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

NCT ID: NCT02631590

Last Updated: 2021-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-05
• Study Completion Date: 2021-03-05

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.

Conditions

Biliary Carcinoma; Gall Bladder Carcinoma; Cholangiocarcinoma; Gastrointestinal Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Cisplatin administered once as intravenous (IV) infusion over 60 minutes. Treatment is on Days 1 and 8 every 21 days.

Gemcitabine

Intervention Type: DRUG

Gemcitabine administered as 30-min IV infusion. Treatment is on Days 1 and 8 every 21 days.

Copanlisib

Intervention Type: DRUG

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.

Interventions

Cisplatin

Cisplatin administered once as intravenous (IV) infusion over 60 minutes. Treatment is on Days 1 and 8 every 21 days.

Intervention Type: DRUG

Gemcitabine

Gemcitabine administered as 30-min IV infusion. Treatment is on Days 1 and 8 every 21 days.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Platinol; Gemzar; BAY 80-6946

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard D. Kim, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

References

Tan ES, Cao B, Kim J, Al-Toubah TE, Mehta R, Centeno BA, Kim RD. Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers. Cancer. 2021 Apr 15;127(8):1293-1300. doi: 10.1002/cncr.33364. Epub 2020 Dec 8.

Reference Type: DERIVED

PMID: 33289918 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MCC-18435

Identifier Type: -

Identifier Source: org_study_id