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

July 22, 2019 updated by: Cao Pharmaceuticals Inc.

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

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)

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

65

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University of Texas Health Science Center
        • Contact:
          • CTRCReferral@uthscsa.edu
        • Principal Investigator:
          • John Sarantopoulos, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment population
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
CZ48 is an analog of the topoisomerase I inhibitor Camptothecin (CPT). CPT is a natural extract from the tree Camptotheca acuminata
Other Names:
  • Camptothecin-20-O-Propionate hydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To describe the dose limiting toxicities as a measure of the adverse event profile
Time Frame: 4 weeks
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)
Time Frame: 4 weeks
Using the adverse event profile, the MTD will be established.
4 weeks
Measure the Maximum Concentration (Cmax) level of drug in the blood plasma
Time Frame: 4 weeks
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
Time Frame: 4 weeks
To measure the blood plasma levels of study drug at various time points to determine AUC.
4 weeks
Objective response
Time Frame: 3 months
To assess responses by RECIST criteria when applicable
3 months
Survival
Time Frame: 18 months (measured)
To follow patients for survival.
18 months (measured)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cao Pharmaceuticals Inc.

Collaborators

The University of Texas Health Science Center at San Antonio

Investigators

  • Principal Investigator: Zhisong Cao, Ph. D., Cao Pharmaeuticals Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2008

Primary Completion (Anticipated)

October 1, 2019

Study Completion (Anticipated)

February 1, 2020

Study Registration Dates

First Submitted

October 9, 2015

First Submitted That Met QC Criteria

October 12, 2015

First Posted (Estimate)

October 15, 2015

Study Record Updates

Last Update Posted (Actual)

July 23, 2019

Last Update Submitted That Met QC Criteria

July 22, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CZ48-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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