Symptoms and General Pathology

All Conditions

Neoplasms

Infections

Rare Diseases

Recurrence

Sarcoma

Sarcoma, Kaposi

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Communicable Diseases

Herpesviridae Infections

Virus Diseases

DNA Virus Infections

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Patients will receive Doxil at the standard dose of 20 mg/m2 IV for the 1st cycle. On the 2nd cycle of Doxil, the first patient will receive Doxil at 40% of standard dose or 8 mg/m2 (dose level 1) IV over one hr. 15 mn after the 2nd and subsequent cycles of Doxil, PSC 833 will be given at 2 mg/kg for 2 hrs. Simultaneously, a 72 hour CIVI of PSC 833 will be started with the loading dose. If no DLT occurs, then a double dose escalation of Doxil (dose levels 3, 5, 7 ) will be given to the same patient in the subsequent cycles until DLT occurs. On the 2nd cycle, Doxil will be given at the next dose level above the starting dose tolerated by the first patient. If no DLT occurs, a double dose escalation will also be done for the subsequent cycles (dose levels 5, 7, 9). The single-patient-cohort will terminate when a patient experiences DLT or when two episodes of grade 2 toxicity occur. At that point patients will be enrolled into cohorts of 3 patients to determine the MTD.

pegylated liposomal doxorubicin hydrochloride

PSC 833

Paula M. Fracasso, MD, PhD

The rationale for conducting this study lies in the premise that if indeed the reason for a limited response of Kaposi's sarcoma lesions and other advanced malignancies to chemotherapy is attributable to a high expression of P-glycoprotein, then, by inhibiting this pump, tumor kill would be enhanced and response rates as well as duration of responses would also increase. Doxil is chosen since recent studies have shown that it is superior to combination chemotherapy with ABV or BV. Doxil is also known to be active in other malignancies such as breast and ovarian cancer (34,35). PSC 833 is chosen since it has been found to reverse P-gp in vitro and in vivo, is non-immunosuppressive, and has been shown in recent Phase 1 studies to be well tolerated.

There are yet no human studies reported on Doxil pharmacokinetics when combined with MDR modulators. Preclinical data shows that pharmacokinetics of Doxil, unlike free doxorubicin, is minimally affected by the addition of PSC 833 (36). Enhanced tumor toxicity was observed when PSC 833 was combined with Doxil. Since doxorubicin, the active agent in Doxil, is metabolized by the same cytochrome P450, interactions between these 2 agents may have very significant clinical implications. The purpose of this study is to assess the toxicity and determine the maximum tolerated dose of Doxil when combined with PSC 833 in the treatment of AIDS-KS and other advanced malignancies.

Liposomal Doxorubicin and PSC 833 in Treating Patients With AIDS-Related Kaposi's Sarcoma or Other Advanced Cancers

Phase I Study on Doxil and SDZ PSC 833 in the Treatment of AIDS-Associated Kaposi's Sarcoma and Other Advanced Malignancies

Each cycle is 2 weeks long and can continue until disease progression, toxicity, or patient decision

National Cancer Institute (NCI)

Washington University School of Medicine

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Immune System Diseases

Carcinoma

Breast Neoplasms

Carcinoma, Renal Cell

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Lymphoma

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urogenital Neoplasms

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Lymphosarcoma

Antirheumatic Agents

Dermatologic Agents

Paclitaxel

Albumin-Bound Paclitaxel

Cyclosporine

Cyclosporins

polysaccharide-K

Tubulin Modulators

Antimitotic Agents

paclitaxel

This is a dosage escalation study to estimate the maximum tolerated dose of drug resistance inhibitor PSC 833 given in combination with paclitaxel. Groups of 3 to 6 patients receive continuous-infusion paclitaxel for 5 days and oral PSC 833 for 6-7 days, following paclitaxel on the first course, then beginning 3 days prior to paclitaxel on subsequent courses.

Stable and responding patients are re-treated every 21 days, with paclitaxel dose adjusted to maintain an absolute neutrophil count less than 500 for no more than 4 days.

