Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Esophageal Neoplasms

Esophageal Squamous Cell Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Raltitrexed

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Enzyme Inhibitors

Folinic Acid

Folate

Vitamin B9

Raltitrexed 2.6mg/m2 was administered on d1、d22

raltitrexed

Concurrent chemoradiotherapy is one of the curative options for esophageal squamous cell carcinoma. We evaluated the efficacy and toxicity of raltitrexed with concurrent radiotherapy in elderly patients with esophageal cancer.

Raltitrexed Concurrent With Radiotherapy for Elderly Chinese Patients With Squamous Cell Carcinoma of Esophagus

Raltitrexed Concurrent With Radiotherapy for Elderly Chinese Patients With Squamous Cell Carcinoma of Esophagus: A Phase-II Study

From the date of randomization until the date of death

From the date of randomization to the date of first observation of disease progression, or relapse, or death due to any cause

Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCICTC), version 3.0

QOL is respectively evaluated at randomization and 1 month, 3 month, 6 month and yearly after treatment among patients by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30)

Huai'an First People's Hospital

Symptoms and General Pathology

Adenocarcinoma

Pathologic Complete Response

Disease Progression

Disease Attributes

Anti-Infective Agents

Itraconazole

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Itraconazole capsule 300mg twice daily for 6-8 weeks following chemoradation.

Oral administration of itraconazole twice daily from completion of neoadjuvant chemoradiation until esophagectomy.

David Wang, MD, PhD

Thai Pham, MD

Jessica Vallejo, BSA

Esophageal cancer, which has a low 5-year overall survival rate for all stages (\<20%) , is increasing in incidence. Previous studies have shown that the Hedgehog (Hh) and AKT signaling pathways are activated in a significant proportion of esophageal cancers. Itraconazole, a widely used anti-fungal medication, has been shown to inhibit various pathways involved in esophageal cancer tumorigenesis including Hh and AKT. In this phase II clinical trial, the investigators aim to evaluate the effect of itraconazole as a neoadjuvant therapy following standard of care chemoradiation in the treatment of locoregional esophageal and gastroesophageal junction carcinomas.

Esophageal cancer has a high incidence rate in the United States, and novel approaches to its treatment are being studied. Itraconazole, an antifungal agent, has been shown to inhibit the Hedgehog (Hh) and AKT signaling pathways, which are upregulated in esophageal cancer and promote tumor cell growth. This study will evaluate whether the use of itraconazole leads to increased rates of pathological complete response (pathCR) by at least 15% from the historical pathCR rate of 25% in patients with esophageal cancer or gastroesophageal junction (GEJ) adenocarcinoma. The investigators will enroll approximately 78 patients with esophageal cancer or GEJ adenocarcinoma who will then undergo standard of care staging work-up with a PET/CT and endoscopic ultrasound (EUS). In a subset of patients, biopsies will be obtained to assess the status of the Hh and AKT signaling pathways by PCR, Western blot, and immunohistochemistry in the primary tumor before treatment. If no distant metastases are found, all patients will undergo 5-6 weeks of standard of care neoadjuvant chemoradiation. Following this, all patients will be given itraconazole 300 mg twice daily for 6-8 weeks. Adverse effects to itraconazole will be monitored in oncology clinic. If standard restaging PET/CT following neoadjuvant chemoradiation does not reveal new metastases, the patient will undergo an esophagectomy. Samples from normal esophageal tissue will be analyzed for presence of itraconazole and its metabolites to determine if the patients were taking the study drug. Tumor tissue will be evaluated for status of Hh pathway activation, AKT and VEGFR2 phosphorylation, Ki67 immunostaining, and other molecular pathways with comparisons made to pre-treatment biopsies if available. The final pathology report will indicate whether the patient has achieved pathCR. Because the Hh signaling pathway is a resistance pathway that can be upregulated in response to chemoradiation, the investigators believe that administering itraconazole following neoadjuvant chemoradiation will lead to a higher pathCR rate. This in turn should be able to improve treatment outcomes in patients with esophageal cancer and GEJ adenocarcinoma.

Evaluating the Effect of Itraconazole on Pathologic Complete Response Rates in Esophageal Cancer

A Phase II Trial Evaluating the Effectiveness of Itraconazole in Improving Pathologic Complete Response Rates in Patients With Esophageal Cancer Through Inhibition of the Hedgehog and AKT Signaling Pathways

Generally for esophageal cancer the pathological complete response rate at time of esophagectomy is 25%, and we have designed our study with the projected number of patients assuming we observe an improvement of 15% or more in this rate following treatment with itraconazole. This is the study's primary endpoint. By inhibiting the Hh signaling pathway with the use of itraconazole, we anticipate improved pathological complete response rates.

As part of clinical staging, patients will undergo endoscopic ultrasound (EUS) following a PET/CT that does not show metastases. During EUS, some patients will undergo eight research biopsies obtained with large forceps for research purposes at the level of the visualized esophageal mass or abnormality (3 for RNA isolation, 3 for protein isolation, and 2 for formalin fixation). Three research biopsies for RNA isolation will also be obtained from normal appearing esophagus, at least 5 cm away from any mass lesions. The research biopsies will be submitted to qPCR analysis for mRNA expression levels of SHH, IHH, PTCH, GLI1, GLI2, and GLI3 (Hedgehog pathway components). Comparisons will be made between mass biopsies and normal esophageal tissues. Following esophagectomy, tissues will be analyzed for the aforementioned hedgehog pathway markers to determine response to therapy.

Tissue obtained prior to initiation of chemoradiation will be analyzed with Western blot to quantify presence of VEGFR2 and AKT. These markers will again be analyzed following esophagectomy to determine response to therapy.

