Neoplasms

Symptoms and General Pathology

All Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Neoplasm Metastasis

Carcinoma

Recurrence

Nasopharyngeal Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Anti-Infective Agents

Antirheumatic Agents

All Drugs and Chemicals

Hydroxychloroquine

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Hydroxychloroquine (HCQ), is used one day before chemotherapy and radiotherapy, 400-600mg, oral tablet, once. During chemotherapy and radiotherapy, HCQ maintenance dose is 200-400mg daily.

Placebos are used one day before chemotherapy and radiotherapy, and during the therapy.

HCQ, 400-600mg, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, HCQ maintenance dose is 200-400mg daily.

Placebo, oral tablet, once, one day before chemotherapy and radiotherapy. During therapy, placebo maintenance oral tablet once daily.

Placebo

Bo You, Doctor

Dormant cancer cells that survive anti-cancer therapy can lead to cancer recurrence and disseminated metastases that prove fatal in most cases. Recently, specific dormant polyploid giant cancer cells (PGCC) have drawn our attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In study, we report the biological properties of PGCC, and reveal that autophagy is a critical mechanism of PGCC induction. Moreover, pharmacological inhibition of autophagy greatly impaired PGCC formation, significantly suppressing metastasis and improving survival in a mouse model. Mechanistically, chemotherapeutic drugs partly damaged mitochondria, and activated autophagy to promote PGCC formation. High numbers of PGCCs correlated with shorter recurrence time and worse survival outcomes in NPC patients. Collectively, these findings suggest a therapeutic approach of targeting dormant PGCCs in cancer.

Pretreatment with an autophagy inhibitor (HCQ) before chemotherapy and radiotherapy could prevent formation of therapy-induced dormant polyploid giant cancer cells, thereby reducing recurrence and metastasis of nasopharyngeal carcinoma.

Although the majority of patients with nasopharyngeal carcinoma (NPC) do not present with overt metastases at diagnosis, a significant number succumb to disseminated disease years after the successful treatment of the primary tumor. Thus, late NPC recurrence may be the result of rare and elusive dormant cancer cells hiding in specialized niches being reactivated by specific signals. The concept of cancer dormancy has been described for the most common solid and hematological cancers; however, the dormant cancer cells in NPC remain largely uncharacterized.

Although many factors contribute toward cancer cell dormancy, recent studies have demonstrated that cancer therapy can induce cellular dormancy. Indeed, therapy-induced dormancy has been shown to lead to durable proliferation arrest, resulting in the formation of polyploid giant cancer cells (PGCCs), which are a unique sub-population of cancer cells that contribute toward the heterogeneity of solid tumors. Unlike regular-sized diploid cancer cells, PGCCs display distinct morphological features, including a large cytoplasmic area and a high genomic content contained within a single highly enlarged nucleus or multiple nuclei. Despite being present in low numbers, the frequency of PGCCs increases markedly after exposure to hypoxia and therapeutic interventions such as radiotherapy and chemotherapies.

Our findings, which used a highly relevant clinical orthotopic model of imageable NPC and clinical data, suggest that autophagy inhibition (HCQ) prevents therapy-induced dormant PGCC formation and thereby prevents NPC metastasis.

Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients

Study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code will be shared to other researchers.

After the patients are diagnosed and treated, CT scans is used semi-annually to determine the progression, recurrence and metastasis of tumor.

Affiliated Hospital of Nantong University

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Erlotinib 150 mg oral daily plus Hydroxychloroquine (HCQ) 1000 mg oral daily

Erlotinib

1000 mg taken orally once daily after erlotinib

Lecia Sequist, MD

The purpose of this research study is to learn if adding hydroxychloroquine (HCQ) to erlotinib helps treat non-small cell lung cancer (NSCLC). Another goal of this research study is to learn more about NSCLC and how it may respond to study treatment. Erlotinib (Tarceva) is a type of drug called a tyrosine kinase inhibitor (TKI). TKIs block a protein called the epidermal growth factor receptor (EGFR). EGFR may control tumor growth and tumor cell survival. However, although TKI drugs can work for some lung cancer patients for a period of time, eventually the tumor finds a way to resist or counteract the TKI treatment and it begins to grow again. Hydroxychloroquine (HCQ) is a drug approved by the FDA for treating malaria, rheumatoid arthritis, and several other diseases. Laboratory research suggests that when HCQ is given with a TKI, it may help delay or prevent TKI resistance from developing.

