Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Channel Blockers

Bone Density Conservation Agents

Ketoconazole

Carboxyamido-triazole

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Calcium

Calcium Channel Blockers

Calcium, Dietary

Patients receive oral carboxyamidotriazole (CAI) as a test dose on day 1. Patients receive oral ketoconazole on day 7, followed by CAI plus ketoconazole on day 8. CAI and ketoconazole are administered in combination on day 1 and days 3-28 of the first course. Ketoconazole is administered alone on day 2 of the first course. Subsequent courses begin at 28 day intervals in the absence of disease progression or unacceptable toxic effects. Cohorts of 3 patients are evaluated at each dose level prior to dose escalation. If one of three patients within a cohort experiences dose limiting toxicity (DLT), that dose level is expanded to incorporate six patients. If two or more patients experience DLT, the next lower dose is declared to be the maximum tolerated dose.

carboxyamidotriazole

chemotherapy

ketoconazole

Mark J. Ratain, MD

Phase I trial to study the effectiveness of carboxyamidotriazole and ketoconazole in treating patients with advanced cancers. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

OBJECTIVES:

I. Determine the maximum tolerated dose of carboxyamidotriazole (CAI) in combination with ketoconazole in patients with advanced malignancies.

II. Evaluate the toxic effects, safety, and efficacy of CAI in combination with ketoconazole.

III. Determine the modulatory effects of ketoconazole on the pharmacokinetic profile of CAI.

IV. Determine a pharmacodynamic model for CAI and ketoconazole with respect to potential gastrointestinal, hematologic, and neurotoxicities.

OUTLINE: This is a dose escalation study.

Patients receive oral carboxyamidotriazole (CAI) as a test dose on day 1. Patients receive oral ketoconazole on day 7, followed by CAI plus ketoconazole on day 8. CAI and ketoconazole are administered in combination on day 1 and days 3-28 of the first course. Ketoconazole is administered alone on day 2 of the first course. Subsequent courses begin at 28 day intervals in the absence of disease progression or unacceptable toxic effects. Cohorts of 3 patients are evaluated at each dose level prior to dose escalation. If one of three patients within a cohort experiences dose limiting toxicity (DLT), that dose level is expanded to incorporate six patients. If two or more patients experience DLT, the next lower dose is declared to be the maximum tolerated dose.

Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers

A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies

National Cancer Institute (NCI)

Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival.

Other: pharmacological study, radiation therapy

radiation therapy

pharmacological study

Tom Mikkelsen, MD

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Phase II trial to study the effectiveness of carboxyamidotriazole plus radiation therapy in treating patients who have newly diagnosed supratentorial glioblastoma multiforme.

PRIMARY OBJECTIVES:

I. To evaluate overall survival rate in patients administered CAI (carboxyamidotriazole) and radiation therapy to adults with newly diagnosed glioblastoma multiforme.

II. To determine the toxicity of CAI when combined with cranial irradiation. III. To estimate correlations between pharmacokinetic parameters, including steady state CAI concentration, with toxicity and/or drug activity in this patient population.

IV. To estimate duration of disease free progression with this treatment regime.

OUTLINE: This is a multicenter study.

Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study over 1.5 years.

Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

Phase II Clinical and Pharmacologic Study of Radiation Therapy and CAI (Carboxy-Amido Triazole) in Adults With Newly Diagnosed Glioblastoma Multiforme

estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death

patients who experienced a grade 3 or higher event considered at least possibly related to CAI

PK paramenters including steady state CAI concentrations with toxicity/or drug activity

CAI with RT

carboxyamidotriazole :

CAI : CAI 250 mg PO plus RT followed by 4wks CAI alone followed by 8wks CAI then MRI if stable or better continue until progression and then follow for survival

radiation therapy :

Arm 1

CAI With RT - Arm 1

Age, Customized

Sex: Female, Male

Race (NIH/OMB)

Performance Status 100

Performance Status 90

Performance Status 80

Performance Status 70

Performance Status 60

performance status is an attempt to quantify patients' general well-being and activities of daily life. The scale is in intervals of 10. 100 being normal and 0 dead. For ABTC studies you had to have a KPS of at least 60 (Requires occasional assistance, but is able to care for most of his personal needs) to be eligible for the study.

