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Study in Patients With SCLC of Veliparib in Combination With Topotecan

Phase 1
Conditions
Small Cell Lung Cancer SCLC
Interventions
Registration Number
NCT03227016
Lead Sponsor
Central European Society for Anticancer Drug Research
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Combination Topo/VeliveliparibTopotecan and Veliparib in increasing doses
Combination Topo/VeliTopotecanTopotecan and Veliparib in increasing doses
Primary Outcome Measures
NameTimeMethod
adverse events6 months

adverse events related to study drug(s) qualifying as Dose-Limiting Toxicities (DLT)

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Klinik München Gauting

🇩🇪

München Gauting, Germany

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