Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bortezomib

HIV Protease Inhibitors

Protease Inhibitors

Proteasome Inhibitors

bortezomib

radiation therapy

Carter Van Waes, M.D.

This study will test the safety and effects of the experimental drug PS-341 plus radiation therapy in patients with head and neck cancer. PS-341 can slow or halt the growth of cancer cells grown in culture or in mice. In addition, the drug appears to enhance the effectiveness of radiation treatment.

Patients 18 years of age and older with head and neck cancer that cannot be treated adequately with surgery and cannot be cured with standard radiation and chemotherapy may be eligible for this study. Patients whose cancer has spread to the brain may not participate.

Before treatment begins participants are evaluated with CT or MRI scans of the head, neck and chest area to determine the extent of the cancer; an electrocardiogram and blood tests; and a neurocardiovascular evaluation that includes measuring blood pressure in different body positions and involves injections of phenylephrine and nitroglycerine. Some patients may undergo a procedure in which a tube is inserted into the larynx (voice box), bronchi (breathing tubes) and esophagus (food tube) and tissue samples removed. This procedure is done under general anesthesia in the operating room.

Patients receive radiation treatments Monday through Friday and injections of PS-341 twice a week during the radiation therapy. After 3 weeks of treatment, PS-341 injections are stopped for 2 weeks. Some patients continue to receive radiation treatments during the 2-week break, and others do not, depending upon when they enter the trial. The total duration of radiation treatment varies from 6 to 8 weeks, depending on whether the patient received radiation in the region of the head and neck cancer before entering the study.

Patients have a blood sample drawn before and after each new PS-341 injection to measure the drug action in the blood and to see how strong and how long the effects on the blood last. They are seen in the clinic at least once a week for a history and physical examination. A blood sample is collected at each visit to look for toxic effects of PS-341. Near the end of treatment, the neurocardiovascular evaluation is repeated, and if the results are abnormal, it is repeated again 3 months after treatment is completed. X-rays or MRI scans are done 12 weeks after radiation therapy has ended and then every few months after that to determine the extent of disease. Patients whose tumor is accessible are asked to undergo a biopsy (removal of a small piece of tumor tissue) on the first and second day after receiving the first PS-341 dose to examine the effect of the drug on the tumor.

The PS-341 dose is increased in successive groups of at least 3 patients until the highest dose that can be given safely with radiation is reached. Patients who develop severe side effects from the drug temporarily stop taking it to allow the side effects to improve. If needed, the dose may be decreased. Radiation therapy may also be stopped temporarily in patients who develop severe effects on the mouth, throat or skin. Side effects may be treated with increased fluid (by mouth, stomach tube, or vein), anti-nausea or anti-diarrhea medications, pain medications and medications to boost red or white cell counts or platelets. The drug Florinef may be given to help regulate body fluids and blood pressure.

...

Background:

* The ubiquitin-proteasome pathway regulates the degradation of important regulatory proteins and transcription factors that control the cell cycle and cell death. Proteasome inhibition can lead to block of different phases of the cell cycle, and block expression of genes that prevent cell death induced by radiation or other cytotoxic therapeutic agents.
* In preclinical studies, proteasome inhibitor PS-341 has demonstrated cytotoxic, radiosensitizing, and anti-tumor activity against squamous cell carcinomas of the head and neck (SCCHN).

Objectives:

* The primary objective of this phase I dose escalation clinical study is to determine the maximum tolerated dose of PS-341 to be given concomitant with radiation in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
* Secondary objectives include detection of 20S proteasome inhibition, cell cycle block, apoptosis and inhibition of transcription factor NF-kappaB activation in tumor tissue biopsies following PS-341 and radiation.

Eligibility:

* Persistent or recurrent SCCHN,
* Eligible for local primary or re-irradiation,
* ECOG performance less than or equal to 2, life expectancy \> 3 months,
* Adequate organ function (PLT \> 100, 000/microL, neutrophils \> 1500/mciroL, serum creatinine \< 1.5 times the upper limits normal (ULN), serum bilirubin \< 1.5 times the ULN, serum transaminases \< 2.5 times the ULN)
* No systemic chemotherapy within the past 4 weeks and recovered from chemotherapy toxicity,
* \> 6 months since prior radiation.

