Topotecan + ATR Kinase Inhibitor for Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Symptomatic brain metastases, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 21 days per cycle

62 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with small cell lung cancer or related cancers, who've had chemotherapy. They must have a performance status indicating they can care for themselves and do light work, measurable disease by certain criteria, and agree to use contraception. Not eligible if they've had recent chemo, surgery, radiotherapy, or are pregnant.

Inclusion Criteria

Ability of subject to understand and the willingness to sign a written informed consent document.

I can take care of myself and am up and about more than half of the day.

I haven't had chemotherapy, major surgery in the last 4 weeks, or radiotherapy in the last 24 hours.

Exclusion Criteria

My tumor can potentially be cured with treatment.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to (study agent) or other agents used in study.

I do not have severe brain metastases or conditions that could affect my study participation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive topotecan IV on days 1-5 and VX-970 IV on day 5 alone or on days 2 and 5 in 21-day cycles

21 days per cycle

Weekly visits during the first cycle, every 3 weeks thereafter

Dose Escalation

Doses of topotecan and VX-970 are increased to determine the maximum safe dose

Until maximum tolerated dose is identified

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months

Follow-up phone calls

Treatment Details

Interventions

• Topotecan
• VX-970 (M6620)

Trial Overview The trial is testing the combination of topotecan (a chemotherapy drug) with VX-970 (M6620), which may inhibit cancer cells' DNA repair mechanisms. The study has two parts: finding the safest dose combination and then giving that dose to more participants to assess its effectiveness.

Participant Groups

Group I: 2/Phase II VX-970 (M6620) + topotecan Experimental Treatment 2 Interventions

VX-970 (M6620) + topotecan at maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D)

Group II: 1/Phase I VX-970 (M6620) + topotecan Experimental Treatment 2 Interventions

VX-970 (M6620) + topotecan at escalating doses

Topotecan is already approved in European Union, United States for the following indications:

Approved in European Union as Hycamtin for:

• Ovarian cancer
• Small cell lung cancer
• Cervical cancer

Approved in United States as Hycamtin for:

• Ovarian cancer
• Small cell lung cancer
• Cervical cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+