NeoplasmsPhase 1NCT01460537
Phase 1 Study of PI3 (Phosphatidylinositol-3)-Kinase Inhibitor Copanlisib With Gemcitabine or Cisplatin Plus Gemcitabine in Patients With Advanced Cancer
A Phase 1 study testing Gemcitabine, BAY80-6946 and Cisplatin in people with Neoplasms, run by Bayer at 3 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Gemcitabine, BAY80-6946 and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 3 sitesUnited States
- Study dates
- 18 Nov 2011to 18 Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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).
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Study site
Chapel Hill, North Carolina, 27599-7305
Study site
Rochester, Minnesota, 55905
Study site
Tampa, Florida, 33612
About this study
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
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.
- Conditions
- Neoplasms
- Being tested
- Gemcitabine, BAY80-6946, Cisplatin, NaCl, BAY80-6964 fixed dose
- Keywords
- phase I, phosphatidylinositol-3 kinase inhibitor, gemcitabine, cisplatin, maximum tolerated dose
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Gemcitabine 1000mg/m2 as 30-minutes IV infusion
BAY80-6946Drug
Escalated dose starting from 0.6 mg/kg in 100 mL of 0.9% NaCl as 60-minutes IV infusion
CisplatinDrug
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
NaClDrug
Infusion of 500 ml of 0.9% NaCl over 30-minutes
BAY80-6964 fixed doseDrug
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.]
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: Gemcitabine-Copanlisib | Experimental | 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 Receives: Drug: Gemcitabine; Drug: BAY80-6946 |
| Treatment B: Cisplatin-Gemcitabine-Copanlisib | Experimental | 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.] Receives: Drug: Gemcitabine; Drug: Cisplatin; Drug: NaCl; Drug: BAY80-6964 fixed dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event collection
Measured: Up to 3 years or longer if indicated
Maximum tolerated dose, measured by adverse event profile
Measured: Up to 3 years or longer if indicated
Secondary outcomes (7)
Maximum drug concentration in plasma (Cmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Measured: Approximately 18 months
The time of the maximum concentration (Tmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Measured: Approximately 18 months
Area under the curve (AUC) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Measured: Approximately 18 months
Area under the concentration time curve (AUC (0-tn)) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Measured: Approximately 18 months
Half life (t1/2) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Measured: Approximately 18 months
Biomarker evaluation including analysis of pathway activation in tumor tissue and blood/plasma
Measured: Up to 3 years or longer if indicated
Tumor Response as measured by RECIST 1.1 criteria
Measured: Up to 3 years or longer if indicated
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2011 (estimated)
- Study start18 Nov 2011
- Primary completion20 Jul 2015
- Study completion18 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01460537
- Sponsor's protocol ID
- 12875
- Status last verified
- Oct 2017
- First submitted
- 15 Sep 2011
- Last updated
- 4 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01460537
- Acronym / sponsor ID
- 12875
- Conditions
- Neoplasms
- Keywords
- phase I, phosphatidylinositol-3 kinase inhibitor, gemcitabine, cisplatin, maximum tolerated dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2011 (actual)
- Primary completion
- 20 Jul 2015 (actual)
- Study completion
- 18 Dec 2015 (actual)
- First posted
- 27 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A: Gemcitabine-Copanlisib | Experimental | Drug: Gemcitabine, Drug: BAY80-6946The 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 |
| Treatment B: Cisplatin-Gemcitabine-Copanlisib | Experimental | Drug: Gemcitabine, Drug: Cisplatin, Drug: NaCl, Drug: BAY80-6964 fixed doseTreatment 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.] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineGemcitabine 1000mg/m2 as 30-minutes IV infusion | Drug | Treatment A: Gemcitabine-Copanlisib, Treatment B: Cisplatin-Gemcitabine-Copanlisib |
| BAY80-6946Escalated dose starting from 0.6 mg/kg in 100 mL of 0.9% NaCl as 60-minutes IV infusion | Drug | Treatment A: Gemcitabine-Copanlisib |
| Cisplatin1 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 | Treatment B: Cisplatin-Gemcitabine-Copanlisib |
| NaClInfusion of 500 ml of 0.9% NaCl over 30-minutes | Drug | Treatment B: Cisplatin-Gemcitabine-Copanlisib |
| BAY80-6964 fixed doseBAY80-6946 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.] | Drug | Treatment B: Cisplatin-Gemcitabine-Copanlisib |
Primary outcome
Adverse event collection
Time frame: Up to 3 years or longer if indicated
Maximum tolerated dose, measured by adverse event profile
Time frame: Up to 3 years or longer if indicated
7 secondary outcomes
Maximum drug concentration in plasma (Cmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Time frame: Approximately 18 months
The time of the maximum concentration (Tmax) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Time frame: Approximately 18 months
Area under the curve (AUC) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Time frame: Approximately 18 months
Area under the concentration time curve (AUC (0-tn)) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Time frame: Approximately 18 months
Half life (t1/2) of Copanlisib with gemcitabine or cisplatin plus gemcitabine
Time frame: Approximately 18 months
Biomarker evaluation including analysis of pathway activation in tumor tissue and blood/plasma
Time frame: Up to 3 years or longer if indicated
Tumor Response as measured by RECIST 1.1 criteria
Time frame: Up to 3 years or longer if indicated
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2017.
Related trials for Neoplasms
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gemcitabine, BAY80-6946 and Cisplatin in people with Neoplasms, run by Bayer at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse event collection (time frame: Up to 3 years or longer if indicated). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2017.