An Open-label Phase Ib/II Study of BAY 1000394 (Roniciclib) in Combination With Docetaxel in Second- or Third-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Primary Purpose
NSCLC (Non-Small Cell Lung Cancer)
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
BAY 1000394 (Roniciclib) in combination with docetaxel
Sponsored by
About this trial
This is an interventional treatment trial for NSCLC (Non-Small Cell Lung Cancer)
Eligibility Criteria
Inclusion Criteria:
Screening must be performed within 14 days prior to the first dose of study drug. Subjects are eligible for inclusion in this study if all of the following criteria are met:
- Histologically or cytologically confirmed stage IIIB or IV NSCLC Patients who received prior 1 or 2 lines of systemic anticancer therapy. For EGFR mutated or ALK rearranged patients, EGFR TKI or ALK inhibitor is also considered a line of systemic therapy
- Documented progressive disease after platinum-containing doublet chemotherapy (Platinum-containing chemotherapy given as an neoadjuvant/adjuvant chemotherapy, or definitive concurrent chemoradiotherapy within 6 months can be considered as one line of chemotherapy)
- For patients who showed non-progressive disease with 1st line platinum-doublet chemotherapy, continuation maintenance therapy is not considered a line of therapy, whereas switch maintenance therapy is considered another line of therapy.
- EGFR mutated or ALK rearranged patients can be eligible after one line of EGFR TKI or ALK inhibitor and platinum-doublet chemotherapy.
- Any prior systemic anticancer therapy must have been completed at least 3 weeks prior to initiation of study medication. Palliative radiation, whole brain radiotherapy (WBRT), or gamma knife surgery (GKS) for brain metastases must have been completed at least 2 weeks prior to initiation of study medication. Major or minor surgery must have been completed at least 4 or 2 weeks prior to initiation of study medication, respectively. Majority or minority of surgery can be decided at the investigator's discretion. Any acute toxicity must have recovered to Grade ≤ 1 (except alopecia).
- Male or female subjects aged ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements to be conducted within 14 days prior to the first dose of study drug:
- At least one measurable lesion based on RECIST 1.1
- Availability of tumor tissue for molecular analysis is not mandatory (presence of archival tissue or re-biopsy for acquisition of tumor tissue is strongly recommended)
Exclusion Criteria:
Subjects are to be excluded from the study if they display any of the following criteria:
- Prior radiotherapy (local palliative radiotherapy is permitted but must have occurred ≥2 weeks and subject must have no Grade 3 or 4 toxicities prior to first dose of study treatment; palliative is defined as not intended to cure but to relieve symptoms and reduce suffering)
- Eligibility for local therapy (surgery or radiotherapy)
- Previous treatment with any CDK inhibitors or docetaxel
- Current or ongoing administration of anticoagulation or antiplatelet therapy. However, use of low-dose aspirin (≤100 mg/day) and/or low-dose heparin is permitted unless it is being used for conditions other than cancer
- Known hypersensitivity to any of the study treatments or excipients of the preparations or any agent given in association with this study
- Previous deep vein thrombosis (within the last 6 months), arterial thrombotic events (including strokes), or pulmonary embolism
- History of cardiac disease: Congestive heart failure New York Heart Association (NYHA) Class III or IV angina (within past 6 months prior to study entry), myocardial infarction, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
- Active clinically serious infections of NCI-CTCAE v4.0 >Grade 2
- Known human immunodeficiency virus infection, active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
- Seizure disorder requiring therapy (such as steroids or anti-epileptics)
- Symptomatic metastatic brain or meningeal tumors, including those of the spinal cord, and including cases of neoplastic meningitis (also known as symptomatic carcinomatous meningitis or leptomeningeal carcinomatosis). However, after WBRT or GKS for symptomatic brain or leptomeningeal metastases, if subjects are stable for 2 weeks without steroid and the dosage of anti-convulsant is stable for 2 weeks, they are eligible. Asymptomatic central nervous system metastases are eligible if the subject has no abnormal findings on neurologic examination and is not receiving corticosteroid therapy to control symptoms.
- History of organ allograft
- Evidence or history of bleeding disorder, ie any hemorrhage / bleeding event of NCI-CTCAE v4.0 >Grade 2 within 4 weeks prior to the first dose of study treatment
- Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg despite optimal medical management)
- Serious, non-healing wound, ulcer, or bone fracture (bone fractures due to bone metastases are acceptable)
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Roniciclib with Docetaxel
Arm Description
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
Determination of the maximum tolerated dose (MTD) of BAY 1000394 (Roniciclib) in combination with docetaxel.
Dose-Limiting Toxicities (DLT)
Determination of the dose-limiting toxicities (DLT) of BAY 1000394 (Roniciclib) in combination with docetaxel.
Progression-Free Survival (PFS)
Evaluation of the progression-free survival (PFS) at 4 months by RECIST 1.1 criteria.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02522910
Brief Title
An Open-label Phase Ib/II Study of BAY 1000394 (Roniciclib) in Combination With Docetaxel in Second- or Third-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Official Title
An Open-label Phase Ib/II Study of BAY 1000394 (Roniciclib) in Combination With Docetaxel in Second- or Third-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Withdrawn
Study Start Date
August 2015 (undefined)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study part will be conducted in an open-label, non-randomized, Phase I conventional 3+3 dose-escalating design to define the safety, tolerability, pharmacokinetics, and MTD of BAY 1000394 (Roniciclib) given in a 3 days on / 4 days off schedule in combination with docetaxel in subjects with second- or third-line NSCLC.
Detailed Description
This study part will be conducted in an open-label, non-randomized, Phase I conventional 3+3 dose-escalating design to define the safety, tolerability, pharmacokinetics, and MTD of BAY 1000394 (Roniciclib) given in a 3 days on / 4 days off schedule in combination with docetaxel in subjects with second- or third-line NSCLC.
