Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Esophageal Neoplasms

Hypoxia

Esophageal Squamous Cell Carcinoma

Gastrointestinal Neoplasms

Death

Digestive System Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Immune Checkpoint Inhibitors

Pembrolizumab

Albumin-Bound Paclitaxel

Cisplatin

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Neoadjuvant setting (Pembrolizumab in combination with chemotherapy): Up to 4 cycles concurrent administrations of (1) Paclitaxel, which are administrated intravenously at 150 mg/m\^2 dosage on Day 1 of each 3-week cycle; (2) Cisplatin, which are administrated intravenously at 80 mg/m\^2 dosage on Day 1 of each 3-week cycle; (3) Pembrolizumab, which are administrated intravenously at 200 mg dosage on Day 1 of each 3-week cycle.

Adjuvant setting (Pembrolizumab in combination with chemotherapy): All participants who are assessed as ineligible or unnecessary for surgery after neoadjuvant treatment may be eligible for up to an additional 17 cycles (approximately 1 year) of Pembrolizumab treatment in combination with chemotherapy.

Biological: Pembrolizumab 200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Drug: Paclitaxel 150 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Drug: Cisplatin 80 mg/m\^2 administered IV Q3W on Day 1 of each 3-week cycle, up to 4 administrations in neoadjuvant setting.

Haiquan Chen, M.D., Ph.D.

Bin Li, M.D.

Chen Haiquan, MD

Bin Li, MD

The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and paclitaxel as neoadjuvant treatment in participants with locally advanced esophageal squamous cell carcinoma (ESCC), and to explore treatment resistance mechanisms.

The overall primary efficacy hypotheses are as follows:

In all eligible participants with locally advanced ESCC, pathologic complete response (pCR) rate is non-inferior with pembrolizumab plus SOC chemotherapy compared with historical benchmark.

The overall primary translational hypotheses are as follows:

Major hypoxia signals are significantly higher in baseline or post-treatment tumor samples from non-responders to pembrolizumab plus SOC chemotherapy, as compared to those samples from responders.

Pembrolizumab in combination with chemotherapy (Paclitaxel plus Cisplatin, TP regimen)

Pembrolizumab Plus Chemo in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma (Eastern Cooperative Thoracic Oncology Projects 2004, ECTOP-2004)

A Pilot Study of Hypoxia as a Potential Resistance Mechanism to PD-1 Checkpoint Blockade Therapy in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma (HYPERION)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Spatial proteomic measurement of hypoxia and defined cell lineages are assessed by multiplex IHC assay.

Single cell genomic measurement of hypoxia pathway genes are assessed by single cell RNA sequencing.

PCR is used as surrogate efficacy endpoint and is assessed by the Mandard tumor regression grade (TRG). PCR is defined as TRG1 plus no positive lymph node. PD-L1 expression is measured by 22C3 clone PD-L1 IHC assay followed by CPS scoring methods.

R0 resection is defined as microscopically margin-negative resection, without remaining gross or microscopic tumor in the primary tumor bed.

EFS is defined as time from allocation to any of the following events: progression of disease that precludes surgery, local or distant recurrence, a second primary tumor, or death due to any cause. PD-L1 expression is measured by 22C3 clone PD-L1 IHC assay followed by CPS scoring methods.

Pathologic complete response is used as surrogate efficacy endpoint and is assessed by the Mandard tumor regression grade (TRG). PCR is defined as TRG1 plus no positive lymph node.

Major hypoxia signals in tumor microenvironment (TME) are assessed by IHC methods, using tumor samples acquired pre- and post-treatment. Major hypoxia signals are to be compared between non-responders and responders to pembrolizumab plus SOC chemotherapy. In this neoadjuvant study, we define that patients who fail to reach major pathologic response (mPR) before surgery are classified as non-responders, and patients who reach mPR before surgery as responders. MPR is assessed by the Mandard TRG. MPR is defined as combined TRG1 and TRG2.

Pathologic complete response is used as surrogate efficacy endpoint and is assessed by the Mandard tumor regression grade (TRG). PCR is defined as TRG1 plus no positive lymph node. PD-L1 expression is measured by 22C3 clone PD-L1 IHC assay followed by combined positive score (CPS) scoring methods.

EFS is defined as time from allocation to any of the following events: progression of disease that precludes surgery, local or distant recurrence, a second primary tumor, or death due to any cause.

Lineage-specific hypoxia signals in TME are assessed by multi-color flow cytometry in defined immune subsets and tumor, using surgical tumor samples acquired post-treatment. Lineage-specific hypoxia signals are to be compared between non-responders and responders to pembrolizumab plus SOC chemotherapy. In this neoadjuvant study, we define that patients who fail to reach mPR before surgery are classified as non-responders, and patients who reach mPR before surgery as responders. MPR is assessed by the Mandard TRG. MPR is defined as combined TRG1 and TRG2.

Merck Sharp & Dohme LLC

Fudan University

Chief, Department of Thoracic Surgery

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Non-Small-Cell Lung

Urinary Bladder Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Carboplatin

Patients are eligible for this study if they have non-small cell lung cancer or bladder cancer and will receive cisplatin or carboplatin-based chemotherapy for the treatment of cancer. They will receive one microdose of C-14-carboplatin approximately 4 hours before scheduled biopsy/surgery. One blood draw and a few milligrams of leftover tumor tissue will be taken for analysis of carboplatin-DNA adduct levels. The dose of carboplatin will be about 1/100th the therapeutic dose.

