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BAY 1512
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12-1139
Phase Ib / II study of BAY 1000394 in combination with cisplatin / etoposide or carboplatin/etoposide as first-line therapy in subjects with extensive disease small cell lung cancer
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Drug(s)
| BAY 1000394 |
| Carboplatin |
| Cisplatin |
| Etoposide |
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Description
- Phase Ib part of the study
- Primary: Determine the safety, tolerability, pharmacokinetics, and maximum tolerated dose of BAY 1000394 in combination with cisplatin / etoposide or carboplatin / etoposide chemotherapy in 2 separate cohorts in parallel
- Secondary: Assess the biomarker response profile of BAY 1000394, overall survival, progression-free survival, response rate, duration of response, stable disease and disease control rate
- Phase II part of the study
- Primary: Evaluate the response rate in subjects with extensive disease SCLC receiving first-line cisplatin / etoposide or carboplatin / etoposide chemotherapy in combination with BAY 1000394. Tumor response will be evaluated based on RECIST 1.1. Tumor measurements will be made at baseline and then every 2 cycles, ie every 6 weeks based on 21-day cycles, until progressive disease will occur
- Secondary: Determine the tolerability, safety profile, biomarker response profile, overall survival, progression-free survival, duration of response, and stable disease and disease control rate for the combination of BAY 1000394 and chemotherapy and subsequent maintenance with BAY 1000394
Inclusion Criteria
- Male or female subjects aged ≥ 18 years.
- Histologically or cytologically confirmed, extensive disease SCLC
- At least 1 solid tumor lesion measurable by computer tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1 (see Section 14.7). Subjects with non-measurable disease according to RECIST 1.1 can be included in the Phase Ib part of the study
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 (see Section 14.6)
- Life expectancy of at least 12 weeks
- Serum sodium ≥ 130 mmol/L
- 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:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥ 2 x 10^9/L
- Platelet count ≥ 100 x 10^9/L
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
- ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
- INR and PTT ≤ 1.5 x ULN. Subjects on warfarin can only be enrolled if their clinical situation allows a switch to low-molecular-weight heparin and if they fulfill the aforementioned INR and PTT criteria
- Estimated glomerular filtration rate ≥ 60 mL/min per 1.73 m^2 according to the Modification of Diet in Renal Disease Study Group (MDRD) formula (see Section 14.8)
- Negative serum pregnancy test must be obtained within 7 days prior to the start of treatment in women of childbearing potential. Negative results must be available prior to study drug administration
- Agreement by women of childbearing potential as well as men to use adequate contraception prior to study entry and for the duration of study participation including the 30-day period after the last dose of study drug. These procedures should be documented in source documents. The investigator should advise the subject how to achieve adequate contraception. Postmenopausal women are defined as:
- Age > 50 years with amenorrhea for at least 12 months or
- Age ≤ 50 years with 6 months of spontaneous amenorrhea and follicle stimulating hormone (FSH) level within postmenopausal range (>40 mIU/mL) or
- Bilateral oophorectomy
- Men and women enrolled in this study must use adequate barrier birth control measures prior to and during the course of the study. An adequate contraception includes a hormonal contraception with implants or combined oral contraceptives, certain intrauterine devices, bilateral tubal ligation, hysterectomy, or vasectomy of the partner. In addition, the use of condoms for subjects or their partners is required
- Subjects with a history of hypertension should be on a stable anti-hypertensive treatment for more than 7 days prior to the first dose of study drug
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study-specific procedures
Exclusion Criteria
Medical and surgical history- Prior systemic anticancer therapy
- Prior radiotherapy (local palliative radiotherapy is permitted)
- Known hypersensitivity to any of the study drugs or excipients of the preparations or any agent given in association with this study
- History of cardiac disease: congestive heart failure > NYHA Class II, unstable angina (anginal symptoms at rest), any episodes of angina or history of myocardial infarction, cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted), previous venous or arterial thrombotic events, pulmonary embolism)
- Moderate or severe hepatic impairment, ie Child-Pugh class B or C
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
- Active clinically serious infections of CTCAE > Grade 2 (Section 14.5)
- Symptomatic metastatic brain or meningeal tumors. Subjects with asymptomatic brain metastases must not be on acute steroid therapy or taper off steroid therapy (chronic steroid therapy is acceptable provided that the dose is stable for 4 weeks prior to study entry and following screening CT / MRI scan). Subjects with neurological symptoms should undergo a CT / MRI scan of the brain to exclude new or progressive brain metastases. Spinal cord metastasis is acceptable
- Seizure disorder requiring therapy (such as steroids or anti-epileptics)
- History of organ allograft
- Evidence or history of bleeding disorder, ie any hemorrhage / bleeding event of CTCAE > Grade 2 (Section 14.5) within 4 weeks prior to the first dose of study drug
- 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
- Subjects on dialysis
- Sensory neuropathy with sensory alterations or paresthesia (including tingling), interfering with function (≥ CTCAE Grade 2) (Section 14.5)
- Previous or coexisting cancer that is distinct in primary site or histology from the cancer evaluated in this study EXCEPT cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis], or any cancer curatively treated > 3 years prior to study entry
- Any condition that is unstable or could jeopardize the safety of the subject and his/her compliance in the study
- Subjects unable to swallow oral medications
- Any malabsorption condition
- Unresolved specific chronic toxicity CTCAE > Grade 2 (excluding cases of alopecia) (Section 14.5)
Medication, drug use, and special behavioral patterns- Major surgery, open biopsy, or significant trauma within 4 weeks prior to the first dose of study drug is excluded
- Autologous bone marrow transplant or stem cell rescue within 4 months prior to first dose of study drug is not allowed
- Investigational drug treatment outside of this study during or within 4 weeks prior to study entry. Toxic effects of previous investigational drug treatment have to be normalized
- Prior exposure to any of the study drugs
- Substance abuse, medical, psychological, or social conditions that may interfere with the subjects participation in the study or evaluation of the study results
Laboratory examination- Pregnant or breast-feeding women. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the first dose of study drug
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