Phase I and Pharmacology Study of Camptothecin-20-O-Propionate Hydrate (CZ48) in Patients With Solid Tumors or Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Christus Stehlin Foundation for Cancer Research (actual sponsor)
Information provided by (Responsible Party):
New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier:
NCT00947739
First received: July 24, 2009
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

This is a phase I and pharmacology study of Camptothecin-20-O-Propionate Hydrate (CZ48) in Patients with Solid Tumors or Lymphoma.

OBJECTIVES

Primary:

  1. To describe the dose limiting toxicities and adverse event profile of Camptothecin-20-O-Propionate hydrate (CZ48) administered orally every day.
  2. To determine Phase II recommended dose of Camptothecin-20-O-Propionate hydrate (CZ48) administered orally every day.

    Secondary:

  3. To perform a pharmacokinetic study of orally administered CZ48 in the plasma.
  4. To assess responses by RECIST criteria.
  5. To follow patients for survival.

Condition Intervention Phase
Advanced Solid Tumors
Lymphomas
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I and Pharmacology Study of Camptothecin-20-O-Propionate Hydrate (CZ48) in Patients With Solid Tumors or Lymphoma

Resource links provided by NLM:


Further study details as provided by New Mexico Cancer Care Alliance:

Primary Outcome Measures:
  • To describe the dose limiting toxicities, adverse event profile, and Phase II recommended dose of Camptothecin-20-O-Propionate hydrate (CZ48). [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To perform a pharmacokinetic study of orally administered CZ48 in the plasma. To assess responses by RECIST criteria and to follow patients for survival. [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: September 2008
Study Completion Date: March 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
80 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48)PO, DAILY
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 2
160 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 3
320 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 4
640 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 5a
1280 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 6
2560 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 7
18 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 8
36 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 9
72 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 10
144 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 11
288 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 12
576 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 13
750mg/m2 PO Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 14
1000mg/m2 PO Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48
Experimental: Cohort 5b
1280 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID
Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)
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 cohort of 3+3 patients will be treated. CZ48 will be administered orally daily for 3 weeks followed by a 1 week rest. (1 course = 4 weeks). No pre-medications will be administered. Patients will be asked to drink 2 liters of fluid daily to flush the bladder.
Other Name: CZ48

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients, 18 years of age or older, with incurable advanced solid tumors or lymphomas are eligible.
  2. Patients must have a Zubrod performance status of 0-1.
  3. Patients must sign an informed consent document.
  4. Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of > 1,500 or cells/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.
  5. Patients should have adequate hepatic function with a total bilirubin within normal range and SGOT or SGPT < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine within the upper limit of normal.
  6. Patients may receive no other concurrent anticancer treatments such as chemotherapy, hormonotherapy (except for prostate cancer patients on 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:

  1. Patients with symptomatic brain metastases are excluded from this study.
  2. Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception (contraceptive pill, or IUD, or two mechanical barriers).
  3. Patients with severe uncontrolled medical problems are not eligible for this trial.
  4. Patients who have too much esterase activity in the blood, with a conversion rate yielding concentration of CPT > 20 ng/ml in vitro. Please see section 6.5 for sample collection, preparation and shipping. A validated analysis will be performed according to Sponsor SOP SFCR.PH.R.01.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00947739

Locations
United States, New Mexico
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States, 87131
United States, Texas
University of Texas Health Sciences Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
New Mexico Cancer Care Alliance
Christus Stehlin Foundation for Cancer Research (actual sponsor)
Investigators
Principal Investigator: Monte Shaheen, M.D. University of New Mexico Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: New Mexico Cancer Care Alliance
ClinicalTrials.gov Identifier: NCT00947739     History of Changes
Other Study ID Numbers: INST CZ48-01, NCI-2011-02688
Study First Received: July 24, 2009
Last Updated: April 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New Mexico Cancer Care Alliance:
CZ
Stehlin
Lymphomas

Additional relevant MeSH terms:
Lymphoma
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014