Study in Patients With SCLC of Veliparib in Combination With Topotecan

Study Overview
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Brief Summary
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Phase I/II Study in Patients With Small Cell Lung Cancer (SCLC) of Veliparib in Combination With Topotecan

Detailed Description
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For this study sensitive or refractory SCLC patients (refractory to prior chemotherapy defined as having experienced no response or a relapse within 90 days after the end of chemotherapy) will be eligible. In total, around 130 patients will be enrolled, around 30 evaluable patients in phase I and 100 patients in phase II. The study will consist of two parts: A preceding Phase I part will be performed to identify the Recommended Dose of veliparib to be administered in the Phase II part in combination with topotecan at the dose regimen of 1.25 mg/m2 (on days 1-5 of a 3 week cycle [d1-5q21d]). Each patient will be subjected to an initial cycle of topotecan monotherapy (1.25 mg/m2 on day 1-5 of a 3 week cycle); this run-in cycle shall prove topotecan tolerance of the candidates. Only patients who do not reveal any DLTs receive further treatment with combination therapy. In a dose-escalating 3+3 design the RD of veliparib for the subsequent Phase II part of the study will be defined during a maximum of 5 cycles combination therapy. The Phase II part will follow upon completion of Phase I.

Official Title
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Phase I/II Study in Patients With Small Cell Lung Cancer (SCLC) of Veliparib in Combination With Topotecan

Conditions
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Small Cell Lung Cancer SCLC

Intervention / Treatment
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* Drug: veliparib
* Drug: Topotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥ 18 years of age Subject with progressive or recurrent ED-SCLC after first line platinum-based therapy, which is either histologically or cytologically confirmed Performance status (PS) 0-2 ECOG Adequate bone marrow reserve Total bilirubin < 2 x upper limit of normal AST and ALT < 2.5 x upper limit of normal, or < 5 x upper limit of normal in case of liver metastases Serum creatinine < 2 x upper limit of normal or creatinine clearance > 50 ml/min Exclusion Criteria: Other anti-cancer chemotherapy or radiotherapy Symptomatic motor or sensory neuro-toxicities CTCAE > Grade 2 or any other unresolved toxicities from prior systemic anti-cancer therapy or radiotherapy CTCAE > Grade 1 Known hypersensitivity to topotecan or veliparib Brain or meningeal metastasis (unless they are asymptomatic and not requiring systemic corticosteroid therapy) Major surgery within 6 weeks prior to first treatment on study (subjects must have completely recovered from any previous surgery prior to first treatment on study). History of cardiac events within the past 3 months Uncontrolled severe hypertension Abdominal or tracheo-oesophageal fistula, gastrointestinal perforation, or intra-abdominal abscess Uncontrolled nausea / vomiting / diarrhea Previous malignancy (other than SCLC) in the last 3 years, except basal cell cancer of the skin, pre-invasive cancer of the cervix, T1a prostate carcinoma or superficial bladder tumor [Ta, Tis and T1] that was cured in the opinion of the investigator. History of organ allograft Active (acute or chronic) or uncontrolled infection of bacterial, mycotic or viral genesis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Topo/Veli<br>Topotecan and Veliparib in increasing doses | Drug: veliparib<br>* Topotecan at increasing doses (1x or 2x per day) will be administered in each cycle.<br>* Other names: PARP inhibitor;Drug: Topotecan<br>* Topotecan at dose 1.25 mg/m2 will be administered in each cycle.<br>* Other names: Hycamtin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | adverse events related to study drug(s) qualifying as Dose-Limiting Toxicities (DLT) | 6 months |