Karnofsky Performance Status

Stuart A Grossman

the study design is to detect 30% reduction in hazard of deaths with 78% power at one side alpha level of 0.10. Overall survial time was calculated from time of histological diagnosis until time of death from any event.

intent to treat pt population. time from histological diagnosis to death.

Overall Survival Rate

pts were treated for a median time of 2 months (23 days to 46 months). patients who experienced a grade 3 or higher event considered at least possibly related to CAI

Toxicity of CAI When Combined With RT

CAI With RT + Enzyme Inducing Anticonvulsants

CAI With RT Without Enzyme Inducing Anticonvulsants

Correlation Between PK CAI and Toxicity in This pt Population

Overall Study

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Mahrukh Hussain, MD

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

PURPOSE: Phase II trial to study the effectiveness of carboxyamidotriazole in treating patients with refractory or recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer.

OBJECTIVES:

* Determine the clinical outcome in patients with ovarian epithelial, fallopian tube, or primary peritoneal cancer treated with carboxyamidotriazole.

OUTLINE: Patients receive oral carboxyamidotriazole daily beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 19-40 patients will be accrued for this study within 2 years.

Carboxyamidotriazole in Treating Patients With Refractory or Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

A Phase II Trial of Orally Administered CAI for Patients With Persistent or Refractory Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Immunomodulating Agents

David Friedland, MD

RATIONALE: Carboxyamidotriazole may stop the growth of kidney cancer by stopping blood flow to the tumor.

PURPOSE: Phase II trial to study the effectiveness of carboxyamidotriazole in treating patients who have advanced kidney cancer that has not responded to biological therapy.

OBJECTIVES: I. Determine the disease free progression at 6 months in patients with locally recurrent or metastatic renal cell cancer (refractory to immunotherapy) treated with carboxyamidotriazole. II. Evaluate the progression free survival rate and response rate in these patients on this regimen. III. Evaluate the toxic effect of this regimen on these patients.

OUTLINE: Patients receive oral carboxyamidotriazole daily. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease may discontinue therapy after 6 courses. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and every 12 months thereafter until death.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 20 months.

Carboxyamidotriazole in Treating Patients With Advanced Kidney Cancer

Phase II Study of Carboxyamidotriazole (CAI, NSC #609974) in Patients With Advanced Renal Cell Carcinoma Refractory to Immunotherapy

Eastern Cooperative Oncology Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers	NCT00003249	Unspecified Adu...	carboxyamidotri... chemotherapy ketoconazole	18 Years -	National Cancer Institute (NCI)
Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM	NCT00004146	Adult Giant Cel... Adult Glioblast... Adult Gliosarco...	radiation thera... carboxyamidotri... pharmacological...	18 Years -	National Cancer Institute (NCI)
Carboxyamidotriazole in Treating Patients With Refractory or Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer	NCT00019461	Fallopian Tube ... Ovarian Cancer Primary Periton...	carboxyamidotri... chemotherapy	18 Years -	National Cancer Institute (NCI)
Carboxyamidotriazole in Treating Patients With Advanced Kidney Cancer	NCT00005045	Kidney Cancer	carboxyamidotri...	18 Years -	National Cancer Institute (NCI)
Carboxyamidotriazole in Treating Patients With Refractory or Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer	NCT00019461	Fallopian Tube ... Ovarian Cancer Primary Periton...	carboxyamidotri... chemotherapy	18 Years -	National Cancer Institute (NCI)
Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers	NCT00003249	Unspecified Adu...	carboxyamidotri... chemotherapy ketoconazole	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for carboxyamidotriazole