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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two drugs, topotecan and VX-970 (M6620, an ATR kinase inhibitor), can enhance treatment for small cell lung cancer. The researchers aim to determine if adding VX-970 improves chemotherapy by targeting cancer cells' repair mechanisms. Participants will receive close monitoring to ensure the treatment's safety and effectiveness. This trial may suit adults with small cell lung cancer who have undergone at least one round of chemotherapy. As a Phase 1 and Phase 2 trial, it focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take any strong inhibitors or inducers of CYP3A (a liver enzyme that processes drugs) during the study. It's best to discuss your current medications with the study team to see if they are allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of VX-970 (M6620) and topotecan is generally well-tolerated by patients. One study found that patients can safely receive the highest dose of these two drugs. This combination appears particularly effective for individuals with small-cell lung cancer who have not responded to platinum-based treatments. While side effects may occur, they are usually manageable. The study aimed to ensure that no more than 1 in 6 participants experienced a severe side effect, indicating that the treatment is relatively safe for most participants based on the available data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Topotecan and VX-970 (M6620) for small cell lung cancer (SCLC) because it offers a novel approach to treating this aggressive cancer. Unlike standard chemotherapy options such as cisplatin and etoposide, this treatment targets the ATR kinase pathway, which is involved in DNA repair. By inhibiting ATR kinase, VX-970 makes cancer cells more vulnerable to DNA damage, especially when combined with Topotecan, a drug that interferes with DNA replication. This dual approach could potentially enhance the effectiveness of treatment and overcome resistance seen with current therapies.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

This trial will evaluate the combination of VX-970 (also known as M6620) with topotecan for treating small cell lung cancer. Studies have shown that this combination can be effective, especially when the cancer doesn't respond to standard treatments. Research indicates that combining VX-970 with topotecan works better than using topotecan alone because VX-970 prevents cancer cells from repairing themselves, enhancing the chemotherapy's effectiveness. For patients whose cancer did not respond well to platinum-based chemotherapy, this combination appears particularly promising. Initial findings suggest that this treatment may lead to better tumor shrinkage compared to using topotecan alone, offering hope for improved outcomes in treating this challenging cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03896503

NCT03896503 | Randomized Trial of Topotecan With ... This phase II trial studies how well berzosertib (M6620) works when given in combination with topotecan hydrochloride (topotecan) compared with topotecan ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT03896503

Randomized Trial of Topotecan with M6620, an ATR ... This phase II trial studies how well berzosertib (M6620) works when given in combination with topotecan hydrochloride (topotecan) compared with topotecan alone.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29252124/

Phase I Study of ATR Inhibitor M6620 in Combination With ... The combination seems particularly active in platinum-refractory small-cell lung cancer, which tends not to respond to topotecan alone.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02487095

NCT02487095 | Trial of Topotecan With VX-970 (M6620), ... 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.

5. withpower.com withpower.com/trial/m6620-topotecan-for-small-cell-lung-cancer-f781a

M6620 + Topotecan for Small Cell Lung Cancer This trial is testing if combining two drugs, berzosertib and topotecan, works better than using topotecan alone for patients with relapsed small cell lung ...

6. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/nct03896503

Randomized Phase II Trial of Topotecan plus M6620 VX- ... Randomized Phase II Trial of Topotecan plus M6620 VX-970 vs. Topotecan alone in Patients with Relapsed Small-Cell Lung Cancer. Brief Summary ...