Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Liposome Entrapped Paclitaxel Easy to Use

The purpose of this study is to determine the highest dose of Liposome Entrapped Paclitaxel Easy to Use formulation (LEP-ETU) that can be safely administered by an intravenous infusion to patients with advanced cancer.

LEP-ETU is a new formulation of the anti-cancer agent paclitaxel for injection or Taxol (paclitaxel and Cremophor EL). Paclitaxel is a drug currently used for treating a broad range of cancers. Paclitaxel is thought to prevent cells from dividing and growing, resulting in cell death. This new formulation consists of paclitaxel associated with liposomes, which are microscopic membrane-like structures created from lipids (fats). It is believed that LEP-ETU will maintain or enhance the anti-tumor properties of paclitaxel, while offering advantages to the patient of a shorter infusion time, routine premedication not required, fewer side effects at similar doses, and possibly greater effectiveness, especially if higher doses can be delivered without an increase in side effects.

This study is designed to determine the following:

* The highest dose of LEP-ETU that can be given safely to patients.
* The pharmacokinetics of paclitaxel following intravenous infusion with LEP-ETU.
* Any anti-tumor effects of LEP-ETU.

Up to 8 dose levels will be studied. LEP-ETU will be given to patients by intravenous infusion over 90 minutes, once every 21 days, until their disease progresses or side effects occur requiring the treatments to end. Patients will be evaluated for safety and how well they tolerate the treatments.

Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) in Patients With Advanced Cancer

Phase I Study of Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) Formulation in Patients With Advanced Cancer

INSYS Therapeutics Inc

Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU)

Paclitaxel for injection (Taxol)

In this study, Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) is being compared to Taxol® to examine whether the paclitaxel in these 2 formulations undergoes similar processing by the body. Safety and tolerability of LEP-ETU and Taxol will also be assessed. In this study, each patient will receive one intravenous infusion of LEP-ETU or Taxol, followed 3 weeks later by an infusion of the other drug, at the same dose and infusion duration. Multiple blood samples will be taken for analysis before, during, and after both drug infusions. Upon completing these 2 Cycles of treatment, eligible patients may enroll in an extension study (LEP-ETU-102B) to continue treatment with LEP-ETU.

LEP-ETU is a liposomal formulation of paclitaxel, a widely used anti-cancer drug. This LEP-ETU formulation of paclitaxel is being developed to potentially reduce toxicities associated with Taxol, by eliminating the drug formulation component polyoxyethylated castor oil (Cremophor® EL). In LEP-ETU, paclitaxel is associated with liposomes, which are microscopic membrane-like structures created from lipids (fats). Thus, the LEP-ETU formulation could potentially have reduced toxicity, while maintaining or enhancing efficacy.

This Phase 1B, open-label, two-period crossover bioequivalence study is designed to compare the pharmacokinetics (PK) of LEP-ETU and Taxol in patients with advanced cancer. Patients are randomized to determine which drug is administered first. A single dose of LEP-ETU or Taxol (Cycle A) will be administered, followed 3 weeks later by a single dose of the other drug (Cycle B). Blood samples for PK analysis will be taken before, during, and after the infusion of each drug. Following successful completion of both Cycles in this study, patients may be eligible for additional cycles of treatment with LEP-ETU in the LEP-ETU-102B extension study.

Comparison of Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) and Taxol® Pharmacokinetics in Patients With Advanced Cancer

A Randomized Two-Period Crossover, Clinical Bioequivalence Study Comparing the Pharmacokinetics of Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) Formulation Versus Taxol® in Patients With Advanced Cancer

Digestive System Diseases

Colorectal Neoplasms

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Siblings (age \>40 and \<70) of individuals diagnosed with advanced neoplasm on screening colonoscopy. Advanced neoplasm is defined as adenomas≥10mm size, \>25% villous features, severe dysplasia or carcinoma-in-situ

Siblings (age \>40 and \<70) of individuals diagnosed with no polyp on screening colonoscopy who is age and sex matched to case.

Siew C Ng, PhD

BingYee Suen, BHSc

James Lau, MD

Justin C Wu, MD

James Y Lau, MD

Joseph J Sung, MD

To prospectively determine the prevalence of colorectal neoplasia in siblings of Hong Kong Chinese patients with advanced neoplasm compared with a sex and age-matched control population. To determine the molecular alteration profiles of colonic adenomas in siblings of patients with advanced neoplasm

The incidence of colorectal cancer (CRC) is rising rapidly in Hong Kong. It is the second commonest cancer in Hong Kong with more than 4000 new cases diagnosed in 2007, and it is also the second commonest cause of cancer death accounting for approximately 1,700 deaths per year. It has been estimated that 1 in 20 (5%) and 1 in 33 (3%) Hong Kong males and females, respectively, will develop CRC in their life time. (1) Data from the Hong Kong cancer registry showed that almost half of the cancer cases were stage III or IV disease at diagnosis which was associated with a worse prognosis(1), suggesting that earlier detection of CRC is important.

