
    Infusion of 500 ml of 0.9% NaCl over 30-minutes
  • Drug: BAY80-6964 fixed dose
    BAY80-6946 IV infusion at the maximum tolerated dose determined in Treatment A over 60 min. [If Treatment A MTD is not tolerable, further subject enrollment will begin at one BAY80-6946 Dose Level lower with the cisplatin-gemcitabine doses remaining constant.]
  • Experimental: Treatment A: Gemcitabine-BAY80-6946

    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, BAY80-6946 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
    Interventions:
    • Drug: Gemcitabine
    • Drug: BAY80-6946
  • Experimental: Treatment B: Cisplatin-Gemcitabine-BAY80-6946
    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 BAY80-6946, 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: BAY80-6946 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 BAY80-6946 Dose Level lower with the cisplatin-gemcitabine doses remaining constant.]
    Interventions:
    • Drug: Gemcitabine
    • Drug: Cisplatin
    • Drug: NaCl
    • Drug: BAY80-6964 fixed dose
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
60
July 2014
July 2014   (final data collection date for primary outcome measure)

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 BAY 80-6946.
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01460537
12875
No
Bayer
Bayer
Not Provided
Study Director: Bayer Study Director Bayer
Bayer
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP