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
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
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
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