Carbon-14-labeled carboplatin

Chong-xian Pan, MD, PhD

Carboplatin kills cancer cells mainly through induction of DNA damage (drug-DNA adducts). The goal of this clinical trial is to determine if chemoresistance to carboplatin can be identified by measuring carboplatin-induced DNA monoadducts, the precursor of Pt-DNA diadducts or crosslinks, from subtherapeutic drug doses given prior to the initiation of chemotherapy. We hypothesize that low levels of carboplatin-DNA monoadducts and rapid drug-DNA adduct repair correlate with chemoresistance. A highly sensitive technology, called accelerator mass spectrometry (AMS), will be used to measure carboplatin-DNA monoadducts from patient samples. AMS can measure C-14 at the attomole level in specimens of milligram size. In this study, patients will receive one non-toxic "microdose" (defined as 1/100th the therapeutic dose) of C-14-labeled carboplatin. Blood specimens will be drawn for determination of carboplatin-DNA monoadduct formation and repair in peripheral blood mononuclear cells (PBMC), and pharmacokinetics (PK) will be determined from serum ultrafiltrate. In patients microdosed prior to providing tumor samples, a few milligrams of leftover tumor biopsy/resection specimens will be analyzed for formation of carboplatin-DNA monoadducts. Patients will subsequently receive carboplatin-based chemotherapy. The levels of microdose-induced carboplatin-DNA monoadducts will be correlated with response to chemotherapy. Some blood and biopsy samples will be assayed by RT-PCR for several putative resistance markers at the mRNA level. Side effects will also be monitored and compared to the AMS data. This trial will also utilize PK, DNA repair and pharmacogenomics data in order to determine some of the underlying chemoresistance mechanisms.

Clinical Study of Microdosing Carboplatin in Lung or Bladder Cancer

A Phase 0 Clinical Trial of Microdosing Carboplatin and Molecular Profiling for Chemoresistance

Imaging studies (including CT, MRI, PET/CT and CXR) and cystoscopy will be performed to evaluate the response. The RECIST 1.1 will be used to determine the cancer response. Tumor response, including complete response (CR, or complete disappearance) or partial response (PR, at least a 30% decrease of target lesion) will be correlated with the patient's carboplatin-DNA monoadduct levels.

The half-life of carboplatin and the repair rate of DNA monoadducts (decrease of DNA monoadducts over 24 hours) in PBMC and tumor tissue will be determined and calculated. The ERCC1 expression levels will be determined with quantitative RT-PCR using beta-actin as the internal control. These parameters will be correlated with tumor response (CR or PR) to chemotherapy.

Lawrence Livermore National Laboratory

National Institutes of Health (NIH)

University of California, Davis

Prostatic Neoplasms

Neoplasm Metastasis

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

Androgens

Development the Predictive Nomogram for mCRPC in Patients with Prostate Cancer

Validation the Predictive Nomogram for mCRPC in Patients with Prostate Cancer

Shimiao Zhu, MD,PhD

Rong Han

Yuanjie Niu, MD,PhD

This is an observational, prospective (study following participants forward in time), multi-center (study conducted in more than 1 center) study to identify the risk factors, then develop and validate the predictive Nomogram of metastatic castration-resistant prostate cancer (mCRPC) that will effectively predict the early onset mCRPC in patients receiving androgen-deprivation therapy (ADT). The entire duration of study will be approximately 3 year. Participants will primarily be evaluated for achieving biochemical or radiological progression after receiving ADT based on EAU 2017 practice guideline criteria. Serum testosterone, prostate specific antigen (PSA), alkaline phosphatase (ALP) and blood routine will be monitored throughout the study.

Predictive Nomogram of CRPC

Development and Validation of Predictive Nomogram for Castration Resistant to Androgen Deprivation Therapy in Patients With Advanced Prostate Cancer

IPD could be got by contacting researchers.

The definition mCRPC is that the castrated androgen \< 50 ng/dL or 1.7 nmol/L plus either;

1. Biochemical progression: Three consecutive rises in PSA one week apart resulting in two 50% increases over the nadir, and a PSA \> 2 ng/mL or,
2. Radiological progression: The appearance of new lesions: either two or more new bone lesions on bone scan or a soft tissue lesion using RECIST (Response Evaluation Criteria in Solid Tumours) \[736\].

Symptomatic progression alone must be questioned and subject to further investigation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab Plus Chemo in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma (Eastern Cooperative Thoracic Oncology Projects 2004, ECTOP-2004)	NCT05281003	Esophageal Squa...	Pembrolizumab Paclitaxel Cisplatin	18 Years - 75 Years	Fudan University
Clinical Study of Microdosing Carboplatin in Lung or Bladder Cancer	NCT01261299	Carcinoma, Non-... Urinary Bladder...	Carbon-14-label...	18 Years -	University of California, Davis
Pembrolizumab Plus Chemo in Neoadjuvant Treatment of Esophageal Squamous Cell Carcinoma (Eastern Cooperative Thoracic Oncology Projects 2004, ECTOP-2004)	NCT05281003	Esophageal Squa...	Pembrolizumab Paclitaxel Cisplatin	18 Years - 75 Years	Fudan University
Predictive Nomogram of CRPC	NCT03177551	Castration-resi... Metastatic Canc...		18 Years -	Tianjin Medical University Second Hospital

Spots Global Cancer Trial Database for drug resistance, neoplasm