NCT02487095CompletedPhase 1/2
Trial of Topotecan With VX-970 (M6620), an ATR Kinase Inhibitor, in Small Cell Cancers and Extrapulmonary Small Cell Cancers
A Phase I/II Trial of Topotecan With VX-970 (M6620), an ATR Kinase Inhibitor in Small Cell Cancers
Source: ClinicalTrials.gov · Last updated 13 Apr 2025
Brief summary (registry, in English)
Background: Chemotherapy damages cancer cell deoxyribonucleic acid (DNA) so the cells die, and the tumor shrinks. But it may stop working in some people over time. This is partly due to efficient DNA damage repair mechanisms used by tumor cells. VX-970 (M6620) may stop cancer cells from preventing the repair of DNA damaged by chemotherapy. The purpose of this study is to see if using the chemotherapy drug topotecan along with the drug VX-970 (M6620) will improve the response to chemotherapy. Objective: To study the safety and efficacy of VX-970 (M6620) and topotecan in treating small cell lung cancer. Eligibility: Adults at least 18 years old with small cell lung cancer. Design: Participants will be screened with medical history, physical exam, blood and heart tests, and scans. Most of these tests are part of their routine care. Most of these tests will be repeated throughout the study. The study is set in 21-day cycles. Participants will get topotecan intravenous (IV) on days 1 through 5. They will get VX-970 (M6620) IV on day 5 alone or on day 5 and day 2. Participants doctors will monitor them weekly for the first cycle, every 3 weeks after that. For Part 1 of this Study the doses of topotecan and VX-970 (M6620) will be increased (according to the Protocol) to determine the maximum safe dose of the combination. The maximum safe dose of the combination is the dose at which no more than 1 in 6 people have an intolerable side effect. More participants will join in Phase 2. They will take the drugs at the maximum safe dose, on the same schedule as the drugs were taken in Phase 1. Participants will give samples of blood, hair, and tumor tissue (optional) at different times. They will discuss side effects at every visit. A month after stopping taking the drugs, participants will have a physical exam and blood drawn. They will have follow-up phone calls every 3 months.
- Status (registry)
- Completed
- Phase (registry)
- Phase 1/2
- Study type
- Interventional
- Enrollment
- 62 (actual)
- First submitted
- 27 Jun 2015
- Start date
- 30 Jul 2015
- Primary completion date
- 24 Feb 2021
- Lead sponsor
- National Cancer Institute (NCI)
- NCT number
- NCT02487095
What you commit to
- Study type: Interventional · Phase 1/2
- Participants enrolled: 62
- From 30 Jul 2015 to the primary completion date, 24 Feb 2021
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Subjects with tumor amenable to potentially curative therapy.
- Subjects who are receiving any other investigational agents.
- Subjects requiring any medications or substances that are strong inhibitors or inducers of cytochrome p450, family 3, subfamily A (CYP3A) during the course of the study are ineligible. Lists including strong inhibitors and inducers of cytochrome p450 3A4 (CYP3A4) are provided.
- Subjects with evidence of severe or uncontrolled systemic disease, or any concurrent condition, which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, stroke/cerebrovascular accident within the past 6 months, or psychiatric illness/social situations which would jeopardize compliance with the protocol.
- Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with VX-970 (M6620). In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy.
- Pregnant women are excluded from this study because topotecan is a Class D agent with the potential for teratogenic or abortifacient effects and because the effects of VX-970 (M6620) on the developing human fetus are currently unknown. In addition, because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with topotecan or VX-970 (M6620), breastfeeding should be discontinued if the mother is treated with these agents.
Other illness
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to (study agent) or other agents used in study.
- Subjects with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, subjects who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for 1 week or on physiologic doses of steroids may be enrolled.
Criteria the registry did not label
- INCLUSION CRITERIA:
- Both Phase I and Phase II:
- Male and female subjects greater than or equal to 18 years of age. Because no dosing adverse event data are currently available on the use of topotecan in combination with VX-970 (M6620) in subjects less than 18 years of age, children are excluded from this study, but will be eligible for future pediatrics trials.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
- Patients must have measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Subjects with evaluable, but not measurable disease will be eligible for Phase 1.
- Subjects must not have received chemotherapy or undergone major surgery within 4 weeks and radiotherapy within 24 hours prior to enrollment.
- Adequate organ functions
- Hemoglobin greater than or equal to 9.0 g/dL
- Absolute neutrophil count greater than or equal to 1.5x10\^9/L
- Platelets greater than or equal to 100x10\^9/L
- Total Bilirubin less than or equal to 2.0 mg/dL
- Transaminases less than or equal to 2 x upper limit of normal (ULN) or if liver metastases were present, less than or equal to 3xULN
- Creatinine less than or equal to 1.5 mg/dL or creatinine clearance by Cockcroft-Gault formula greater than or equal to 60 mL/min
- Ability of subject to understand and the willingness to sign a written informed consent document.
- The effects of VX-970 (M6620) on the developing human fetus are unknown For this reason and because topotecan is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during study participation and for 6 months after the last dose study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Phase I:
- Subjects with histologically confirmed small-cell lung cancer (SCLC), non- small cell lung cancer (NSCLC), ovarian cancer, cervical cancer, and neuroendocrine cancers will be eligible. Pathological confirmation of diagnosis will be done at National Cancer Institute (NCI) Laboratory of Pathology. Patients with other histologies will be allowed if no standard treatment options exist.
- At least one prior chemotherapy
- NSCLC subjects with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) translocations should have previously received appropriate Food and Drug Administration (FDA) approved therapies in addition to prior chemotherapy
- Phase II:
- Histological confirmation of SCLC, or extrapulmonary small cell cancer. Although NCI confirmation of pathology is not required prior to starting treatment, every effort will be made to obtain outside pathology to be reviewed by an NCI pathologist.
- Subjects with both platinum-sensitive and platinum-refractory disease will be eligible
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike Coordinator of this site? Confirm its status | Bethesda | United States | Unknown status |
Related publications
- Plasma nucleosome profiling reports on tumor burden and molecular subtypes in small cell lung cancer.J Clin Invest · 2026 · PMID 42820295
This page is information, not medical advice. Discuss any trial with your doctor.