Randomized Phase II Trial of Topotecan Plus M6620 (VX-970, Berzosertib) Vs. Topotecan Alone in Patients With Relapsed Small-Cell Lung Cancer

Study of Topotecan Plus M6620 in Small Cell Lung Cancer

NCT: NCT03896503 · Status: ACTIVE NOT RECRUITING · Phase: Phase 2 · Sponsor: National Cancer Institute (NCI) · Started: 2019-12-30 · Est. Completion: 2026-06-23

Plain English Summary

Randomized Trial of Topotecan With M6620, an ATR Kinase Inhibitor, in Small Cell Lung Cancers and Small Cell Cancers Outside of the Lungs is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Extensive Stage Lung Small Cell Carcinoma, Extrapulmonary Small Cell Neuroendocrine Carcinoma, Limited Stage Lung Small Cell Carcinoma, Platinum-Resistant Lung Small Cell Carcinoma, Platinum-Sensitive Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma. Tests a new drug, M6620, combined with topotecan to treat small cell lung cancer that has come back or started in other parts of the body. For patients with small cell lung cancer who have had previous treatment or whose cancer has returned. Participation involves IV treatments, blood tests, and scans. Patients will be randomly assigned to receive either the new drug or topotecan alone. Alternative treatments include standard chemotherapy and targeted therapies. The trial aims to enroll 104 participants.

Official Summary

This phase II trial studies how well berzosertib (M6620) works when given in combination with topotecan hydrochloride (topotecan) compared with topotecan alone in treating patients with small cell lung cancer that has come back (relapsed), or small cell cancer that arises from a site other than the lung (extrapulmonary). Drugs used in chemotherapy, such as topotecan hydrochloride, work by damaging the DNA (deoxyribonucleic acid) in tumor cells, causing those cells to die and the tumor to shrink. However, some tumor cells can become less affected by chemotherapy because they have ways to repair the damaged DNA. The addition of M6620 could help topotecan hydrochloride shrink the cancer and prevent it from returning by blocking enzymes needed for DNA repair.

Who Can Participate

Here is what you need to know about eligibility for this trial. Ages 18 and older, in good health with no major heart issues. No history of other cancers, and no current symptoms of heart disease. Must be on effective HIV treatment with undetectable viral load. Women of child-bearing potential must use contraception, and men must also use contraception. This trial is studying Extensive Stage Lung Small Cell Carcinoma, Extrapulmonary Small Cell Neuroendocrine Carcinoma, Limited Stage Lung Small Cell Carcinoma, Platinum-Resistant Lung Small Cell Carcinoma, Platinum-Sensitive Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures focus on how long patients can go without their cancer getting worse, which is crucial for improving survival rates. The specific primary outcome measures are: Progression-free Survival (PFS) Reported With 80% Confidence Interval (From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months after last participant has enrolled; up to 2 years for pulmonary cohort and up 31.5 months for Exploratory Cohort.); Progression-free Survival (PFS) Reported With 95% Confidence Interval (From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months after last participant has enrolled; up to 2 years for pulmonary cohort and up 31.5 months for Exploratory Cohort.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to fill a treatment gap for small cell lung cancer by testing a new drug that could potentially improve outcomes for patients. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Extensive Stage Lung Small Cell Carcinoma, Extrapulmonary Small Cell Neuroendocrine Carcinoma, Limited Stage Lung Small Cell Carcinoma, Platinum-Resistant Lung Small Cell Carcinoma, Platinum-Sensitive Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma, where improved treatment options are needed.

Investor Insight

The market for small cell lung cancer treatments is growing, with limited options available, making this trial significant for investors. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits and risks. Participation involves IV treatments, blood tests, and scans every few weeks. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

  • Study Type: INTERVENTIONAL
  • Allocation: RANDOMIZED
  • Model: PARALLEL
  • Masking: NONE
  • Enrollment: 104 participants

Interventions

  • DRUG: Berzosertib — Given IV
  • PROCEDURE: Biopsy Procedure — Undergo a tumor biopsy
  • PROCEDURE: Biospecimen Collection — Undergo blood sample collection
  • PROCEDURE: Computed Tomography — Undergo a CT scan
  • DRUG: Topotecan Hydrochloride — Given IV

Primary Outcomes

  • Progression-free Survival (PFS) Reported With 80% Confidence Interval (From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months after last participant has enrolled; up to 2 years for pulmonary cohort and up 31.5 months for Exploratory Cohort.)
  • Progression-free Survival (PFS) Reported With 95% Confidence Interval (From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months after last participant has enrolled; up to 2 years for pulmonary cohort and up 31.5 months for Exploratory Cohort.)

Secondary Outcomes

  • Objective Response Rate (ORR) (Up to 2 years)
  • Overall Survival (OS) Reported With 80% Confidence Interval (Up to 2 years for pulmonary cohort and up 31.5 for Exploratory Cohort.)
  • Overall Survival (OS) Reported With 95% Confidence Interval (Up to 2 years for pulmonary cohort and up 31.5 for Exploratory Cohort)

Full Eligibility Criteria

Inclusion Criteria:

* Patients enrolled to the primary cohort must have limited- or extensive-disease SCLC at diagnosis, with relapse at study entry with measurable disease at random assignment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Both platinum-sensitive and platinum-resistant patients will be included
* Patients with extrapulmonary small cell cancers (cancers with small cell morphology and arising outside the lung, such as small cell prostate, bladder, etc.) will be eligible for the exploratory cohort
* Patients must be \>= 18 years of age because no dosing or adverse event data are currently available on the use of M6620 in combination with topotecan in patients \<18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Hemoglobin \>= 9.0 g/dL - patients may receive transfusion to meet the hemoglobin (Hb) eligibility
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 2 mg/dL
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN)
* Creatinine =\< institutional ULN OR
* Glomerular filtration rate (GFR) \>= 60 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are eligible as long as they are on effective anti-retroviral therapy with undetectable viral load within 6 months and there is no drug-drug interaction with M6220
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* The effects of M6620 on the developing human fetus are unknown. For this reason and because DNA-damage response (DDR) inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completion of M6620 administration. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after completion of M6620 administration
* Patients with treated brain metastases are eligible if they are symptomatically stable while off steroid therapy for a minimum of 21 days
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Patients with symptomatic brain metastasis are not eligible due to their extremely poor prognosis and since it is unclear whether the investigational agent penetrates the blood-brain barrier. However, subjects who have had treatment for their brain metastasis and are symptomatically stable while off steroid therapy for a minimum of 21 days may be enrolled
* Patients who have received prior topotecan therapy
* Patients who have had chemotherapy or radiotherapy within 3 weeks prior to enrollment.

  * Note: Patients who have had palliative radiotherapy may be included as long as they have recovered from any radiotherapy related adverse events (allow at least a week between radiotherapy completion and study treatment)
* Patients who have not recovered from adverse events due to prior anti-cancer therapy except hair loss and peripheral neuropathy (i.e., have residual toxicities \> grade 1)
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 or topotecan used in study
* M6620 is primarily metabolized by cytochrome P450 3A4 (CYP3A4); therefore, concomitant administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinav

Trial Locations

  • Los Angeles General Medical Center, Los Angeles, California, United States
  • USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
  • USC Norris Oncology/Hematology-Newport Beach, Newport Beach, California, United States
  • University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
  • UCHealth University of Colorado Hospital, Aurora, Colorado, United States
  • University of Kansas Clinical Research Center, Fairway, Kansas, United States
  • HaysMed, Hays, Kansas, United States
  • University of Kansas Cancer Center, Kansas City, Kansas, United States
  • Lawrence Memorial Hospital, Lawrence, Kansas, United States
  • The University of Kansas Cancer Center - Olathe, Olathe, Kansas, United States
  • ...and 10 more locations

Frequently Asked Questions

What is clinical trial NCT03896503?

NCT03896503 is a Phase 2 INTERVENTIONAL study titled "Randomized Trial of Topotecan With M6620, an ATR Kinase Inhibitor, in Small Cell Lung Cancers and Small Cell Cancers Outside of the Lungs." It is currently active, not recruiting and is sponsored by National Cancer Institute (NCI). The trial targets enrollment of 104 participants.

What conditions does NCT03896503 study?

This trial investigates treatments for Extensive Stage Lung Small Cell Carcinoma, Extrapulmonary Small Cell Neuroendocrine Carcinoma, Limited Stage Lung Small Cell Carcinoma, Platinum-Resistant Lung Small Cell Carcinoma, Platinum-Sensitive Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma. The primary condition under study is Extensive Stage Lung Small Cell Carcinoma.

What treatments are being tested in NCT03896503?

The interventions being studied include: Berzosertib (DRUG), Biopsy Procedure (PROCEDURE), Biospecimen Collection (PROCEDURE), Computed Tomography (PROCEDURE), Topotecan Hydrochloride (DRUG). Given IV

What does Phase 2 mean for NCT03896503?

Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.

What is the current status of NCT03896503?

This trial is currently "Active, Not Recruiting." It started on 2019-12-30. The estimated completion date is 2026-06-23.

Who is sponsoring NCT03896503?

NCT03896503 is sponsored by National Cancer Institute (NCI). The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT03896503?

The trial aims to enroll 104 participants. The trial status is active, not recruiting.

How is NCT03896503 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs none masking.

What are the primary outcomes being measured in NCT03896503?

The primary outcome measures are: Progression-free Survival (PFS) Reported With 80% Confidence Interval (From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months after last participant has enrolled; up to 2 years for pulmonary cohort and up 31.5 months for Exploratory Cohort.); Progression-free Survival (PFS) Reported With 95% Confidence Interval (From start of treatment to time of progression or death, whichever occurs first, assessed at 6 months after last participant has enrolled; up to 2 years for pulmonary cohort and up 31.5 months for Exploratory Cohort.). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT03896503 being conducted?

This trial is being conducted at 20 sites, including Los Angeles, California; Newport Beach, California; Sacramento, California; Aurora, Colorado and 16 more sites (United States).

Where can I find official information about NCT03896503?

The official record for NCT03896503 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT03896503. This government database provides the most up-to-date and detailed information about the trial.

What is NCT03896503 testing in simple terms?

Tests a new drug, M6620, combined with topotecan to treat small cell lung cancer that has come back or started in other parts of the body. For patients with small cell lung cancer who have had previous treatment or whose cancer has returned.

Why is this trial significant?

This trial aims to fill a treatment gap for small cell lung cancer by testing a new drug that could potentially improve outcomes for patients.

What are the potential risks of participating in NCT03896503?

Potential side effects include nausea, fatigue, and hair loss. More serious risks may include liver issues and heart problems. Patients should be monitored closely for any adverse reactions. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT03896503?

Ask your doctor about your eligibility and the potential benefits and risks. Participation involves IV treatments, blood tests, and scans every few weeks. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT03896503 signal from an investment perspective?

The market for small cell lung cancer treatments is growing, with limited options available, making this trial significant for investors. This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.

What happens if the treatment in this trial doesn't work?

Participation involves IV treatments, blood tests, and scans. Patients will be randomly assigned to receive either the new drug or topotecan alone. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.