Genetic factors play an important role in the development of CRC. Approximately one fifth of CRC are associated with familial clustering(2), whilst hereditary syndromes including hereditary non- polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) account for approximately six percent of CRC cases (3;4)

Individuals with a family history of CRC have an increased risk of developing colonic neoplasm (cancer and adenoma). Meta-analyses of epidemiological studies showed that FDR of patients with CRC have an approximately two to three-fold increase risk of developing CRC compared with the general population (5-9). \[Table 1\]. The frequency of adenomas (12-69%) is also higher in relatives of patients with CRC although most of the earlier data have been derived from cohort studies (10-16). In the recent two case-control studies, the choice of the control population has been questionable (17;18) \[Table 2\]. Our own case-control study of screening colonoscopy in FDR with CRC, compared with FDR of patients with a normal colonoscopy ( published in abstract form) showed that the prevalence of colonic adenomas was significantly higher in cases compared with controls (25.3% versus 15.6%) (19).

Colorectal adenomas are precursors of CRC, and FDR of individuals with colonic adenomas also have an increased risk of CRC as well as colonic adenomas (20;21) The risk of developing colorectal neoplasia in FDR of patients with adenoma is likely be influenced by the characteristics of the adenoma in the index case. Colonic adenomas have a higher malignancy potential when they are greater than 10mm in size, and / or contains a villous component or severe dysplasia (22). In one study, relative risk of CRC for FDR was higher in relatives of patients with large adenomas (\>10mm) than in those with small adenomas (OR 2.1 and 1.2 respectively) (23). These findings have been reproduced in a recent study from France, which in addition showed that the risk was particularly high if the index case was younger than 60 years at diagnosis of a large adenoma, male or if they had a large adenoma in the left colon (24). In a separate study, relatives of patients with advanced neoplasm (OR1.62), but not those with small tubular adenomas (OR 1.26), have an increased risk of CRC (25).

Little is known about the prevalence of CRC and adenomas among siblings of individuals with advanced neoplasm in Hong Kong. Furthermore screening procedure for relatives of patients with high risk adenomas are not as well established as screening strategies for relatives of patients with CRC. This information is of important relevance in the formulation of an effective CRC screening strategy in Hong Kong (26). In a pilot screening project in 2001 among asymptomatic subjects of greater than 50 years old, the investigator have demonstrated an approximately 12% rate of advanced neoplasms using colonoscopy as a tool. Since 2008, asymptomatic subjects greater than 50 years old have been invited to undergo colonoscopy screening for CRC in PWH and AHNH hospital. To date about 1800 asymptomatic subjects have completed colonoscopy screening. This project provides the investigators with the opportunity to use an original design to determine the prevalence of colorectal neoplasia in siblings of patients with advanced neoplasm, compared with siblings of asymptomatic individuals who have had a negative screening colonoscopy during the same period of time.

The molecular pathways leading to tumour development in familial colorectal neoplasms are likely to be different from sporadic cases. Development of new molecular based methods for early detection, prevention or treatment relies heavily on the understanding of the differences between sporadic and familial neoplasms. Identification of genetic mutations can also improve genetic diagnosis and screening protocol of an at risk population.

The investigators hypothesize that siblings of patients with advanced neoplasm have an increased risk of both CRC and adenomas. The investigator aim to quantify this risk, and to identify other individual patient or neoplasm characteristics that may contribute to this increased risk. In addition, the investigator aim to determine molecular alteration profiles of colonic adenoma in siblings of patients with advanced neoplasm.

Investigator's preliminary data showed that the rate of advanced adenomas in controls (siblings of with normal colonoscopy) was 2%. Earlier studies have shown that the odds ratio of having colorectal neoplasms in close relatives of subjects with adenomas varies from 2.5 to 4.7. Using a conservative calculation, we assume that the prevalence of advanced adenomas in controls to be 3% and we estimate a 2.5-fold increased risk of advanced adenomas in siblings of individuals with advanced adenomas. Accordingly the recruitment of a minimum of 293 cases and 586 controls will be required to achieve 80% power to detect difference at a 5% significance level. For this project, investigators will aim to screen 300 siblings of patients with advanced adenomas and 600 matched controls.