* Because no one knows which of the study options are best, participants will be randomized into of the study groups: Group A (erlotinib) or Group B (erlotinib and HCQ). Study treatment will be divided into time periods called cycles. Each study treatment cycle is 28 days.
* Erlotinib (Group A and Group B) will be taken orally once a day. Hydroxychloroquine (Group B) will be taken orally once a day after taking erlotinib.
* The following tests and procedures will be performed day 1 of each cycle: physical examination, performance status assessment, questions about any symptoms or side effects, blood for routine tests. The following procedures will be performed at certain study visits: Research blood tests (cycle 1, cycle 2, then every other even cycle); eye exam (cycle 4, cycle 7, and then every 3 months); assessment of the tumor with CT or MRI scan (done at the end of even cycles.

Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations

Phase II Study of Erlotinib With or Without Hydroxychloroquine in Patients With Previously Untreated Advanced NSCLC and EGFR Mutations

Serial circulating tumor cell (CTC) analyses will be performed on peripheral blood and correlated with disease response.

Correlation of molecular and genetic tumor characteristics with disease response. Genomic DNA will be extracted from tumor tissue and direct sequencing analysis will be performed to identify additional mutations.

\[18F\]-FMISO-PET/CT was performed on a 64-slice PET/CT scanner and tracer uptake was assessed using SUV (standardized uptake value), normalizing the radioactivity measured in tissue by the injected dose and the body weight of the patient. Mean and maximum SUV and threshold volume of FMISO uptake were measured to quantify the extent of hypoxia in the primary tumor. Imaging was performed before and after initiation of therapy with erlotinib.

A measure of progression-free survival in patients with advanced non small-cell lung cancer (NSCLC) and EGFR mutations treated with erlotinib as compared with patients treated with erlotinib plus hydroxychloroquine (HCQ). Disease progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, as seen on CT scan, or the appearance of one or more new lesions on CT scan.

This trial can detect a difference in proportions alive without progression at 9 months from 50% in the erlotinib arm to 77% in the erlotinib plus hydroxychloroquine (HCQ) arm, using an alpha of 0.15 and power of 85%, using the two-sided Likelihood Ratio test. Progression is defined as at least a 20% increase in the size of existing lesions or the appearance of one or more new lesions.

To evaluate the safety of treatment with erlotinib with and without hydroxychloroquine (HCQ). All participants receiving study treatment were evaluated for safety. Parameters included laboratory tests, hematological abnormalities, physical exam findings and spontaneous reports of adverse events reported by participants. Toxicities were evaluated and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = fatal.

Response is assessed via spiral CT scan, done at baseline and after every 2 cycles of study treatment. Standard RECIST (Response Evaluation Criteria in Solid Tumors) was used. Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = at least a 30% decrease in the size of target lesions, as compared to baseline; Progressive Disease (PD) = at least at 20% increase in the size of target lesions, or the appearance of one or more new lesions; Stable Disease (SD) = neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

Response rate = CR + PR. Disease control rate = CR + PR + SD

Stanford University

Yale University

University of Maryland, College Park

Genentech, Inc.

Massachusetts General Hospital

Adverse events were collected via physical exam, eye exam and laboratory test. Additionally, participants were questioned at each study visit regarding other events not collected by the above methods.

