Trial record 1 of 448 for:    (Phosphatidylinositol-3 Kinase Inhibitor) in combination with Gemcitabine OR Cisplatin plus Gemcitabine.
Previous Study | Return to List | Next Study

Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase Inhibitor Copanlisib 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: June 16, 2014
Last verified: June 2014
  Purpose

This open label Phase I study involves treating subjects with advanced cancer with Copanlisib in combination with either gemcitabine or cisplatin plus gemcitabine. It will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Copanlisib in combination with gemcitabine and Copanlisib 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.


Condition Intervention Phase
Neoplasms
Drug: Gemcitabine
Drug: BAY80-6946
Drug: Cisplatin
Drug: NaCl
Drug: BAY80-6964 fixed dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Copanlisib(Phosphatidylinositol-3 Kinase Inhibitor) in Combination With Gemcitabine (Treatment A) or Cisplatin Plus Gemcitabine (Treatment B) in Subjects With Advanced Solid Malignancy

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Maximum drug concentration in plasma (Cmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • The time of the maximum concentration (Tmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Area under the curve (AUC) of Copanlisib 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 Copanlisib with gemcitabine or cisplatin plus gemcitabine [ Time Frame: Approximately 18 months ] [ Designated as safety issue: No ]
  • Half life (t1/2) of Copanlisib 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 ]

Enrollment: 50
Study Start Date: November 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A: Gemcitabine-Copanlisib
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
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
Experimental: Treatment B: Cisplatin-Gemcitabine-Copanlisib
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
Gemcitabine 1000mg/m2 as 30-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.]

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01460537

Locations
United States, Florida
Tampa, Florida, United States, 33612
United States, Minnesota
Rochester, Minnesota, United States, 55905
United States, North Carolina
Chapel Hill, North Carolina, United States, 27599-7305
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01460537     History of Changes
Other Study ID Numbers: 12875
Study First Received: September 15, 2011
Last Updated: June 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
phase I
phosphatidylinositol-3 kinase inhibitor
gemcitabine
cisplatin
maximum tolerated dose

Additional relevant MeSH terms:
Gemcitabine
Cisplatin
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014