The concentration of itraconazole and hydroxy-itraconazole in normal esophageal tissue will be measured following esophagectomy to ensure that the drug has been taken consistently.

Dallas VA Medical Center

Staff Physician

Amino Acids

Palbociclib

Afatinib

Protein Kinase Inhibitors

Tyrosine Kinase Inhibitors

Tyrosine

The first 6 enrolled patients were treated with Palbociclib 125 mg po qd on day 1 to 21, Afatinib 40 mg po qd on day 1 to 14, every 28 days as a cycle; If there are ≥ 2 cases of dose-limiting toxicity (DLT), the following 6 patients will reduce the dose to Palbociclib 125mg po qd on day 1 to 21, Afatinib 30mg po qd on day 1 to 28, every 28 days as a cycle; If ≥ 2 cases of DLT occur again, the following 6 patients will reduce the dose to Palbociclib 100mg po qd on day 1 to 21, Afatinib 30mg po qd on day 1 to 28, every 28 days as a cycle; If ≥ 2 cases of DLT occur again, we will analyze the characteristics of adverse events and determine the subsequent dose.

120mg/125mg po qd on day 1 to 21, every 28 days

30mg/40mg po qd on day 1 to 28, every 28 days

Aiping Zhou, MD

This is a prospective, multicenter, exploratory study. Patients with advanced esophageal or gastro-esophageal junction squamous carcinoma who had progressed on first-line chemotherapy combined with immune checkpoint inhibitors were treated with CDK4/6 inhibitor Palbociclib combined with Afatinib. Dose titration was used to determine the final dose, and objective antitumor efficacy was evaluated every 2 cycles (8 weeks +/- 7 days) according to RECIST 1.1 criteria, until tumor progression, intolerable toxicity, death, or withdrawal of informed consent. The primary endpoint is the objective response rate (ORR).

Palbociclib Combined With Afatinib for Advanced Squamous Carcinoma of Esophagus or Gastroesophageal Junction

CDK4/6 Inhibitor Palbociclib Combined With Afatinib as Second-line Treatment for Advanced Squamous Carcinoma of the Esophagus or Gastroesophageal Junction Progressed on at Least First-line Chemotherapy: a Phase 2 Trial

AIPING ZHOU

Vice director of Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

Neoplasm Metastasis

Squamous Cell Carcinoma of Head and Neck

Immunomodulating Agents

Patients with a histological or cytological confirmed diagnosis of Squamous Cell Cancer of the Head \& Neck, Esophagus or Anal Canal who have radiologically confirmed recurrent or metastatic disease and are commencing on a new treatment or either first-line platinum based chemotherapy or any line immunotherapy.

Elena Elimova, MD

This is prospective research study which will include patients with recurrent or metastatic squamous cell carcinoma of the head and neck, esophagus and anal canal starting on first-line platinum based chemotherapy or any line of immunotherapy treatment.This study aims to characterize the dynamic changes in genomic, epigenetic, immune profiling and imaging data during treatment with systemic therapy. Patients will have archived tumor samples requested as well as blood samples collected at up to four time points to analyze these changes. Imaging data will be derived from patients' routine CT scans before and after treatment.

Peripheral blood samples collected serially for DNA extraction under the LIBERATE protocol. Archived tumor samples collected for DNA extraction.

Multi-Omic Assessment of Squamous Cell Cancers Receiving Systemic Therapy

To comprehensively characterize genomic, epigenetic and immune profiling features and changes in longitudinal blood samples that are associated with systemic treatment of recurrent or metastatic squamous cell cancers of the head \& neck, esophagus and anal canal.

To establish a clinically annotated biorepository of archived tumor and longitudinal blood samples, with serial radiomic evaluations in patients with recurrent/metastatic squamous cell cancers commencing on any new systemic treatments.

To correlate genomic, othr-omic, radiomic and immune profiling results with clinical outcome - to identify potential predictive markers of response/resistance to systemic therapy.

To compare HPV-positive and HPV-negative squamous cell histology across three disease sites with multi-omic assessment.

To investigate whether any correlation or relation exists between tumor genomic profiles and radiomic imaging signatures.

To enable data sharing with Queen's University Belfast as a collaborative initiative based on this project

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Raltitrexed Concurrent With Radiotherapy for Elderly Chinese Patients With Squamous Cell Carcinoma of Esophagus	NCT03585530	Esophagus Squam...	raltitrexed	70 Years - 85 Years	Huai'an First People's Hospital
Evaluating the Effect of Itraconazole on Pathologic Complete Response Rates in Esophageal Cancer	NCT04018872	Esophagus Adeno... Esophagus Squam... Gastroesophagea...	Itraconazole	18 Years -	Dallas VA Medical Center
Palbociclib Combined With Afatinib for Advanced Squamous Carcinoma of Esophagus or Gastroesophageal Junction	NCT05865132	Esophagus Squam...	Palbociclib Afatinib	18 Years - 75 Years	Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Evaluating the Effect of Itraconazole on Pathologic Complete Response Rates in Esophageal Cancer	NCT04018872	Esophagus Adeno... Esophagus Squam... Gastroesophagea...	Itraconazole	18 Years -	Dallas VA Medical Center
Multi-Omic Assessment of Squamous Cell Cancers Receiving Systemic Therapy	NCT03712566	Cancer Esophagus Squam... Squamous Cell C... Anal Canal Squa... Metastatic Canc...		18 Years -	University Health Network, Toronto
Evaluating the Effect of Itraconazole on Pathologic Complete Response Rates in Esophageal Cancer	NCT04018872	Esophagus Adeno... Esophagus Squam... Gastroesophagea...	Itraconazole	18 Years -	Dallas VA Medical Center

Spots Global Cancer Trial Database for esophagus squamous cell carcinoma