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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.

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)

Condition or disease Intervention/treatment Phase
Malignant Lymphoma of Extranodal and/or Solid Organ Site Solid Tumor Drug: CZ48 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Phase I Clinical Trial of Camptothecin-20-O-Propionate Hydrate (CZ48)
Study Start Date : July 2008
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : February 1, 2020

Resource links provided by the National Library of Medicine


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 Name: Camptothecin-20-O-Propionate hydrate




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Determine the Maximum Tolerated Dose (MTD) [ Time Frame: 4 weeks ]
    Using the adverse event profile, the MTD will be established.

  2. 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.

  3. 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. Objective response [ Time Frame: 3 months ]
    To assess responses by RECIST criteria when applicable

  5. Survival [ Time Frame: 18 months (measured) ]
    To follow patients for survival.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02575638


Contacts
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Contact: Doug Coil, BS 832-283-7705 dougc@caopharmaceuticals.com
Contact: Zhisong Cao, Ph.D. 832-715-1039 zhisongc@caopharmaceuticals.com

Locations
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United States, Texas
University of Texas Health Science Center Recruiting
San Antonio, Texas, United States, 78229
Contact: CTRCReferral@uthscsa.edu         
Principal Investigator: John Sarantopoulos, M.D.         
Sponsors and Collaborators
Cao Pharmaceuticals Inc.
The University of Texas Health Science Center at San Antonio
Investigators
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Principal Investigator: Zhisong Cao, Ph. D. Cao Pharmaeuticals Inc.
Additional Information:
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Responsible Party: Cao Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02575638    
Other Study ID Numbers: CZ48-01
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action