Erlotinib: 150 mg taken orally once daily

Erlotinib: 150 mg taken orally once daily

Hydroxychloroquine: 1000 mg taken orally once daily after erlotinib

Erlotinib and Hydroxychloroquine

Total

Age, Continuous

Sex: Female, Male

Smoking History

Histology

Brain metastases

Prior chemotherapy

Maria Kempner

Median Progression Free Survival

Nine-month Progression-free Survival Rate

Diarrhea

Rash

Fatigue

Grade 3 Fatigue

Nausea

Anorexia

Taste changes

Grade 3 Taste changes

Alopecia

Weight loss

Ocular toxicity

Grade 4 or 5 events

Treatment Related Toxicity, > 10% Frequency, Any Grade

Complete Response

Partial Response

Stable Disease

Progressive Disease

Response Rate

Disease Control Rate

1 participant in each arm (2 participants total) did not have any scans done after baseline and therefore response could not be assessed.

Objective Tumor Response Rate Following Treatment With Erlotinib and With Erlotinib/HCQ.

Overall Survival of Patients Treated With Erlotinib and With Erlotinib/HCQ

Due to technical reasons, this assay was not ready and therefore circulating tumor cell analysis was not done.

Circulating Tumor Cell Quantification

Tumor tissue analysis was not performed for this correlative outcome.

EGFR Mutational Status

Only 2 participants were enrolled in this pilot companion study

Percent of Participants in Which FMISO-PET ([18F]-Fluoromisonidazole-positron Emission Tomography) is Able to Detect and Quantify Changes in Tumor Hypoxia After Erlotinib.

Overall Study

Digestive System Diseases

Carcinoma, Hepatocellular

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Chlorotrianisene

Subjects will receive HCQ plus standard of care TACE.

Gregory Nadolski, MD

Primary Phase I:To determine dose limiting toxicities and maximum tolerated dose (MTD) of the oral administration of hydroxychloroquine (HCQ) in conjunction with transarterial chemoembolization (TACE) in treating hepatocellular carcinoma (HCC). A conventional 3+3 design will be utilized. Primary Phase II: To evaluate the complete response rate in a cohort of patients treated at the MTD, A Simon's Optimal Two-stage design will be utilized.

Phase 1-2 Trial HCQ Plus TACE in Unresectable HCC

Phase I-II Clinical Trial of the Safety and Preliminary Efficacy of Hydroxychloroquine Combined With Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma

Adverse Events graded according to the Common Terminology Criteria of Adverse Events (CTCAE) version 4.0

Abramson Cancer Center at Penn Medicine

All adverse events occurring during the study period (up to 6 months after last dose of HCQ) were recorded. The clinical course of each event was followed until resolution, stabilization, or until it was determined that the study treatment or participation is not the cause. Serious adverse events that were still ongoing at the end of the study period must be followed up to determine the final outcome.

Subjects will receive HCQ plus standard of care TACE.

HCQ

TACE + HCQ

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Bilobar Hepatocellular Cancer (HCC)

Gregory Nadolski, MD, Principal Investigator

Number of Participants With Adverse Events

Subjects will receive Hydroxychloroquine (HCQ) plus standard of care Transarterial Chemoembolization (TACE).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients	NCT06389201	Nasopharyngeal ...	HCQ Placebo	20 Years - 70 Years	Affiliated Hospital of Nantong University
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients	NCT06389201	Nasopharyngeal ...	HCQ Placebo	20 Years - 70 Years	Affiliated Hospital of Nantong University
Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations	NCT00977470	Non-small Cell ...	Erlotinib Hydroxychloroqu...	18 Years -	Massachusetts General Hospital
Pretreatment With HCQ Before Radiotherapy and Chemotherapy in Advanced NPC Patients	NCT06389201	Nasopharyngeal ...	HCQ Placebo	20 Years - 70 Years	Affiliated Hospital of Nantong University
Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations	NCT00977470	Non-small Cell ...	Erlotinib Hydroxychloroqu...	18 Years -	Massachusetts General Hospital
Phase 1-2 Trial HCQ Plus TACE in Unresectable HCC	NCT02013778	Hepatocellular ...	HCQ	18 Years -	Abramson Cancer Center at Penn Medicine

Spots Global Cancer Trial Database for hcq

Every month we try and update this database with for hcq cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hcq

Every month we try and update this database with for hcq cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hcq cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.