Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Carcinoma, Neuroendocrine

Adenocarcinoma

Prostatic Neoplasms

Carcinoma, Small Cell

Hypersensitivity

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Inflammatory Agents

Micronutrients

Vitamins

Androgens

Hormones

Abiraterone Acetate

Prednisone

Cortisone

Androgen Antagonists

Ascorbic Acid

Methyltestosterone

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Estrogens, Conjugated (USP)

Estrogens

Glucocorticoids

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Antioxidants

Protective Agents

Trace Elements

Anabolic Androgenic Steroids

Anabolic Agents

Vitamin C

Patients receive ADT per standard of care. Beginning 2 months after start of ADT, patients also receive abiraterone acetate and prednisone per standard of care for at least 6 months in the absence of disease progression or unacceptable toxicity.

Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10 weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease progression or unacceptable toxicity.

Antiandrogen Therapy

Undergo Abiraterone Acetate Treatment SOC

Radiation Therapy

Jing Zeng

This phase II trial studies how well antiandrogen therapy, abiraterone acetate, and prednisone with or without neutron radiation therapy work in treating patients with prostate cancer. Hormone therapy such as antiandrogen therapy may fight prostate cancer by blocking the production and interfering with the action of hormones. Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Neutron radiation therapy uses high energy neutrons to kill tumor cells and shrink tumors. It is not yet known whether antiandrogen therapy, abiraterone acetate, and prednisone with or without neutron radiation therapy may work better in treating patients with prostate cancer.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ADT per standard of care. Beginning 2 months after start of ADT, patients also receive abiraterone acetate and prednisone per standard of care for at least 6 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10 weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks for 6 months.

Antiandrogen Therapy, Abiraterone Acetate, and Prednisone With or Without Neutron Radiation Therapy in Treating Patients With Prostate Cancer

Radiation Enhancement of Local and Systemic Anti-Prostate Cancer Immune Responses

Percent change in peripheral blood effector T-cells will be calculated by measuring the difference of the percent peripheral blood effector T-cells for each patient between two time points: pre-treatment and post-treatment (3 months after start of ADT, which is also 1 month post-radiation in the radiation arm). Unpaired two-sample t-test or Wilcoxon rank-sum test, depending on distribution of the percent change, will be used to test the null hypothesis that the percent change in peripheral blood effector T-cells is equal between the two arms.

The number of patients with undetectable PSA at 6-months will be summarized by each arm and all combined.

Will be assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Safety and tolerability as evaluated by the incidence, severity, duration, causality, seriousness of adverse events. Toxicities will be summarized as the number of patients with grade 3 or higher toxicities per CTCAE v4.0, in addition to total number of toxicities (allowing for multiple toxicities within a patient) among all patients, and per treatment arm.

National Cancer Institute (NCI)

University of Washington

Professor

Patients are seen in clinic every 4 weeks during the 6 months period above, and adverse events are scored per CTCAE v4.0 per physician reported outcomes.

Patients receive ADT per standard of care. Beginning 2 months after start of ADT, patients also receive abiraterone acetate and prednisone per standard of care for at least 6 months in the absence of disease progression or unacceptable toxicity.

Antiandrogen Therapy: Undergo ADT

Abiraterone Acetate: Undergo Abiraterone Acetate Treatment SOC

Prednisone: Undergo Prednisone Treatment SOC

Arm I (ADT, Abiraterone, Prednisone)

Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10 weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease progression or unacceptable toxicity.

Antiandrogen Therapy: Undergo ADT

Abiraterone Acetate: Undergo Abiraterone Acetate Treatment SOC

Prednisone: Undergo Prednisone Treatment SOC

Radiation Therapy: Undergo neutron radiation therapy

Arm II (ADT, Abiraterone, Prednisone, Radiation Therapy)

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Early termination due to poor patient accrual leading to small numbers of subjects analyzed.

Dr. Jing Zeng

Clinical trial closed early due to poor accrual. Enrolled patient numbers are much lower than expected (10 out of 30 patients enrolled). There is no funding to run the assays to analyze the data since the trial failed to complete accrual. The original collaborators who were supposed to pay for the assays withdrew due to low patient numbers, and lack of ability to draw scientific conclusions from low patient numbers.

Percent Change in Peripheral Blood Effector T-cells (CCR7-/CD45RO)

Rate of Undetectable Prostate Specific Antigen (PSA) (< 0.2)

Incidence of Adverse Events

Overall Study

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Bendamustine Hydrochloride

Immunomodulating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients undergo leukapheresis to obtain PBMCs for T cell product manufacturing and may undergo bridging therapy at the discretion of the treating clinician on study. Patients then undergo lymphodepleting chemotherapy with cyclophosphamide IV and fludarabine IV on days -5, -4 and -33 or single agent bendamustine on days -4 and -3 at the discretion of the treating clinician and/or PI. Patients receive an autologous L1CAM-specific CAR+EGFRt+ T cells infusion on day 0. Based on disease response and persistence of CAR T cells, patients may receive additional lymphodepletion chemotherapy and an autologous L1CAM-specific CAR+EGFRt+ T cell infusion as soon as 6 weeks and no later than 24 weeks after the first infusion, or at the discretion of the PI. Patients also undergo ECHO or MUGA during screening. Patients undergo x-ray imaging, CT, bone scan, and blood sample collection throughout the trial. Additionally, patients may undergo tissue biopsy on the trial.

Bendamustine

Biopsy

Biospecimen Collection

Bone Scan

Bridge Therapy

Computed Tomography

Echocardiography

Leukapheresis

Multigated Acquisition Scan

Given autologous L1CAM-specific CAR+EGFRt+ T cells IV

T-cell Receptor-engineered T-cells

X-Ray Imaging

Fred Hutch Intake

Michael Schweizer

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ lentivirally transduced to express L1CAM-specific chimeric antigen receptor (CAR) and EGFRt mutation specific T cells and to see how well they work in treating patients with small cell neuroendocrine prostate cancer (SCNPC) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. Some solid tumor cells have an L1CAM protein on their surface, and T cells can be modified with a receptor, called a chimeric antigen receptor (CAR), to help recognize this protein and kill these tumor cells. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. These L1CAM mutation specific T cells may help the body's immune system identify and kill L1CAM locally advanced and unresectable or metastatic small cell neuroendocrine prostate cancers' tumor cells.

OUTLINE: This is a dose-escalation study of autologous L1CAM-specific CAR+EGFRt+ T cells.

Patients undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMCs) for T cell product manufacturing and may undergo bridging therapy at the discretion of the treating clinician on study. Patients then undergo lymphodepleting chemotherapy with cyclophosphamide intravenously (IV) and fludarabine IV on days -5, -4 and -33 or single agent bendamustine on days -4 and -3 at the discretion of the treating clinician and/or principal investigator (PI). Patients receive an autologous L1CAM-specific CAR+EGFRt+ T cell infusion on day 0. Based on disease response and persistence of CAR T cells, patients may receive additional lymphodepletion chemotherapy and an autologous L1CAM-specific CAR+EGFRt+ T cell infusion as soon as 6 weeks and no later than 24 weeks after the first infusion, or at the discretion of the PI. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients undergo x-ray imaging, computed tomography (CT), bone scan, and blood sample collection throughout the trial. Additionally, patients may undergo tissue biopsy on the trial.

After completion of study treatment, patients are followed up monthly for 3 months, then every 3 months up to 12 months then may undergo long-term follow-up annually for up to 15 years.

Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptors in Treating Patients With Locally Advanced and Unresectable or Metastatic Small Cell Neuroendocrine Prostate Cancer

A Phase I Safety and Feasibility Study of Cellular Immunotherapy for Extensive Stage Small Cell Neuroendocrine Prostate Cancer Using Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptor

The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0 and nadir or maximum values for the laboratory measures), date of onset and attribution. Tables will be created to summarize these toxicities and side effects by dose level.

The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 5.0 and nadir or maximum values for the laboratory measures), date of onset and attribution. Tables will be created to summarize these toxicities and side effects by dose level.

Will be determined using RECIST version 1.1 and will be summarized at each dose level, and the number and percent responding combined across dose levels.

Will be assessed using RECIST v 1.1 criteria for soft tissue metastases and Prostate Cancer Working Group 3 criteria. Survival and time to relapse/progression will be summarized both by pooling across dose levels and within each dose level. Will calculate survival curves and the median expected survival duration, using the Kaplan-Meier estimate.

Bristol-Myers Squibb

Fred Hutchinson Cancer Center

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Lung Neoplasms

Small Cell Lung Carcinoma

Recurrence

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Topotecan

Topoisomerase I Inhibitors

Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may crossover to Arm II at disease progression. Patients undergo a CT scan during screening and on study as well as a tumor biopsy during screening. Patients may also undergo blood sample collection during screening and on study.

Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5 and M6620 IV over 60 minutes on days 2 and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan during screening and on study as well as a tumor biopsy during screening. Patients may also undergo blood sample collection during screening and on study.

Berzosertib

Topotecan Hydrochloride

Anish Thomas

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.

PRIMARY OBJECTIVE:

I. To determine if the combination of berzosertib (M6620) with topotecan hydrochloride (topotecan) will result in an improvement in progression-free survival (PFS) compared to topotecan alone in patients with relapsed small cell lung cancer (SCLC).

SECONDARY OBJECTIVE:

I. To determine the objective response rate (ORR) and overall survival (OS) with the combination of M6220 and topotecan in patients with relapsed SCLC and extrapulmonary small cell cancers.

EXPLORATORY OBJECTIVES:

I. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to ribonucleic acid (RNA) sequencing (RNA-Seq):

Ia. To assess expression of genes Schlafen family member 11 (SLFN11), MYC, and ataxia-telangiesctasia mutated (ATM) among others.

Ib. To identify potential predictive biomarkers of response to a combination of M6620 with topotecan.

Ic. Identify mechanisms of drug sensitivity and resistance using deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.

II. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.

III. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the Early-Phase and Experimental Clinical Trials (EET) Biobank at Nationwide Children's Hospital.

IV. To characterize circulating cell-free DNA (cfDNA) and circulating tumor cells in patients with relapsed SCLC and extrapulmonary small cell cancers.

V. To identify potential predictive biomarkers of response to a combination of M6620 with topotecan in patients with extrapulmonary small cell cancers.

OUTLINE: Patients are randomized to 1 of 2 arms. Patients with extrapulmonary small cell cancer are assigned to Arm II while patients with relapsed small cell lung cancer are assigned to both arms.

ARM I: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes on days 1-5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may crossover to Arm II at disease progression. Patients undergo a computed tomography (CT) scan during screening and on study as well as a tumor biopsy during screening. Patients may also undergo blood sample collection during screening and on study.

ARM II: Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5 and M6620 IV over 60 minutes on days 2 and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan during screening and on study as well as a tumor biopsy during screening. Patients may also undergo blood sample collection during screening and on study.

After completion of study treatment, patients are followed up at 4 weeks and then every 12 weeks thereafter.

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

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

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

The combination of M6620 with topotecan will be compared to topotecan alone in patients with relapsed small cell lung cancer (SCLC). Kaplan-Meier curves and a one-tailed log-rank test will be the primary analysis methods.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Antiandrogen Therapy, Abiraterone Acetate, and Prednisone With or Without Neutron Radiation Therapy in Treating Patients With Prostate Cancer	NCT03649841	Castration-Sens... Metastatic Mali... Metastatic Pros... Prostate Adenoc... Prostate Small ... Stage IV Prosta... Stage IVA Prost... Stage IVB Prost...	Antiandrogen Th... Abiraterone Ace... Prednisone Radiation Thera...	18 Years -	University of Washington
Antiandrogen Therapy, Abiraterone Acetate, and Prednisone With or Without Neutron Radiation Therapy in Treating Patients With Prostate Cancer	NCT03649841	Castration-Sens... Metastatic Mali... Metastatic Pros... Prostate Adenoc... Prostate Small ... Stage IV Prosta... Stage IVA Prost... Stage IVB Prost...	Antiandrogen Th... Abiraterone Ace... Prednisone Radiation Thera...	18 Years -	University of Washington
Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptors in Treating Patients With Locally Advanced and Unresectable or Metastatic Small Cell Neuroendocrine Prostate Cancer	NCT06094842	Prostate Carcin... Prostate Small ... Stage III Prost... Stage IV Prosta...	Bendamustine Biopsy Biospecimen Col... Bone Scan Bridge Therapy Computed Tomogr... Cyclophosphamid... Echocardiograph... Fludarabine Leukapheresis Multigated Acqu... T-cell Receptor... X-Ray Imaging	18 Years -	Fred Hutchinson Cancer Center
Randomized Trial of Topotecan With M6620, an ATR Kinase Inhibitor, in Small Cell Lung Cancers and Small Cell Cancers Outside of the Lungs	NCT03896503	Bladder Small C... Extensive Stage... Extrapulmonary ... Limited Stage L... Platinum-Resist... Platinum-Sensit... Prostate Small ... Recurrent Lung ...	Berzosertib Biopsy Biospecimen Col... Computed Tomogr... Topotecan Hydro...	18 Years -	National Cancer Institute (NCI)
Randomized Trial of Topotecan With M6620, an ATR Kinase Inhibitor, in Small Cell Lung Cancers and Small Cell Cancers Outside of the Lungs	NCT03896503	Bladder Small C... Extensive Stage... Extrapulmonary ... Limited Stage L... Platinum-Resist... Platinum-Sensit... Prostate Small ... Recurrent Lung ...	Berzosertib Biopsy Biospecimen Col... Computed Tomogr... Topotecan Hydro...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for prostate small cell neuroendocrine carcinoma