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

Primary Purpose

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

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CZ48
Sponsored by
Cao Pharmaceuticals Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Malignant Lymphoma of Extranodal and/or Solid Organ Site

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Texas Health Science CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment population

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Determine the Maximum Tolerated Dose (MTD)
Using the adverse event profile, the MTD will be established.
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.
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.
Objective response
To assess responses by RECIST criteria when applicable
Survival
To follow patients for survival.

Full Information

First Posted
October 9, 2015
Last Updated
July 22, 2019
Sponsor
Cao Pharmaceuticals Inc.
Collaborators
The University of Texas Health Science Center at San Antonio
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1. Study Identification

Unique Protocol Identification Number
NCT02575638
Brief Title
Safety Study of Camptothecin-20-O-Propionate Hydrate (CZ48)
Official Title
Phase I Clinical Trial of Camptothecin-20-O-Propionate Hydrate (CZ48)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 2008 (undefined)
Primary Completion Date
October 1, 2019 (Anticipated)
Study Completion Date
February 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cao Pharmaceuticals Inc.
Collaborators
The University of Texas Health Science Center at San Antonio

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Lymphoma of Extranodal and/or Solid Organ Site, Solid Tumor

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment population
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CZ48
Other Intervention Name(s)
Camptothecin-20-O-Propionate hydrate
Intervention Description
CZ48 is an analog of the topoisomerase I inhibitor Camptothecin (CPT). CPT is a natural extract from the tree Camptotheca acuminata
Primary Outcome Measure Information:
Title
To describe the dose limiting toxicities as a measure of the adverse event profile
Description
To describe the dose limiting toxicities and adverse event profile of Camptothecin-20-O-Propionate hydrate (CZ48) administered orally for 1 course of treatment.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Determine the Maximum Tolerated Dose (MTD)
Description
Using the adverse event profile, the MTD will be established.
Time Frame
4 weeks
Title
Measure the Maximum Concentration (Cmax) level of drug in the blood plasma
Description
To measure the blood plasma levels of study drug at various time points to determine Cmax.
Time Frame
4 weeks
Title
Measure the Area Under the Curve (AUC) level of drug in the blood plasma
Description
To measure the blood plasma levels of study drug at various time points to determine AUC.
Time Frame
4 weeks
Title
Objective response
Description
To assess responses by RECIST criteria when applicable
Time Frame
3 months
Title
Survival
Description
To follow patients for survival.
Time Frame
18 months (measured)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Doug Coil, BS
Phone
832-283-7705
Email
dougc@caopharmaceuticals.com
First Name & Middle Initial & Last Name or Official Title & Degree
Zhisong Cao, Ph.D.
Phone
832-715-1039
Email
zhisongc@caopharmaceuticals.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhisong Cao, Ph. D.
Organizational Affiliation
Cao Pharmaeuticals Inc.
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Health Science Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CTRCReferral@uthscsa.edu
First Name & Middle Initial & Last Name & Degree
John Sarantopoulos, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/10200331
Description
A study of 9-nitrocamptothecin (RFS-2000) in patients with advanced pancreatic cancer
URL
https://www.infona.pl/resource/bwmeta1.element.elsevier-ded15d2d-7bd7-3a27-890b-e64a8d39932d
Description
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
URL
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=18169
Description
Sulfuric Acid Catalyzed Preparation of Alkyl and Alkenyl Camptothecin Ester Derivatives and Antitumor Activity against Human Xenografts Grown in Nude Mice
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382816/
Description
Metabolic Difference of CZ48 in Human and Mouse Liver Microsomes
URL
http://www.ingentaconnect.com/content/ben/acamc/2012/
Description
Antitumor activity of new haloalkyl camptothecin esters against human cancer cell lines and human xenografts grown in nude mice
URL
http://www.cspsCanada.org
Description
Enhanced Lactone Stability of CZ48 in Blood Correlates to its Lack of Toxicity in Mice

Learn more about this trial

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

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