The clinical study entitled "A Phase I Study of Infusional Paclitaxel with the P-glycoprotein Antagonist PSC 833" seeks to determine the maximum tolerated dose for the proposed P-glycoprotein antagonist, PSC 833, in combination with paclitaxel. PSC 833 is a cyclosporine analogue which is purportedly non-nephrotoxic and non-immunosuppressive. It has been shown in in vitro studies to enhance chemosensitivity as well as cyclosporine and to be far better at increasing intracellular drug accumulation than the concentrations of verapamil which are clinically achievable. The purpose of this study is to define the maximum tolerated dose in combination with paclitaxel, and to determine how the drug affects the pharmacokinetics of paclitaxel. PSC 833 will most likely reduce the clearance of paclitaxel as reported for the parent compound, cyclosporine. This effect will increase the area under the curve (AUC) of paclitaxel, may increase toxicity, and requires that the escalation scheme for PSC 833 be a conservative one. The first cycle of paclitaxel will be given in the absence of PSC 833. Subsequently, 7 days of PSC 833 will be given alone to allow monitoring of pharmacokinetics and adverse effects of PSC 833 alone. In the second cycle, both agents will be combined. Escalation of the PSC 833 will continue until a target concentration is reached, or until the maximum tolerated dose is reached. Clinical responses will be monitored in order to provide the best possible medical care to our patients.

A Phase I Study of Infusional Paclitaxel With the P-Glycoprotein Antagonist PSC 833

Neoplasm Metastasis

Neoplastic Processes

Renal Cell Carcinoma

Vinblastine

vinblastine

Bolus PSC 833 is administered on Day 1 simultaneously with initiation of 24 hour continuous infusion of PSC 833, followed by another continuous infusion lasting an additional 6 days. To ensure the safety of a 7 day infusion of PSC 833, one patient is treated for 5 days and a second for 6 days, before the first cohort is enrolled.

Vinblastine is administered in escalating doses on days 2-5. At least 3 patients are entered at each dose level. The MTD will be defined as the dose immediately below that at which 2 patients experience dose limiting toxicity.

Treatment continues every 28 days.

The Phase I clinical trial of the combination of 120-hour continuous intravenous infusion of vinblastine with oral PSC 833 has shown activity in patients with advanced malignancies, particularly renal cell cancer. The MTD of vinblastine in combination with the oral drink solution of PSC 833 was determined to be 0.9 mg/m2/day for five days and 12.5 mg/kg po q 12 hours for eight days, respectively. For the soft gel capsule formulation, the MTD was determined to be 0.6 mg/m2/day vinblastine for five days and 4 mg/kg po q 6 hours PSC 833 for eight days. Ataxia was the dose limiting toxicity. Of the 46 patients, two complete remissions and one partial remission were seen among 29 patients with renal cell carcinoma.

In this Phase I study, patients with advanced renal carcinoma will be treated with escalating doses of vinblastine given as a 72 hour infusion, starting at approximately 40% of the total standard dose. A shorter infusion schedule of vinblastine was chosen since there is evidence in other cytotoxic combinations that PSC 833 increases the AUC and decreases the plasma clearance of chemotherapeutic agents by approximately twofold. Cytochrome P 450 3A or CYP3A, which is the major cytochrome enzyme in the metabolism of vinblastine and PSC 833, will be measured during the first and fourth cycle through an in vivo test using a single intravenous dose of midazolam, a short-acting benzodiazepine. Vinblastine and PSC 833 pharmacokinetics will be performed at the same time. For patients with accessible lesions, tumor biopsy will be requested.

