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

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ClinicalTrials.gov Identifier: NCT02575638
Recruitment Status : Recruiting
First Posted : October 15, 2015
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
The University of Texas Health Science Center at San Antonio
Information provided by (Responsible Party):
Cao Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE October 9, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date July 23, 2019
Study Start Date  ICMJE July 2008
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2017)
  • Determine the Maximum Tolerated Dose (MTD) [ Time Frame: 4 weeks ]
    Using the adverse event profile, the MTD will be established.
  • 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.
  • 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.
  • Objective response [ Time Frame: 3 months ]
    To assess responses by RECIST criteria when applicable
  • Survival [ Time Frame: 18 months (measured) ]
    To follow patients for survival.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • Measure the highest amount of drug (Cmax) in the blood plasma level [ Time Frame: 4 weeks ]
    To measure the blood plasma levels of study drug at various time points during the first course of treatment to determine Cmax.
  • Objective response [ Time Frame: 3 months ]
    To assess responses by RECIST criteria when applicable
  • Survival [ Time Frame: 18 months (measured) ]
    To follow patients for survival.
  • Determine the Maximum Tolerated Dose (MTD) [ Time Frame: 4 weeks ]
    Using the adverse event profile, the MTD will be established.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Camptothecin-20-O-Propionate Hydrate (CZ48)
Official Title  ICMJE Phase I Clinical Trial of Camptothecin-20-O-Propionate Hydrate (CZ48)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Malignant Lymphoma of Extranodal and/or Solid Organ Site
  • Solid Tumor
Intervention  ICMJE Drug: CZ48
CZ48 is an analog of the topoisomerase I inhibitor Camptothecin (CPT). CPT is a natural extract from the tree Camptotheca acuminata
Other Name: Camptothecin-20-O-Propionate hydrate
Study Arms  ICMJE 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.
Intervention: Drug: CZ48
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 18, 2017)
65
Original Estimated Enrollment  ICMJE
 (submitted: October 12, 2015)
60
Estimated Study Completion Date  ICMJE February 1, 2020
Estimated Primary Completion Date October 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Doug Coil, BS 832-283-7705 dougc@caopharmaceuticals.com
Contact: Zhisong Cao, Ph.D. 832-715-1039 zhisongc@caopharmaceuticals.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02575638
Other Study ID Numbers  ICMJE CZ48-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Cao Pharmaceuticals Inc.
Study Sponsor  ICMJE Cao Pharmaceuticals Inc.
Collaborators  ICMJE The University of Texas Health Science Center at San Antonio
Investigators  ICMJE
Principal Investigator: Zhisong Cao, Ph. D. Cao Pharmaeuticals Inc.
PRS Account Cao Pharmaceuticals Inc.
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP