Study in Patients With SCLC of Veliparib in Combination With Topotecan

Central European Society for Anticancer Drug Research

Status and phase

Unknown

Phase 1

Conditions

Small Cell Lung Cancer SCLC

Treatments

Drug: veliparib

Drug: Topotecan

Study type

Interventional

Funder types

Other

Identifiers

NCT03227016

C-II-011

Details and patient eligibility

About

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

Full 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.

Enrollment

30 estimated patients

Sex

All

Ages

18 to 85 years old

Volunteers

No Healthy Volunteers

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