Design:

* Phase I dose escalation, standard 3+3 statistical design, up to 51 subjects,
* PS-341 will be given in escalating doses of 0.6, 0.9 and 1.2 mg/m(2) in cohorts of 3 or more patients by IV bolus on M, Th (or T, F), and radiation will be given in 1.8 Gy fractions M-F to 60 Gy in previously radiated or 72Gy in previously unirradiated patients.
* Radiation and/or drug will be given in two courses split by a two week rest to allow recovery from combined modality therapy.

PS-341 and Radiation to Treat Advanced Cancer of the Head and Neck

A Phase I Study of Concomitant Therapy With Proteasome Inhibitor PS-341 and Radiation in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

National Cancer Institute (NCI)

Infections

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Warts

Condylomata Acuminata

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Genital Diseases

Urogenital Diseases

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Curcumin

Interferons

Interferon-gamma

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Enzyme Inhibitors

Participants received a dosage of 200mg capsules with active ingredient /Nanocurcumin per day after breakfast, for 8 weeks.

Participants received a dosage of 200mg capsules without Nanocurcumin per day after breakfast, for 8 weeks

Curcumin oral capsule in nano-sized particle.

Curcumin Oral Capsule

Trichloroacetic acid

Blood sample collection

Cotton swab for collecting sample from AGW lesions.

Cotton swab

Hernayati Hutabarat

The goal of this clinical trial is to demonstrate the adjuvant administration of oral nanocurcumin in 90% TCA therapy that increases the proportion of clinical improvement in patients with Anogenital Warts (AGW), mediated by NFĸB, IFN-γ, and FOXP3+Treg. Specific objectives of this clinical trial include:

* To prove that the oral administration of nanocurcumin decreases the levels of IFN-γ, FOXP3+Treg, and NFĸB in lesions of AGW patients, and
* To demonstrate that the reduction in IFN-γ, FOXP3+Treg, and NFĸB levels in lesions is associated with the proportion of clinical improvement in AGW patients undergoing TCA 90% therapy with adjuvant of oral nanocurcumin.

The main questions it aims to answer are:

* Does adjuvant oral nanocurcumin administration in 90% TCA therapy increase the proportion of clinical improvement in patients with AGW compared to controls (90% TCA therapy alone)?
* Is there a greater decrease in IFN-γ, FOXP3+Treg, and NFĸB levels in lesions of patients with AGW given adjuvant oral nanocurcumin compared to controls?
* Is the decrease in IFN-γ, FOXP3+TReg, and NFĸB levels in lesions of patients with AGW, with adjunctive oral nanocurcumin administration in 90% TCA therapy, associated with the degree of clinical improvement in patients with AGW?

Participants will be divided into 2 groups. The first one was given capsules without active ingredients/nanocurcumin (control group), and the second one was given capsules with nanocurcumin (experimental group), both group received a dosage of 200mg capsules per day after breakfast, for 8 weeks. The researchers conducted a comparison between those 2 groups to assess whether the adjuvant administration of oral nanocurcumin in 90% TCA therapy enhances the proportion of clinical improvement in patients with AGW.

The study is expected to enhance various aspects, including education, healthcare services, and research development aspects. This research aims to improve the understanding of the efficacy of oral nanocurcumin administration in patients with AGW and its implications on clinical aspects and its biomarkers (IFN-γ, Treg FOXP3+, and NF-kB levels) in AGW lesions. Therefore, it is anticipated to enhance the clinical improvement of the patients, potentially reducing the transmission rate of the disease. Furthermore, this study serves as a foundation for the development of future therapies for patients with AGW, opening avenues for further research endeavors, and exploring traditional medicine as a medical therapy with a robust evidence base.

Subjects were obtained from multiple centers in Indonesia, predominantly in Jakarta and nearby the area, such as, from the Dermatology \& Venereology outpatient clinic at Dr Cipto Mangunkusumo hospital, HIV and STI Clinics at Tambora Health Center (CINTTA Clinic), Penjaringan Health Center, Kalideres Health Center, Taman Sari Health Center, Cengkareng Health Center, and several foundations that provide care for HIV and STI patients. The acetic acid testing was conducted to confirm the diagnosis of AGW.

