Safety Study of Camptothecin-20-O-Propionate Hydrate (CZ48)

Study Overview
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Brief Summary
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This is a single-arm, non-randomized feasibility and Phase I trial of 20(S) Camptothecin Propionate administered orally. CZ48 will be administered in successive cohorts of 1 patient per participating site until hints of toxicity (grade 2 or worse adverse events related to the drug) are observed. Then cohorts of 3+3 patients will be treated. CZ48 will be administered orally daily (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink up to one gallon of fluid daily if possible to flush the bladder to mitigate cystitis. Cystitis is an anticipated toxicity as CZ48 is a pro-drug of CPT (Camptothecin)

Detailed Description
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PRIMARY OBJECTIVE: • To describe the dose limiting toxicities and adverse event profile of Camptothecin-20-O-Propionate hydrate (CZ48) administered orally every day for 4 weeks (1 course). SECONDARYOBJECTIVE To determine the Maximum Tolerated Dose (MTD) of Camptothecin-20-O-Propionate hydrate (CZ48). To determine the blood plasma levels (PK study) of orally administered CZ48. To assess responses by Response Evaluation Criteria in Solid Tumors (RECIST) criteria when applicable. To follow patients for survival.

Official Title
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Phase I Clinical Trial of Camptothecin-20-O-Propionate Hydrate (CZ48)

Conditions
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Malignant Lymphoma of Extranodal and/or Solid Organ Site, Solid Tumor

Intervention / Treatment
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* Drug: CZ48


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a Performance Status (Zubrod) performance status of 0-1 Patients must sign an informed consent document Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of > 1,500 /mm3 and platelet count >100,000/mm3 along with an absence of a red blood cell transfusion in the two weeks prior to their participation in the trial Patients should have adequate hepatic function with a total bilirubin within normal range and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) < two times the upper limit of normal (ULN) for patients without liver metastasis and SGOT or SGPT < five times ULN for those with liver metastasis, and adequate renal function as defined by a serum creatinine within 1.5 times the upper limit of normal. Patients may receive no other concurrent anticancer treatments such as chemotherapy, hormone therapy (except for prostate cancer patients on luteinizing hormone-releasing hormone ((LHRH)) agonists), immunotherapy, biological agents, investigational agents, or radiation therapy during this trial, and should be off these treatments for at least 2 weeks, or until they have completely recovered from the side effects of these treatments, whichever is longest, except for persistent grade 1 neuropathy in patients who received prior platinum or taxanes. Exclusion Criteria: Patients with symptomatic brain metastases are excluded from this study. Patients with brain metastasis that have been treated, asymptomatic and off any steroid use are permitted for study Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception (contraceptive pill, or intrauterine device ((IUD)), or two mechanical barriers). Patients with severe uncontrolled medical problems are not eligible for this trial. Patients who have too much esterase as determined by a pre-screen dose, with a conversion rate yielding concentration of CPT > 100 ng/ml in vitro.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment population<br>The study drug, CZ48, is administered orally in capsule form t.i.d. Capsules in 30mg and 50mg of drug are available for dosing. This is a dose escalation study so dosage has not yet been determined. Study drug is take on day 1 - 5 and then no drug on day 6 and 7. This is repeated for 4 weeks, or one course. | Drug: CZ48<br>* CZ48 is an analog of the topoisomerase I inhibitor Camptothecin (CPT). CPT is a natural extract from the tree Camptotheca acuminata<br>* Other names: Camptothecin-20-O-Propionate hydrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe the dose limiting toxicities as a measure of the adverse event profile | To describe the dose limiting toxicities and adverse event profile of Camptothecin-20-O-Propionate hydrate (CZ48) administered orally for 1 course of treatment. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Maximum Tolerated Dose (MTD) | Using the adverse event profile, the MTD will be established. | 4 weeks | 
| Measure the Maximum Concentration (Cmax) level of drug in the blood plasma | To measure the blood plasma levels of study drug at various time points to determine Cmax. | 4 weeks | 
| Measure the Area Under the Curve (AUC) level of drug in the blood plasma | To measure the blood plasma levels of study drug at various time points to determine AUC. | 4 weeks | 
| Objective response | To assess responses by RECIST criteria when applicable | 3 months | 
| Survival | To follow patients for survival. | 18 months (measured) |