Study in Patients With SCLC of Veliparib in Combination With Topotecan

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

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

Study Overview

• Status: Unknown
• Conditions: Small Cell Lung Cancer SCLC
• Intervention / Treatment: Drug: veliparib; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • München Gauting, Germany
    • Recruiting
    • Klinik München Gauting
    • Contact: Joachim von Pawel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Central European Society for Anticancer Drug Research
• Investigators: Study Chair: Joachim von Pawel, MD, Askelios Klinik München Gauting

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: August 1, 2016
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Veliparib; Topotecan; Poly(ADP-ribose) Polymerase Inhibitors
• Other Study ID Numbers: C-II-011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No