Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Digestive System Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Rare Diseases

Uterine Cervical Neoplasms

Esophageal Neoplasms

Carcinoma

Small Cell Lung Carcinoma

Cholangiocarcinoma

Breast Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma, Transitional Cell

Stomach Neoplasms

Carcinoma, Small Cell

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Ductal

Mesothelioma

Mesothelioma, Malignant

Endometrial Neoplasms

Bile Duct Neoplasms

Penile Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Uterine Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Adenoma

Neoplasms, Mesothelial

Pleural Neoplasms

Biliary Tract Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Adenocarcinoma

Head and Neck Neoplasms

Esophageal Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Genital Neoplasms, Male

Genital Diseases, Male

Penile Diseases

Male Urogenital Diseases

Esophageal Cancer

Small Cell Lung Cancer

Ovarian Cancer

Transitional Cell Carcinoma

Bile Duct Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Malignant Mesothelioma

Penile Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Antimetabolites

Patients receive cisplatin IV over 1-2 hours on day 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive cisplatin IV over 1-2 hours on day 1 and 8, gemcitabine IV over 30 minutes on days 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Elimusertib

Gemcitabine Hydrochloride

Mamta Parikh

This phase I trial identifies the best dose, possible benefits and/or side effects of BAY 1895344 in combination with chemotherapy in treating patients with solid tumors or urothelial cancer that has spread to other places in the body (advanced). BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cisplatin and gemcitabine are chemotherapy drugs that stop the growth of tumor cells by killing the cells. Combining BAY 1895344 with chemotherapy treatment (cisplatin, or cisplatin and gemcitabine) may be effective for the treatment of advanced solid tumors, including urothelial cancer.

PRIMARY OBJECTIVES:

I. To establish the safety and tolerability of the combination of cisplatin + elimusertib (BAY 1895344) in patients with advanced solid tumors.

II. To establish the safety and tolerability of the combination of cisplatin + gemcitabine + BAY 1895344 in patients with advanced solid tumors with an emphasis on urothelial carcinoma (UC).

III. To establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of cisplatin + BAY 1895344 and cisplatin + gemcitabine + BAY 1895344.

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetic profile of BAY 1895344 (in the doublet and triplet combinations) and gemcitabine (in the triplet) in combination with cisplatin.

II. To further evaluate the toxicity of the combination of cisplatin + gemcitabine + BAY 1895344 in patients with UC.

III. To evaluate preliminary efficacy observed with cisplatin + BAY 1895344 and cisplatin + gemcitabine + BAY 1895344 in patients with advanced solid tumors, including UC.

IV. To monitor for tumor response and symptom relief in addition to safety and tolerability.

V. To evaluate the association between ATM expression by immunohistochemical staining and responses to therapy.

EXPLORATORY OBJECTIVES:

I. To evaluate the correlation of biomarkers, including deleterious deoxyribonucleic acid (DNA) damage response (DDR) gene alterations and circulating tumor (ct)DNA with responses to therapy using whole exome sequencing (WES) and messenger ribonucleic acid sequencing (RNA seq) analysis of archival formalin fixed paraffin embedded (FFPE) tissue, as well as blood.

II. To correlate drug exposure with response and/or toxicity.

OUTLINE: This is a dose-escalation study of elimusertib. Patients are assigned to 1 of 2 arms.

ARM I (DOUBLET COMBINATION): Patients receive cisplatin intravenously (IV) over 1-2 hours on day 1 and 8, and elimusertib orally (PO) once daily (QD) on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

ARM II (TRIPLET COMBINATION): Patients receive cisplatin IV over 1-2 hours on day 1 and 8, gemcitabine IV over 30 minutes on days 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months thereafter.

Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer

A Phase 1 Trial of the ATR Inhibitor BAY 1895344 in Combination With Cisplatin and With Cisplatin Plus Gemcitabine in Advanced Solid Tumors With an Emphasis on Urothelial Carcinoma

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.

Toxicities will be tabulated and reported according to dose level, grade, type, cycle, and attribution. Tables will be created to summarize these toxicities and side effects, overall and by cohort. Proportions and associated 95% confidence intervals will be calculated for each cohort separately. Cumulative incidence curves will be used to estimate the proportion of patients who will discontinue therapy for reasons of toxicity or general inability to tolerate the regimen.

Estimated using non-compartmental methods. The PK variables will be tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) calculated for each dose level. PK parameters will be reported descriptively for exploratory comparison with historical data (gemcitabine).

Estimated using non-compartmental methods. The PK variables will be tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) calculated for each dose level. PK parameters will be reported descriptively for exploratory comparison with historical data (gemcitabine). The impact of cisplatin on BAY 1895344 exposure will be evaluated by calculation of the AUC ratio of (day 9 / day 2) and testing non-parametrically with a null hypothesis of a ratio = 1.

The association between DDR mutations and responses will be described, with a table outlining patients who achieved by progressive disease, stable disease, partial or complete responses and DDR mutation status.

The association between ATM and responses will be described, with a table outlining patients who achieved progressive disease, stable disease, partial or complete responses and whether they exhibited ATM expression by immunohistochemistry (IHC) or not.

The percent of responders will be calculated and associated exact 95% confidence intervals will be constructed.

Kaplan-Meier plots will be used to summarize PFS.

National Cancer Institute (NCI)

Gallbladder Neoplasms

Gallbladder Diseases

Biliary Tract Cancer

Gallbladder Cancer

Anti-Infective Agents

Irinotecan

Trifluridine

Camptothecin

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antiviral Agents

Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Irinotecan Hydrochloride

Trifluridine and Tipiracil Hydrochloride

Amit Mahipal

This phase II trial studies how well trifluridine/tipiracil and irinotecan work in treating patients with biliary tract cancer that has spread to other places in the body (advanced) and has not responded to treatment (refractory). Trifluridine/tipiracil and irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. Determine the efficacy of trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) in combination with irinotecan hydrochloride (irinotecan) in patients with refractory biliary tract cancers using progression-free survival (PFS) at 16 weeks.

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers through adverse event monitoring.

II. Further explore the efficacy of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers by overall response rates (ORR), disease control rates (DCR), and overall survival (OS).

CORRELATIVE RESEARCH:

I. To determine if the number of circulating tumor cells (CTCs) or the level of cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline is prognostic or predictive to the response to therapy.

II. To determine if changes in CTCs or cfDNA correlate with efficacy endpoints. III. To determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine/tipiracil plus irinotecan.

IV. To evaluate the role of thymidine kinase 1 (TK1) in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.

EXPLORATORY RESEARCH:

I. To evaluate patients who received prior treatment with fluorouracil (5-FU) independently from the entire population in the following areas: PFS, safety and tolerability, ORR, DCR, and OS.

OUTLINE:

Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and irinotecan hydrochloride (IV) over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 2 years after study registration.

Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer

Phase II Trial of Trifluridine/Tipiracil in Combination With Irinotecan in Biliary Tract Cancers

Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.

Will determine if change in CTCs or cfDNA will correlate with efficacy endpoints.

Will determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) plus irinotecan hydrochloride (irinotecan).

Will evaluate the role of TK1 in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.

Will be defined as the proportion of evaluable patients who are progression-free (stable disease, partial response, complete response) at 16 weeks and assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Will be defined as the proportion of patients who experience either a partial response or complete response as their best response. ORR will be reported descriptively and a 95% confidence interval will be reported.

Will be defined as the proportion of patients who experience a partial response, complete response, or have stable disease as their best response. DCR will be reported descriptively and a 95% confidence interval will be reported.

Will be determined based on RECIST v 1.1. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported. Patients will be censored at the last disease assessment date.

Will be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported. Patients will be censored at the date patient was last known to be alive.

The maximum grade for each type of adverse event by patient will be summarized by frequencies and percentages using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

National Comprehensive Cancer Network

Mayo Clinic

Trifluridine and Tipiracil Hydrochloride: Given PO

Treatment (Trifluridine and Tipiracil, Irinotecan)

Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.\>

\> Irinotecan: Given IV\>

\> Irinotecan Hydrochloride: Given IV\>

\> Trifluridine and Tipiracil Hydrochloride: Given PO

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Prior treatment

Extrahepatic biliary tract cancer

Gallbladder

Intrahepatic

Primary Site of Tumor

Moderately

Poorly differentiated

Degree of differentiation

ECOG = 0: Fully active, able to carry on all pre-disease performance without restriction.

ECOG = 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.

ECOG = 0 is better. ECOG = 1 is worse.

ECOG Performance Status (PS)

Prior treatment with fluoropyrimidine based regimen

Bone

Liver

Peritoneum

Lung

Nodal

Abdominal Wall

Interaortocaval LN

Pancreas

Perisplenic and Perihepatic

Soft tissue, adrenal gland.

abdominal wall, mesenteric node.

hepatic duct

Metastatic Sites

Cholangiocarcinoma, intrahepatic and extrahepatic bile ducts (adenocarcinoma)

Gall Bladder Carcinoma

MedDRA disease code

Dr. Amit Mahipal

Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

\>

\> Irinotecan: Given IV

\>

\> Irinotecan Hydrochloride: Given IV

\>

\> Trifluridine and Tipiracil Hydrochloride: Given PO

Progression-free Survival (PFS)

7 patients went off treatment early on and weren't evaluated for response post-baseline

Overall Response Rate (ORR)

Disease Control Rate (DCR)

Overall Survival (OS)

Grade 3+ AE

Grade 4 AE

Grade 5 AE

Number of Participants With Adverse Events

Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (cfDNA) at Baseline

Change in CTCs or cfDNA

Correlation of Response

Prediction of Clinical Benefit by Thymidine Kinase 1 (TK1)

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer	NCT04491942	Advanced Bile D... Advanced Breast... Advanced Cervic... Advanced Endome... Advanced Esopha... Advanced Gastri... Advanced Head a... Advanced Lung N... Advanced Lung S... Advanced Malign... Advanced Ovaria... Advanced Penile... Advanced Pleura... Advanced Urothe... Anatomic Stage ... Anatomic Stage ... Clinical Stage ... Clinical Stage ... Stage III Cervi... Stage III Dista... Stage III Intra... Stage III Lung ... Stage III Ovari... Stage III Penil... Stage III Pleur... Stage IV Cervic... Stage IV Distal... Stage IV Intrah... Stage IV Lung C... Stage IV Ovaria... Stage IV Penile... Stage IV Pleura... Triple-Negative... Unresectable Ur...	Cisplatin Elimusertib Gemcitabine Hyd...	18 Years -	National Cancer Institute (NCI)
Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer	NCT04072445	Advanced Bile D... Advanced Gallbl... Refractory Bile... Refractory Gall... Stage III Dista... Stage III Gallb... Stage III Intra... Stage IIIA Dist... Stage IIIA Gall... Stage IIIA Intr... Stage IIIB Dist... Stage IIIB Gall... Stage IIIB Intr... Stage IV Distal... Stage IV Gallbl... Stage IV Intrah... Stage IVA Gallb... Stage IVB Gallb...	Irinotecan Irinotecan Hydr... Trifluridine an...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for stage iii intrahepatic bile duct cancer ajcc v8