A Prospective Study Into the Risk of Colorectal Neoplasms in Individuals With a Family History of Advanced Adenomas (Sibling AN Study)

With informed consents, experienced colonoscopists will perform colonoscopy under intravenous sedation During colonoscopic examination, endoscopists are instructed to remove all raised lesions. The size, location and morphologic feature of each raised lesion will be recorded. The size is measured again an open biopsy forceps (6mm apart). To avoid observer bias, colonoscopists and pathologists will be blinded from patient's details regarding family history of CRC or advanced neoplasms. Our group performed the first screening study among average risk Hong Kong Chinese in the locality (28)

Chinese University of Hong Kong

Professor of Medicine

LErafAON-ETU

The primary purpose of this study is to identify a dose of Liposome Entrapped c-raf Antisense Oligonucleotide Easy-to-Use (LErafAON-ETU) which maximizes potential benefits of the compound to patients with advanced cancer, without compromising their safety. This study will also assess the processing of LErafAON-ETU by the body over time. Patients will receive an intravenous infusion of LErafAON-ETU each week. Multiple blood samples will be taken for pharmacokinetic analysis during the first treatment; two samples will be taken during both the second and third treatments. Patients will be eligible to continue treatment until the occurrence of unacceptable toxicity or disease progression.

In LErafAON-ETU, antisense oligonucleotides specific to c-raf, are associated with liposomes, which are microscopic membrane-like structures created from lipids (fats). Raf-1 is a protein which plays a critical role in many aspects of cellular activation and growth. Therefore, it is thought to be an important factor that may support tumor development. LErafAON-ETU potentially limits the ability of a cell to produce the Raf-1 protein.

This Phase I, open-label, dose-escalation study is designed to determine the maximum tolerated dose of LErafAON-ETU in patients who have advanced cancer considered unresponsive to available, conventional modalities or treatments. LErafAON-ETU will be administered as an IV infusion once weekly for 3 consecutive weeks (a Treatment Cycle). A complete pharmacokinetic profile of raf-1 antisense oligonucleotide will be assessed in week 1 only; limited pharmacokinetic sampling will be done prior to and at the end of infusion in weeks 2 and 3 only. Tumor/disease evaluation will be performed upon completion of 6 infusions (2 Cycles). Dose escalation will not occur until the safety and tolerability at a given dose level has been confirmed for 1 Cycle.

Study to Determine the Maximum Tolerated Dose of LErafAON in Patients With Advanced Cancer

Phase I Study of an Easy-to-Use Intravenous Formulation of Liposome Entrapped C-raf Antisense Oligonucleotide (LErafAON-ETU) Administered on a Weekly Schedule in Patients With Advanced Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) in Patients With Advanced Cancer	NCT00080418	Neoplasm	Liposome Entrap...	18 Years -	INSYS Therapeutics Inc
Comparison of Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) and Taxol® Pharmacokinetics in Patients With Advanced Cancer	NCT00100139	Neoplasm	Liposome Entrap... Paclitaxel for ...	18 Years -	INSYS Therapeutics Inc
A Prospective Study Into the Risk of Colorectal Neoplasms in Individuals With a Family History of Advanced Adenomas (Sibling AN Study)	NCT01593098	Adenoma CRC		40 Years - 70 Years	Chinese University of Hong Kong
Comparison of Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) and Taxol® Pharmacokinetics in Patients With Advanced Cancer	NCT00100139	Neoplasm	Liposome Entrap... Paclitaxel for ...	18 Years -	INSYS Therapeutics Inc
Study to Determine the Maximum Tolerated Dose of LErafAON in Patients With Advanced Cancer	NCT00100672	Neoplasms	LErafAON-ETU	18 Years -	INSYS Therapeutics Inc
Study to Determine the Maximum Tolerated Dose of LErafAON in Patients With Advanced Cancer	NCT00100672	Neoplasms	LErafAON-ETU	18 Years -	INSYS Therapeutics Inc
Comparison of Liposome Entrapped Paclitaxel Easy to Use (LEP-ETU) and Taxol® Pharmacokinetics in Patients With Advanced Cancer	NCT00100139	Neoplasm	Liposome Entrap... Paclitaxel for ...	18 Years -	INSYS Therapeutics Inc

Spots Global Cancer Trial Database for advanced neoplasm