A Phase 1 Dose Escalation and Phase 2 Randomized Double-Blind Study of Veliparib in Combination with Carboplatin and Etoposide as a Therapy of Treatment-Naïve Extensive Stage Disease Small Cell Lung Cancer.
- Conditions
- extensive stage disease lung cancersmall cell lung cancer10038666
- Registration Number
- NL-OMON44322
- Lead Sponsor
- AbbVie B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 19
1. Subject with histologically or cytologically confirmed extensive stage SCLC which is newly diagnosed and chemotherapy naïve.;2. Phase 1 ONLY: histologically or cytologically confirmed advanced/metastatic solid tumors for which carboplatin/etoposide treatment is considered appropriate.;3. Subject in Phase 2 only: must have measureable disease per RECIST 1.1.;4. Subjects with ED SCLC must consent to provide available archived formalin fixed paraffin embedded (FFPE) tissue sample of SCLC lesion (primary or metastatic) for central review and biomarker analysis.;5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.;6. Subject must be >= 18 years of age.;7. Subject must have adequate hematologic, renal and hepatic function as follows:
• Bone Marrow: Absolute neutrophil count ANC >= 1,500/mm3 (1.5 × 10e9/L); White blood cells >= 3,000/mm3 (3 × 10e9/L); Platelets >= 100,000/mm3 (100 × 10e9/L); Hemoglobin >= 9 g/dL (5.58 mmol/L)
• Renal function: creatinine <= ULN or if creatinine > ULN calculated creatinine clearance via the Cockroft Gault formula of >= 50 mL/min
• Hepatic function:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 × upper limits of normal (ULN). For subjects with liver metastases, AST and ALT <= 5 × ULN;
- Bilirubin: <= 1.5 × ULN; for subjects with Gilbert's syndrome bilirubin > 1.5 × ULN is allowed if no symptoms of compromised liver function are present.;8. Subject must be able to swallow pills.;9. Female and male patients of fertile age, and/or their partners should use contraception. If male, subject and subject's female partner(s) of childbearing potential should practice at least one of the following methods of birth control. If female, subject must be either postmenopausal for at least 1 year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or the subject and the subject's male partner(s) practicing at least one of the following methods of birth control:
• total abstinence from sexual intercourse (if it is the subject's preferred and usual lifestyle; for minimum one complete menstrual cycle prior to study drug administration and to extend 6 months after treatment);
• vasectomized subject or partner(s);
• hormonal contraceptives (oral, parenteral or transdermal) for at least 90 days prior to study drug administration for the subject or subject's female partner(s);
• intrauterine device (IUD) for the subject or subject's female partner(s); or
• double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with (spermicidal jellies or creams) for the subject or subject's female partner(s). ;If hormonal contraceptives are used, the specific contraceptive must have been used for at least 90 days prior to study drug administration. If the subject or subject's female partner(s) is currently using a hormonal contraceptive, she should also use a barrier method during this study and for 6 months (or per local label) after study completion. ;Female subjects must have negative results for pregnancy tests performed:
• at Screening on a serum specimen obtained within 7 days prior to initial study drug administration, and
• prior to dosing on a urine sample obtained C1D-2 unless the serum pregnancy test was collected within 7 days of C1D-2. ;10. Must voluntarily sign and date each informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Rev
1. Phase 1 ONLY: Subject has had any prior anti-cancer therapy other than:
* Hormonal, non-myelosuppressive, biologic, targeted, or immune therapy (must be completed >= 4 weeks prior to Cycle 1 Day -2).
* One line of cytotoxic chemotherapy (must be completed >= 4 weeks prior to Cycle 1 Day -2).
* Adjuvant/neoaduvant radiotherapy (must be completed >= 12 months prior to Cycle 1 Day -2, with field not involving > 10% of bone marrow reserve).;2. Phase 2 ONLY: Subject has had any prior chemotherapy, radiotherapy, investigational anti-cancer agents or biologic therapy for the disease under study. Single non-target lesion irradiation with intent of symptom palliation is allowed if >= 2 weeks prior Cycle 1 Day -2.;3. Subject has known hypersensitivity to etoposide, platinum compounds or veliparib.;4. Phase 1 ONLY: Subject has received prior myelopoietic growth factors.;5. Subject has current central nervous system (CNS) or leptomeningeal metastases or history of CNS or leptomeningeal metastases. If CNS progression is suspected, a head CT should be performed at screening.;6. Subject has a history of seizures within 12 months of Cycle 1 Day -2 or diagnosed neurological
condition placing subject at the increased risk of seizures.;7. Subject has received traditional herbal anti-cancer medicine (e.g. Chinese, Asian, etc) within 14 days prior to Cycle 1 Day -2.;8. Subject has had major surgery within 6 weeks prior to Cycle 1 Day -2 (subjects must have
completely recovered from any previous surgery prior to Cycle 1 Day -2).;9. Subject has clinically significant and uncontrolled major medical condition(s) including but not
limited to:
* Uncontrolled nausea/vomiting/diarrhea;
* Active uncontrolled infection;
* History of hepatitis B (HBV) with surface antigen (HBsAg) positivity within 3 months prior to
the date of informed consent for this study (if no test has been performed within 3 months, it
must be done at screening);
* History of hepatitis C (HCV) with HCV RNA positivity within 3 months prior to the date of
informed consent for this study (if no test has been performed within 3 months it must be done
at screening);
* Symptomatic congestive heart failure (New York Heart Association [NYHA] class >= II);
* Unstable angina pectoris or cardiac arrhythmia;
* Psychiatric illness/social situation that would limit compliance with study requirements;
* Any other medical condition, which in the opinion of the Investigator, places the subject at an
unacceptably high risk for toxicities.;10. Subject is pregnant or lactating.;11. The subject has a history of another active cancer within the past 3 years except cervical cancer in situ, in situ carcinoma of the bladder, squamous or basal cell carcinoma of the skin or another in situ cancer that is considered cured by the investigator (e.g., in situ prostate cancer, breast ductal carcinoma in situ [DCIS]).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Objective Response Rate<br /><br>The proportion of subjects with objective response (CR or PR) as assessed by<br /><br>the investigator<br /><br><br /><br>Progression-Free Survival<br /><br>Progression-Free Survival will be defined as the number of days from the date<br /><br>of randomization to the date of earliest disease progression or death.<br /><br><br /><br>Overall Survival<br /><br>Overall survival will be defined as the number of days from the date of<br /><br>randomization to the date of death.<br /><br><br /><br>Duration of Overall Response<br /><br>Duration of overall response will be defined as the number of days from the<br /><br>date of first response (CR or PR) to the earliest documentation of progressive<br /><br>disease.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Not applicable.</p><br>