This is a dose escalation study. Patients receive oral COL-3 once daily. Treatment continues in the absence of disease progression and unacceptable toxic effects. Cohorts of 3-6 patients each receive escalating doses of COL-3. Dose escalation to the next level occurs after 3 patients have completed 28 days of treatment without dose limiting toxicity (DLT). Dose escalation continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience DLT.

incyclinide

Eric K. Rowinsky, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of COL-3 in treating patients who have advanced solid tumors.

OBJECTIVES: I. Define the maximum tolerated dose of COL-3 in patients with advanced solid tumors. II. Identify the dose limiting toxicity and safety profile of COL-3 in these patients. III. Define the pharmacokinetics and pharmacodynamics of COL-3 in these patients. IV. Observe any evidence of antitumor activity through standard response criteria or biologic surrogate markers.

OUTLINE: This is a dose escalation study. Patients receive oral COL-3 once daily. Treatment continues in the absence of disease progression and unacceptable toxic effects. Cohorts of 3-6 patients each receive escalating doses of COL-3. Dose escalation to the next level occurs after 3 patients have completed 28 days of treatment without dose limiting toxicity (DLT). Dose escalation continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience DLT.

PROJECTED ACCRUAL: Up to 30 patients will be accrued within 1 year for this study.

Chemotherapy in Treating Patients With Advanced Solid Tumors

A Phase I, Pharmacologic and Biologic Study of Col-3 (NSC683551) Administered on a 28-Day Oral Dosing Schedule in Patients With Advanced Solid Tumors

National Cancer Institute (NCI)

The University of Texas Health Science Center at San Antonio

Infections

All Conditions

Symptoms and General Pathology

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Communicable Diseases

Sarcoma

Acquired Immunodeficiency Syndrome

HIV Infections

Sarcoma, Kaposi

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

Patients receive low-dose oral COL-3 once daily.

Treatment on both arms continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed.

Patients receive high-dose oral COL-3 once daily.

Treatment on both arms continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed.

laboratory biomarker analysis

Bruce Dezube

COL-3 may stop the growth of cancer by stopping blood flow to the tumor. Randomized phase II trial to compare the effectiveness of two different regimens of COL-3 in treating patients who have HIV-related Kaposi's sarcoma.

PRIMARY OBJECTIVES:

I. To evaluate the tumor response rate and response duration of treatment with Col-3 at two different dose levels- 50 mg/day and 100 mg/day in subjects with HIV related KS.

II. To evaluate the biologic activity of Col-3 by measuring percent apoptotic cells on tumor biopsies pre- and post-treatment.

III. To evaluate the effect of Col-3 on serum levels of MMP-2 and MMP-9.

SECONDARY OBJECTIVES:

I. To determine the safety and toxicity of Col-3 at two different dose levels in HIV related KS.

II. To evaluate the effect of Col-3 on overall quality of life. III. To evaluate the relationship between clinical response and quantitative measures of KSHV/HHV-8 and HIV viral load.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive low-dose oral COL-3 once daily.

Arm II: Patients receive high-dose oral COL-3 once daily.

Treatment on both arms continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed.

Patients are followed for at least 1 month.

PROJECTED ACCRUAL: A total of 70 patients (35 per treatment arm) will be accrued for this study within 1.75 years.

A Phase II Trial of COL-3 in Patients With HIV Related Kaposi's Sarcoma

Binomial proportions and their 95% confidence intervals will be used to estimate the overall response rate for each treatment group.

The Kaplan-Meier Method will be used to estimate the distribution of response duration for each treatment group.

Will be tabulated to evaluate tolerance of each dose level in the treatment of AIDS-related Kaposi's Sarcoma.

The Kaplan-Meier Method will be used to estimate the distribution of time to response for each treatment group.

Individual composite scores will be constructed. Repeated measures and an analysis of variance will be performed on the composite scores to evaluate changes with time. Mixed models will be applied to the analysis of the composite score.

These measures will be tested to determine if they are normally distributed. If the data are non-normal, the data will be transformed for analysis purposes. The logistic regression model will be used to assess the relationship between qualification of baseline levels of KSHV/HHV-8, HIV viral load and response. The proportional hazards model will be used to evaluate the relationship between the qualification of baseline KSHV/HHV8 and HIV viral load and time to progression, and response duration.

Nervous System Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Astrocytoma

Oligodendroglioma

Central Nervous System Neoplasms

Nervous System Neoplasms

Gliosarcoma

Brain Tumor, Adult

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Pamela Z. New, MD

RATIONALE: COL-3 may stop the growth of brain tumors by stopping blood flow to the tumor.

PURPOSE: Phase I/II trial to study the effectiveness of COL-3 in treating patients who have progressive or recurrent brain tumors following radiation therapy or chemotherapy.

OBJECTIVES:

* Determine the maximum tolerated dose, dose limiting toxicity, and safety profile of oral COL-3 alone or when combined with anticonvulsants known to be metabolized by CYP450 in patients with progressive or recurrent high grade anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme.
* Define the pharmacokinetics and pharmacodynamics of COL-3 on this schedule and determine the effects of hepatic enzyme inducing drugs, such as anticonvulsants, on the pharmacokinetics.
* Determine the response rate, disease free survival, and survival in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study of COL-3. Patients are stratified by anticonvulsant (anticonvulsants that cause induction of CYP450 vs anticonvulsants that cause modest or no induction of CYP450 or no anticonvulsant).

* Phase I: Patients receive oral COL-3 daily. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of COL-3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.

* Phase II: Patients receive oral COL-3 daily at the MTD from the phase I portion of this study.

Patients are followed every 2 months until death.

PROJECTED ACCRUAL: A total of 15-18 patients will be accrued for phase I of the study and a total of 35 patients will be accrued for phase II of the study at a rate of 3 patients per month.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemotherapy in Treating Patients With Advanced Solid Tumors	NCT00003721	Unspecified Adu...	incyclinide	18 Years -	The University of Texas Health Science Center at San Antonio
A Phase II Trial of COL-3 in Patients With HIV Related Kaposi's Sarcoma	NCT00020683	AIDS-related Ka... HIV Infection	incyclinide incyclinide laboratory biom...	18 Years -	National Cancer Institute (NCI)
COL-3 in Treating Patients With Progressive or Recurrent Brain Tumors	NCT00004147	Brain and Centr...	incyclinide	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for incyclinide

Every month we try and update this database with for incyclinide cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for incyclinide

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