Topotecan Plus M6620 (VX-970) vs. Topotecan Alone in People With Relapsed Small-Cell Lung Cancer

Solid Tumors Clinical Trial

Official title: Randomized Phase II Trial of Topotecan Plus M6620 (VX-970) vs. Topotecan Alone in Patients With Relapsed Small-Cell Lung Cancer

Status Recruiting

Clinical Trial Summary

Background:

Small cell cancers are aggressive and grow fast. They can appear in the lungs and in other parts of the body. These tumors often don t respond well to treatment if they come back after chemotherapy. Treatment with two drugs combined may be able to help.

Objective:

To compare M6620 plus topotecan to topotecan alone in people with small cell lung cancer (SCLC). Also, to test the effects of M6620 plus topotecan in people with small cell cancer outside the lungs.

Eligibility:

People ages 18 and older with relapsed SCLC or small cell cancer outside the lungs

Design:

Participants will be screened with:

Physical exam

Blood and heart tests

CT scan

Tumor biopsy: This is mandatory for participants with SCLC. It is optional for those with small cell cancer outside the lungs.

Participants with SCLC will be randomly assigned to 1 of 2 groups: to receive either M6620 and topotecan or topotecan alone. Outside of the lungs small cell cancer participants will be assigned to receive both drugs.

Participants will receive treatment in 21-day cycles. They will get topotecan through a vein in the arm on days 1 5 of each cycle. Some participants also will receive M6620 through a vein in the arm on days 2 and 5 of each cycle.

Participants will have blood tests and physical exams every cycle. They will have CT scans every 6 weeks.

Participants will continue treatment as long as their cancer does not get worse and they can handle the side effects.

After treatment, participants will have visits every 3 months. Visits will include blood tests and CT scans.

Patients randomized 2:1 ie 2 times more likely to get the combination vs. single drug

Patients who receive single drug may receive the combination at the time of progression

Clinical Trial Description

Background:

• SCLC is the most aggressive and lethal form of lung cancer. It represents 15% of all lung cancers, with an annual incidence of over 34,000 cases in the United States alone.

• Relapsed SCLC has been traditionally classified into sensitive and resistant disease according to the type of response to first-line therapy and to treatment-free interval.

• Topotecan is Food and Drug Administration (FDA)-approved for patients with SCLC with chemotherapy-sensitive disease after failure of first-line chemotherapy (platinum and etoposide).

• Topotecan inhibits re-ligation of topoisomerase I-mediated single-strand DNA breaks leading to lethal double-strand DNA breaks (DSB).

• We showed that inhibition of ATR by short interfering RNA or VE-821 and its clinical derivative M6620 sensitizes tumor cells to TOP1 inhibitors.

• We found that a combination of an Ataxia telangiectasia and Rad3-related (ATR) inhibitor and topotecan can be safely combined and that heightening replicative stress in this manner can yield durable responses in small cell cancers and initiated a Phase 1/2 trial of the

combination.

• In this current study, we hypothesize that the combination of M6620 and topotecan can improve progression free survival (PFS) compared with topotecan alone in patients with relapsed SCLC.

• In the recently reported phase I clinical trial, we defined a safe and effective dose of topotecan plus M6820. The proposed randomized phase II trial is based on promising preliminary efficacy data seen in SCLC patients treated on phase I and the ongoing phase II trials.

Objectives:

-To determine if the combination of M6620 with topotecan will result in an improvement in progression-free survival (PFS) compared to topotecan alone in patients with relapsed small cell lung cancer (SCLC).

Eligibility:

-Patients enrolled to the primary cohort must have limited- or extensive-disease SCLC at diagnosis, with extensive disease at study entry with measurable disease at random assignment per RECIST 1.1. Both platinum-sensitive and platinum-resistant patients will

be included.

• Patients must be greater than or equal to18 years of age

• Patients who have received prior topotecan therapy are not eligible.

• Patients who are receiving any other investigational agents, and with uncontrolled intercurrent illness are not eligible.

Design:

• This study is an open label, randomized phase 2 study of patients with relapsed SCLC.

• SCLC patients who have failed prior therapy will be randomized 2:1 to receive either topotecan in combination with M6620 or topotecan alone.

• Patients will be stratified at the time of randomization for being sensitive or resistant/refractory to prior therapy.

• Patients on the topotecan monotherapy arm will be eligible to cross-over to receive the combination treatment at progression.

• It is expected that approximately 25-30 patients per year (about 2-3 patients per month) can be accrued onto the randomized portion of this trial, and thus accrual will be completed in approximately 2 years.

• A separate cohort of 20 patients with extrapulmonary small cell cancer will be accrued while the primary cohort is accruing and will only receive the combination therapy.

• This is planned as a multicenter study through CTEP. NCI CCR will be the lead and coordinating site ;

Related Conditions & MeSH terms

• Carcinoma, Small Cell
• Extrapulmonary Lung Cancer
• Lung Neoplasms
• Relapse
• SCLC
• Small Cell Lung Carcinoma
• Solid Tumors

• NCT number: NCT04162041
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Rasa Vilimas, R.N.
• Phone: (240) 858-3158
• Email: rasa.vilimas@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: November 20, 2019
• Completion date: December 1, 2022