Randomized Trial of Topotecan With M6620, an ATR Kinase Inhibitor, in Small Cell Lung Cancers and Small Cell Cancers Outside of the Lungs

Running, not enrolling · Phase 2

Conditions studied: 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

In brief

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.

Key facts

Study ID: NCT03896503
Run by: National Cancer Institute (NCI)
People needed: 104
Starts: 2019-12-30
Expected to finish: 2027-05-13
Last updated by the study team: 2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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, indinavir, nelfinavir and saquinavir) or inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) should be avoided. Patients requiring any medications or substances that are strong inhibitors or inducers of CYP3A during the course of the study are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or of which to minimize use. The Patient Drug Interactions Handout and Wallet Card should be provided to patients. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Patients with uncontrolled intercurrent illness
Pregnant women are excluded from this study because M6620 as a DDR inhibitor may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M6620, breastfeeding should be discontinued if the mother is treated with M6620. These potential risks may also apply to topotecan used in this study
Patients with high grade neuroendocrine cancers, but with no small cell morphology will not be eligible
Patients with psychiatric illness/social situations that would limit compliance with study requirements
Patients with Li-Fraumeni syndrome will not be eligible

Where it is running

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
University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States
University of Kansas Hospital-Indian Creek Campus — Overland Park, Kansas, United States
Mercy Hospital Pittsburg — Pittsburg, Kansas, United States
Salina Regional Health Center — Salina, Kansas, United States
University of Kansas Health System Saint Francis Campus — Topeka, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States
University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States
NCI - Center for Cancer Research — Bethesda, Maryland, United States
Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States
Weisberg Cancer Treatment Center — Farmington Hills, Michigan, United States
University Health Truman Medical Center — Kansas City, Missouri, United States
University of Kansas Cancer Center - North — Kansas City, Missouri, United States
University of Kansas Cancer Center - Lee's Summit — Lee's Summit, Missouri, United States
University of Kansas Cancer Center at North Kansas City Hospital — North Kansas City, Missouri, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center — Lebanon, New Hampshire, United States

Full record on ClinicalTrials.gov

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