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Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma

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ClinicalTrials.gov Identifier: NCT02631590
Recruitment Status : Recruiting
First Posted : December 16, 2015
Last Update Posted : May 11, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Biliary Carcinoma Gall Bladder Carcinoma Cholangiocarcinoma Gastrointestinal Tumor Drug: Cisplatin Drug: Gemcitabine Drug: Copanlisib Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma
Actual Study Start Date : June 28, 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Combination Therapy
Treatment Plan: Cisplatin (25 mg/m^2 ) + Gemcitabine (1000 mg/m^2) + copanlisib (60 mg) on days 1 and 8 with day 15 off to be administered on an every 21-days schedule.
Drug: Cisplatin
Cisplatin administered once as intravenous (IV) infusion over 60 minutes. Treatment is on Days 1 and 8 every 21 days.
Other Name: Platinol

Drug: Gemcitabine
Gemcitabine administered as 30-min IV infusion. Treatment is on Days 1 and 8 every 21 days.
Other Name: Gemzar

Drug: Copanlisib
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.
Other Name: BAY 80-6946




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 6 months ]
    PFS at six months. Response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). PFS will be calculated from study entry to documented disease progression, death from any cause, or date of last follow-up, whichever comes first. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.)


Secondary Outcome Measures :
  1. Response Rate [ Time Frame: Up to 24 months ]
    Complete Response + Partial Response according to RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  2. Overall Survival (OS) [ Time Frame: Up to 24 months ]
    The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02631590


Contacts
Contact: Richard D. Kim, M.D. 813-745-1277 richard.kim@moffitt.org

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Maria Martinez Jimenez    813-745-1946    maria.martinez@moffitt.org   
Contact: Richard D. Kim    813-745-1277    richard.kim@moffitt.org   
Principal Investigator: Richard D. Kim, M.D.         
Sub-Investigator: Rutika Mehta, M.D.         
Sub-Investigator: Dae Won Kim, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bayer
Investigators
Principal Investigator: Richard D. Kim, M.D. H. Lee Moffitt Cancer Center and Research Institute

Additional Information:
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT02631590     History of Changes
Other Study ID Numbers: MCC-18435
First Posted: December 16, 2015    Key Record Dates
Last Update Posted: May 11, 2018
Last Verified: May 2018

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
intra-hepatic biliary system
extra-hepatic biliary system
gall bladder
advanced biliary cancer
unresectable
locally advanced
metastatic disease

Additional relevant MeSH terms:
Cholangiocarcinoma
Carcinoma
Urinary Bladder Neoplasms
Digestive System Neoplasms
Gastrointestinal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs