Biliary Carcinoma, Cholangiocarcinoma, Gall Bladder Carcinoma, Gastrointestinal Tumor
Conditions
Keywords
intra-hepatic biliary system, extra-hepatic biliary system, gall bladder, advanced biliary cancer, unresectable, locally advanced, metastatic disease
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.
Interventions
DRUGCisplatin
Cisplatin administered once as intravenous (IV) infusion over 60 minutes. Treatment is on Days 1 and 8 every 21 days.
DRUGGemcitabine
Gemcitabine administered as 30-min IV infusion. Treatment is on Days 1 and 8 every 21 days.
DRUGCopanlisib
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.
Sponsors
Bayer
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 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
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 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. |
| Overall Survival (OS) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Cisplatin: Cisplatin administered once as intravenous (IV) infusion over 60 minutes. Treatment is on Days 1 and 8 every 21 days.
Gemcitabine: Gemcitabine administered as 30-min IV infusion. Treatment is on Days 1 and 8 every 21 days.
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. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Combination Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 24 |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 12 / 24 |
Outcome results
Primary
Progression Free Survival (PFS)
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.)
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Therapy | Progression Free Survival (PFS) | 6.2 months |
Secondary
Overall Survival (OS)
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.
Time frame: Up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Therapy | Overall Survival (OS) | 13.7 months |
Secondary
Response Rate
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.
Time frame: Up to 24 months
Population: Number of participants evaluable for response
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Therapy | Response Rate | Partial Response | 31.6 percentage of participants |
| Combination Therapy | Response Rate | Stable Disease | 57.9 percentage of participants |