Clinical trial NCT03227016: Study in Patients With SCLC of Veliparib in Combination With Topotecan
Official title: Phase I/II Study in Patients With Small Cell Lung Cancer (SCLC) of Veliparib in Combination With Topotecan
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Small Cell Lung Cancer SCLC
Lead sponsor: Central European Society for Anticancer Drug Research
Sponsor class: OTHER
First posted: 2017-07-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: adverse events
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: München Gauting
country: Germany
facility: Klinik München Gauting
Study officials:
affiliation: Askelios Klinik München Gauting
name: Joachim von Pawel, MD
role: STUDY_CHAIR
References: