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)

Micronutrients

Hematinics

Vitamins

Leucovorin

Fluorouracil

Irinotecan

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Patients will receive FOLFIRI every 2 weeks: Irinotecan 180mg/m2 IV over 90 minutes on Day 1; Leucovorin IV over 2 hours on Day 1(l-LV 200 mg/m2 or dl-LV 400 mg/m2 ); 5-Fluorouracil 400 mg/m2 IV bolus on Day 1; followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion.

FOLFIRI

Li Yuhong, Ph D

This phase Ⅱ study was designed to evaluate the efficacy and safety of FOLFIRI as second-line treatment for metastatic esophageal carcinoma.

Although there are no standard second-line treatment for metastatic esophageal carcinoma, some studies have showed that irinotecan, fluorouracil may be effective in treating patients with metastatic esophageal carcinoma after failure of first-line treatment. Since irinotecan, fluorouracil, and leucovorin work in different ways to stop the growth of tumor. Giving more than one drug may be more effective. In this phase Ⅱ trial, the investigator would like to observe the efficacy and safety of FOLFIRI(Irinotecan/5-FU/leucovorin ) as second-line treatment for metastatic esophageal carcinoma.

FOLFIRI as Second Line Chemotherapy for Metastatic Esophageal Carcinoma

Phase Ⅱ Study of FOLFIRI as Second-Line Chemotherapy for Metastatic Esophageal Carcinoma

Safety profile will be assessed using the NCI CTCAE version 3.0

Yuhong Li

MD,Ph D

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Nimotuzumab

Antineoplastic Agents, Immunological

irinotecan 180mg/m2，iv ，d1，LV 200 mg/m2 ，2h，d1，5-FU 400 mg/m2， iv，d1 5-FU 2400mg/m2，CIV，46h，q2w Nimotuzumab 200mg，iv，qw

mFOLFIRI+Nimotuzumab

xiaodong zhang, MD

XIAODONG ZHANG, MD

There are few studies about 2nd line treatment in advanced esophageal carcinoma (AEC), some showed that irinotecan may be effective. The investigators previous study has shown the efficacy and safety of paclitaxel/cisplatin as 1st line treatment, so in this phase II study, the investigators would like to observe the efficacy and safety of Nimotuzumab plus Irinotecan/5FU/leucovorin as 2nd line treatment if AEC after failure to 1st treatment of PTX/DDP.

mFOLFIRI Combine With Nimotuzumab Second Line Chemotherapy for Squamous-cell Carcinoma of the Esophagus

Peking University

HEAD OF GI ONCOLOGY

Paclitaxel

Albumin-Bound Paclitaxel

mFOLFIRI irinotecan 130-150mg/m2 iv d1 LV 200 mg/m2 iv 2h d1 5-FU 400 mg/m2 IV d1 5-FU 2.4-3 g/m2 CI 46-h repeat every 2 weeks

mFOLFIRI

zhang xiaodong, MD

zhang xiaotian, MD

shen lin, MD

There are few studies about 2nd line treatment in advanced esophageal carcinoma(AEC), some showed that irinotecan may be effective. The investigators previous study has shown the efficacy and safety of paclitaxel/cisplatin as 1st line treatment, so in this phase II study, the investigators would like to observe the efficacy and safety of Irinotecan/5FU/leucovorin as 2nd line treatment if AEC after failure to 1st treatment of PTX/DDP.

mFOLFIRI as the Second Line Chemotherapy for Advanced Esophageal Carcinoma After Failure of 1st Line Treatment of Paclitaxel/DDP : a Phase II Single Center Prospective Clinical Trial

zhang xiaodong

Neoplasms, Squamous Cell

guibin Qiao, MD

Guibin Qiao, MD

Conduct a retrospective and prospective study to confirm the association between blood cells counts and the efficacy and safety in immunochemotherapy in patients with advanced esophageal cancer.

Studies have already demonstrated the feasibility of prognostic role of protein biomarkers change during the treatment trajectory of patients in several carcinoma,However, no study focused on the value of trajectory analysis of blood cells counts of Immunochemotherapy in patients with advanced esophageal cancer.

The investigators plan to analyze the dynamic change of blood cells counts longitudinally from preoperation to long term follow-up in advanced esophageal cancer and predict the efficacy and safety of immunochemotherapy.

Blood cell counts recorded at baseline and after the first cycle of treatment

Trajectory Analysis of NLR and Its Association With Efficacy of Immunochemotherapy in ESCC.

Trajectory Analysis of Neutrophil to Lymphocyte Ratio（NLR） and Its Association With Efficacy of Immunochemotherapy in Esophageal Squamous Cell Carcinoma: A Retrospective Cohort Study

The rate of pathologic complete response rate after the combined treatment of chemotherapy and immunotherapy following surgery

Immune-modified Response Evaluation Criteria In SolidTumors (iRECIST) criteria defined complete response and partial response

ess than 10% residual viable tumor follow neoadjuvant therapy

Guangdong Provincial People's Hospital

Professor of Medicine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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)
FOLFIRI as Second Line Chemotherapy for Metastatic Esophageal Carcinoma	NCT02023593	Advanced Esopha...	FOLFIRI	18 Years - 75 Years	Sun Yat-sen University
mFOLFIRI Combine With Nimotuzumab Second Line Chemotherapy for Squamous-cell Carcinoma of the Esophagus	NCT01486992	Advanced Esopha...	mFOLFIRI+Nimotu...	18 Years - 75 Years	Peking University
mFOLFIRI as the Second Line Chemotherapy for Advanced Esophageal Carcinoma After Failure of 1st Line Treatment of Paclitaxel/DDP : a Phase II Single Center Prospective Clinical Trial	NCT01044420	Advanced Esopha...	mFOLFIRI	18 Years - 70 Years	Peking University
mFOLFIRI Combine With Nimotuzumab Second Line Chemotherapy for Squamous-cell Carcinoma of the Esophagus	NCT01486992	Advanced Esopha...	mFOLFIRI+Nimotu...	18 Years - 75 Years	Peking University
Trajectory Analysis of NLR and Its Association With Efficacy of Immunochemotherapy in ESCC.	NCT06125262	Esophageal Squa... Immunotherapy Chemotherapy		-	Guangdong Provincial People's Hospital

Spots Global Cancer Trial Database for advanced esophageal carcinoma