Lesions meeting the research criteria (a minimum of 3 lesions, and the diameter of at least one lesion is between 5 mm to under 50 mm) continued to be treated with 90% TCA solution. If participants had giant AGW lesions, they were referred to the Surgery outpatient clinic at Dr Cipto Mangunkusumo hospital for further management. Participants underwent 8 weekly visits.

Sample collection and drug administration protocol included: sample collection using wet cotton swabs swiped on the lesion for biomarkers (IFN-γ, FOXP3+TReg, and NFĸB) examination, as well as blood collection for HIV and CD4+ examination at week 1, 4, and 8, application of 90% TCA solution + nanocurcumin/control capsule administration at every visit for 8 weeks, along with control and clinical evaluation / side effect assessment. If lesions were no longer visible and the acetic acid test was negative by week 8, the lesions were considered healed and no further application of 90% TCA solution was conducted, but biomarkers examination continued. If lesions were still visible, application would continue until lesions were healed, with treatment continued at a center accessible to the patient. Participants who tested positive for HIV were referred to the HIV outpatient clinic for appropriate treatment.

Additional details related to the drug administration and sample collection protocol included:

* Participants were provided with information sheets on how to consume the medication and instructed on its usage and were required to fill out a Medication Diary every time they took the medication, experienced lapses, or developed any complaints.
* In case of non-compliance or lapses, patients were asked to write down and report to the contact number listed in the Diary.
* To reduce discomfort, the skin swabbing process was performed carefully and with sufficient time. Each patient was provided with Gentamicin cream to take home, in case of unwanted infections occurring at home, and were instructed to report to the researcher for further management.
* In case of side effects such as allergic reactions, nausea, vomiting, abdominal pain, or severe headaches, patients were instructed to report and discontinue medication consumption. They were provided with medication to alleviate symptoms and considered dropouts.
* Medications were provided for side effects including mild allergic reactions. For severe allergic reactions, participants were advised to immediately go to the nearest Emergency Department for management and the researcher would accompany them.
* The education provided to the participants included the following: scheduled follow-up visits every 7 days after therapy, postponement of sexual intercourse or the use protection (condoms), Counseling regarding the possibility of HIV and other STI transmission risks for themselves and their sexual partners, recommendation for pap smear examinations every 3 years for women aged 21 years and older, and Informing the sexual partners of the participants about the possibility of transmission even in the absence of visible lesions and encouraging them to undergo examinations.

The Effect of Oral Nanocurcumin as an Adjuvant Therapy for Anogenital Warts: Evaluation of Clinical Improvement, NFĸB, IFN-γ, and FOXP3+TReg From Lesions Tissue

The Effect of Oral Nanocurcumin as an Adjuvant Therapy for Anogenital Warts: Evaluation of Clinical Improvement, Nuclear Factor Kappa-Light-Chain-Enchancer of Activated B Cells, Interferon-γ, and FOXP3+ Regulatory T Cell From Lesions Tissue

The percentage reduction in the volume of AGW lesions in visit 8 compared to the initial volume.

* Decrease of IFN-γ level in lesions of AGW patients
* reduction in IFN-γ level in lesions is associated with the proportion of clinical improvement in AGW patients

* Decreases of FOXP3+Treg level in lesions of AGW patients
* reduction in FOXP3+Treg level in lesions is associated with the proportion of clinical improvement in AGW patients

* Decreases of NFĸB level in lesions of AGW patients
* reduction in NFĸB level in lesions is associated with the proportion of clinical improvement in AGW patients

Indonesia University

Dermatovenereologist, Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PS-341 and Radiation to Treat Advanced Cancer of the Head and Neck	NCT00011778	Squamous Cell C...	bortezomib radiation thera...	18 Years -	National Institutes of Health Clinical Center (CC)
The Effect of Oral Nanocurcumin as an Adjuvant Therapy for Anogenital Warts: Evaluation of Clinical Improvement, NFĸB, IFN-γ, and FOXP3+TReg From Lesions Tissue	NCT06281353	Anogenital Wart	Curcumin Oral C... Trichloroacetic... Blood sample co... Cotton swab	18 Years - 60 Years	Indonesia University

Spots Global Cancer Trial Database for nfkb

Every month we try and update this database with for nfkb 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 nfkb

Every month we try and update this database with for nfkb 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 nfkb 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.