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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02575638
• Other study ID #: CZ48-01
• Status: Recruiting
• Phase: Phase 1
• Start date: July 2008
• Est. completion date: February 1, 2020

Study information

• Verified date: July 2019
• Source: Cao Pharmaceuticals Inc.
• Contact: Doug Coil, BS
• Phone: 832-283-7705
• Email: dougc[@]caopharmaceuticals.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: February 1, 2020
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Malignant Lymphoma of Extranodal and/or Solid Organ Site
• Solid Tumor

Intervention

Drug:
• CZ48
CZ48 is an analog of the topoisomerase I inhibitor Camptothecin (CPT). CPT is a natural extract from the tree Camptotheca acuminata

Locations

Country	Name	City	State
United States	University of Texas Health Science Center	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Cao Pharmaceuticals Inc.	The University of Texas Health Science Center at San Antonio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Determine the Maximum Tolerated Dose (MTD)	Using the adverse event profile, the MTD will be established.	4 weeks
Secondary	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
Secondary	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
Secondary	Objective response	To assess responses by RECIST criteria when applicable	3 months
Secondary	Survival	To follow patients for survival.	18 months (measured)

External Links

•   A study of 9-nitrocamptothecin (RFS-2000) in patients with advanced pancreatic cancer
•   Alkyl esters of camptothecin and 9 - nitrocamptothecin: synthesis, in vitro pharmacokinetics, toxicity, and antitumor activity.
•   Antitumor activity of new haloalkyl camptothecin esters against human cancer cell lines and human xenografts grown in nude mice
•   Crystalline camptothecin-20(S)-O-propionate hydrate: A novel antitumor agent with strong activity against 19 human tumor xenografts.
•   Development and validation of a reverse-phase HPLC (high pressure liquid chromatography) with fluorescence detector method for simultaneous determination of CZ48 and its active metabolite camptothecin in mouse plasma
•   Enhanced Lactone Stability of CZ48 in Blood Correlates to its Lack of Toxicity in Mice
•   Metabolic Difference of CZ48 in Human and Mouse Liver Microsomes
•   Structure-Activity Relationship of Alkyl 9-Nitrocamptothecin Esters
•   Sulfuric Acid Catalyzed Preparation of Alkyl and Alkenyl Camptothecin Ester Derivatives and Antitumor Activity against Human Xenografts Grown in Nude Mice