The number of subjects treated in the dose-escalation part depends on the number of dose- escalation or de-escalation steps needed to determine the MTD of BAY 1000394 (Roniciclib) in combination with docetaxel in this subject population.
Subjects treated at the recommended phase II dose level within the Phase Ib part of the study will be included in the response evaluation of the Phase II part.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NSCLC (Non-Small Cell Lung Cancer)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Roniciclib with Docetaxel
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BAY 1000394 (Roniciclib) in combination with docetaxel
Intervention Description
The study (Phase Ib part and Phase II part) will be conducted as a single center study. This study part will be conducted in an open-label, non-randomized, Phase I conventional 3+3 dose-escalating design to define the safety, tolerability, pharmacokinetics, and MTD of BAY 1000394 (Roniciclib) given in a 3 days on / 4 days off schedule in combination with docetaxel in subjects with second- or third-line NSCLC.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
Determination of the maximum tolerated dose (MTD) of BAY 1000394 (Roniciclib) in combination with docetaxel.
Time Frame
4 months after the study enrollment
Title
Dose-Limiting Toxicities (DLT)
Description
Determination of the dose-limiting toxicities (DLT) of BAY 1000394 (Roniciclib) in combination with docetaxel.
Time Frame
4 months after the study enrollment
Title
Progression-Free Survival (PFS)
Description
Evaluation of the progression-free survival (PFS) at 4 months by RECIST 1.1 criteria.
Time Frame
4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Screening must be performed within 14 days prior to the first dose of study drug. Subjects are eligible for inclusion in this study if all of the following criteria are met:
Histologically or cytologically confirmed stage IIIB or IV NSCLC Patients who received prior 1 or 2 lines of systemic anticancer therapy. For EGFR mutated or ALK rearranged patients, EGFR TKI or ALK inhibitor is also considered a line of systemic therapy
Documented progressive disease after platinum-containing doublet chemotherapy (Platinum-containing chemotherapy given as an neoadjuvant/adjuvant chemotherapy, or definitive concurrent chemoradiotherapy within 6 months can be considered as one line of chemotherapy)
For patients who showed non-progressive disease with 1st line platinum-doublet chemotherapy, continuation maintenance therapy is not considered a line of therapy, whereas switch maintenance therapy is considered another line of therapy.
EGFR mutated or ALK rearranged patients can be eligible after one line of EGFR TKI or ALK inhibitor and platinum-doublet chemotherapy.
Any prior systemic anticancer therapy must have been completed at least 3 weeks prior to initiation of study medication. Palliative radiation, whole brain radiotherapy (WBRT), or gamma knife surgery (GKS) for brain metastases must have been completed at least 2 weeks prior to initiation of study medication. Major or minor surgery must have been completed at least 4 or 2 weeks prior to initiation of study medication, respectively. Majority or minority of surgery can be decided at the investigator's discretion. Any acute toxicity must have recovered to Grade ≤ 1 (except alopecia).
Male or female subjects aged ≥18 years
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements to be conducted within 14 days prior to the first dose of study drug:
At least one measurable lesion based on RECIST 1.1
Availability of tumor tissue for molecular analysis is not mandatory (presence of archival tissue or re-biopsy for acquisition of tumor tissue is strongly recommended)
Exclusion Criteria:
Subjects are to be excluded from the study if they display any of the following criteria:
Prior radiotherapy (local palliative radiotherapy is permitted but must have occurred ≥2 weeks and subject must have no Grade 3 or 4 toxicities prior to first dose of study treatment; palliative is defined as not intended to cure but to relieve symptoms and reduce suffering)
Eligibility for local therapy (surgery or radiotherapy)
Previous treatment with any CDK inhibitors or docetaxel
Current or ongoing administration of anticoagulation or antiplatelet therapy. However, use of low-dose aspirin (≤100 mg/day) and/or low-dose heparin is permitted unless it is being used for conditions other than cancer
Known hypersensitivity to any of the study treatments or excipients of the preparations or any agent given in association with this study
Previous deep vein thrombosis (within the last 6 months), arterial thrombotic events (including strokes), or pulmonary embolism
History of cardiac disease: Congestive heart failure New York Heart Association (NYHA) Class III or IV angina (within past 6 months prior to study entry), myocardial infarction, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
Active clinically serious infections of NCI-CTCAE v4.0 >Grade 2
Known human immunodeficiency virus infection, active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
Seizure disorder requiring therapy (such as steroids or anti-epileptics)
Symptomatic metastatic brain or meningeal tumors, including those of the spinal cord, and including cases of neoplastic meningitis (also known as symptomatic carcinomatous meningitis or leptomeningeal carcinomatosis). However, after WBRT or GKS for symptomatic brain or leptomeningeal metastases, if subjects are stable for 2 weeks without steroid and the dosage of anti-convulsant is stable for 2 weeks, they are eligible. Asymptomatic central nervous system metastases are eligible if the subject has no abnormal findings on neurologic examination and is not receiving corticosteroid therapy to control symptoms.
History of organ allograft
Evidence or history of bleeding disorder, ie any hemorrhage / bleeding event of NCI-CTCAE v4.0 >Grade 2 within 4 weeks prior to the first dose of study treatment
Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg despite optimal medical management)
Serious, non-healing wound, ulcer, or bone fracture (bone fractures due to bone metastases are acceptable)
12. IPD Sharing Statement
Learn more about this trial
An Open-label Phase Ib/II Study of BAY 1000394 (Roniciclib) in Combination With Docetaxel in Second- or Third-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC)
We'll reach out to this number within 24 hrs