A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer

The clinical study entitled "A Phase I Study of Infusional Chemotherapy with the P-glycoprotein Antagonist PSC 833" seeks to determine the maximum tolerated dose for a proposed P-glycoprotein antagonist, PSC 833. PSC 833 is a cyclosporine analogue which is purportedly non-nephrotoxic and non-immunosuppressive. It has been shown in in-vitro studies to enhance chemosensitivity as well as cyclosporine and to be far better at increasing intracellular drug accumulation than the concentrations of verapamil which are clinically achievable. The purpose of this study is to define the maximum tolerated dose in combination with vinblastine, and to determine how the drug affects the pharmacokinetics of vinblastine. PSC 833 will most likely reduce the clearance of vinblastine, as reported for the parent compound, cyclosporine. This effect will increase the area under the curve (AUC) of vinblastine, may increase toxicity, and requires that the escalation scheme for PSC 833 be a conservative one. Initially, a 120 hour infusion of vinblastine will be given alone. Then 8 days of PSC 833 will follow to allow monitoring of adverse effects of PSC 833 alone. This first cycle of vinblastine will be given in the absence of PSC 833; in second and subsequent cycles both agents will be combined. Escalation of the PSC 833 will continue until a target concentration is reached, or until the maximum tolerated dose is reached. Clinical responses will be monitored in order to provide the best possible medical care to our patients.

The clinical study entitled "A Phase I Study of Infusional Chemotherapy with the P-glycoprotein Antagonist PSC 833" seeks to determine the maximum tolerated dose for a proposed P-glycoprotein antagonist, PSC 833. PSC 833 is a cyclosporine analogue which is purportedly non-nephrotoxic and non-immunosuppressive. It has been shown in in vitro studies to enhance chemosensitivity as well as cyclosporine and to be far better at increasing intracellular drug accumulation than the concentrations of verapamil which are clinically achievable. The purpose of this study is to define the maximum tolerated dose in combination with vinblastine, and to determine how the drug affects the pharmacokinetics of vinblastine. PSC 833 will most likely reduce the clearance of vinblastine, as reported for the parent compound, cyclosporine. This effect will increase the area under the curve (AUC) of vinblastine, may increase toxicity, and requires that the escalation scheme for PSC 833 be a conservative one. Initially, a 120 hour infusion of vinblastine will be given alone. Then 8 days of PSC 833 will follow to allow monitoring of adverse effects of PSC 833 alone. This first cycle of vinblastine will be given in the absence of PSC 833; in second and subsequent cycles both agents will be combined. Escalation of the PSC 833 will continue until a target concentration is reached, or until the maximum tolerated dose is reached. Clinical responses will be monitored in order to provide the best possible medical care to our patients.

A Phase I Study of Infusional Chemotherapy With the P-Glycoprotein Antagonist PSC 833

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Liposomal Doxorubicin and PSC 833 in Treating Patients With AIDS-Related Kaposi's Sarcoma or Other Advanced Cancers	NCT00003207	Sarcoma Unspecified Adu...	pegylated lipos... PSC 833	18 Years -	Washington University School of Medicine
A Phase I Study of Infusional Paclitaxel With the P-Glycoprotein Antagonist PSC 833	NCT00001383	Breast Cancer Cancer Carcinoma, Rena... Lymphoma Ovarian Cancer	PSC 833 paclitaxel	-	National Institutes of Health Clinical Center (CC)
A Phase I Study of Continuous Intravenous Infusion of PSC 833 and Vinblastine in Patients With Metastatic Renal Cancer	NCT00001570	Kidney Neoplasm... Neoplasm Metast...	PSC 833 vinblastine	-	National Institutes of Health Clinical Center (CC)
A Phase I Study of Infusional Paclitaxel With the P-Glycoprotein Antagonist PSC 833	NCT00001383	Breast Cancer Cancer Carcinoma, Rena... Lymphoma Ovarian Cancer	PSC 833 paclitaxel	-	National Institutes of Health Clinical Center (CC)
A Phase I Study of Infusional Chemotherapy With the P-Glycoprotein Antagonist PSC 833	NCT00001302	Breast Cancer Kidney Neoplasm Lymphoma Neoplasm Metast... Ovarian Cancer	PSC 833	-	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for psc 833

Every month we try and update this database with for psc 833 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 psc 833

Every month we try and update this database with for psc 833 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 psc 833 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.