Malignant Lymphoma of Extranodal and/or Solid Organ SitePhase 1NCT02575638
Safety Study of Camptothecin-20-O-Propionate Hydrate (CZ48)
A Phase 1 study testing CZ48 in people with Malignant Lymphoma of Extranodal and/or Solid Organ Site and Solid Tumor, run by Cao Pharmaceuticals Inc. at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Lymphoma of Extranodal and/or Solid Organ Site, Solid Tumor
- What is being tested?
- CZ48
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to 1 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Texas Health Science Center
San Antonio, Texas, 78229
CTRCReferral@uthscsa.edu
John Sarantopoulos, M.D.
About this study
Official title: 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)
Read the 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.
- Being tested
- CZ48
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CZ48Drug
Also called Camptothecin-20-O-Propionate hydrate
CZ48 is an analog of the topoisomerase I inhibitor Camptothecin (CPT). CPT is a natural extract from the tree Camptotheca acuminata
| Study group | Role | What they receive |
|---|---|---|
| Treatment population | Experimental | 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. Receives: Drug: CZ48 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Secondary outcomes (5)
Determine the Maximum Tolerated Dose (MTD)
Using the adverse event profile, the MTD will be established.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
Objective response
To assess responses by RECIST criteria when applicable
Measured: 3 months
Survival
To follow patients for survival.
Measured: 18 months (measured)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study startJul 2008
- Primary completion1 Oct 2019 (estimated)
- Study completion1 Feb 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Lymphoma of Extranodal and/or Solid Organ SiteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cao Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zhisong Cao, Ph. D., Principal investigator, Cao Pharmaeuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02575638
- Sponsor's protocol ID
- CZ48-01
- Status last verified
- Jul 2019
- First submitted
- 9 Oct 2015
- Last updated
- 23 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of Camptothecin-20-O-Propionate Hydrate (CZ48)
- ClinicalTrials.gov ID
- NCT02575638
- Acronym / sponsor ID
- CZ48-01
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 65 participants (estimated)
- Lead sponsor
- Cao Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Collaborators
- The University of Texas Health Science Center at San Antonio
- Study start
- Jul 2008
- Primary completion
- 1 Oct 2019 (estimated)
- Study completion
- 1 Feb 2020 (estimated)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment population | Experimental | Drug: CZ48The 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CZ48Also: Camptothecin-20-O-Propionate hydrateCZ48 is an analog of the topoisomerase I inhibitor Camptothecin (CPT). CPT is a natural extract from the tree Camptotheca acuminata | Drug | Treatment population |
Primary outcome
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.
5 secondary outcomes
Determine the Maximum Tolerated Dose (MTD)
Time frame: 4 weeks
Measure the Maximum Concentration (Cmax) level of drug in the blood plasma
Time frame: 4 weeks
Measure the Area Under the Curve (AUC) level of drug in the blood plasma
Time frame: 4 weeks
Objective response
Time frame: 3 months
Survival
Time frame: 18 months (measured)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2019.
- A study of 9-nitrocamptothecin (RFS-2000) in patients with advanced pancreatic cancerLink provided by the sponsor.
- Structure-Activity Relationship of Alkyl 9-Nitrocamptothecin EstersLink provided by the sponsor.
- Sulfuric Acid Catalyzed Preparation of Alkyl and Alkenyl Camptothecin Ester Derivatives and Antitumor Activity against Human Xenografts Grown in Nude MiceLink provided by the sponsor.
- Metabolic Difference of CZ48 in Human and Mouse Liver MicrosomesLink provided by the sponsor.
- Antitumor activity of new haloalkyl camptothecin esters against human cancer cell lines and human xenografts grown in nude miceLink provided by the sponsor.
- Enhanced Lactone Stability of CZ48 in Blood Correlates to its Lack of Toxicity in MiceLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhisong Cao, Ph. D. principal investigator
Cao Pharmaeuticals Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CZ48 in people with Malignant Lymphoma of Extranodal and/or Solid Organ Site and Solid Tumor, run by Cao Pharmaceuticals Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Doug Coil, BS (832-283-7705, dougc@caopharmaceuticals.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To describe the dose limiting toxicities as a measure of the adverse event profile (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2019.