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

NCT00947739 | Completed Phase 1 DMC

• 2 other identifiers: INST CZ48-01NCI-2011-02688
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 2

Brief Summary

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. 1.To describe the dose limiting toxicities and adverse event profile of Camptothecin-20-O-Propionate hydrate (CZ48) administered orally every day.
2. 2.To determine Phase II recommended dose of Camptothecin-20-O-Propionate hydrate (CZ48) administered orally every day.
3. 3.To perform a pharmacokinetic study of orally administered CZ48 in the plasma.
4. 4.To assess responses by RECIST criteria.
5. 5.To follow patients for survival.

Conditions

Advanced Solid Tumors; Lymphomas

Keywords

CZ; Stehlin; Lymphomas

Outcome Measures

Primary Outcomes (1)

• To describe the dose limiting toxicities, adverse event profile, and Phase II recommended dose of Camptothecin-20-O-Propionate hydrate (CZ48).

  3 weeks

Secondary Outcomes (1)

• To perform a pharmacokinetic study of orally administered CZ48 in the plasma. To assess responses by RECIST criteria and to follow patients for survival.

  3 weeks

Study Arms (15)

Cohort 1

EXPERIMENTAL

80 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48)PO, DAILY

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 2

EXPERIMENTAL

160 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 3

EXPERIMENTAL

320 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 4

EXPERIMENTAL

640 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 5a

EXPERIMENTAL

1280 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, DAILY

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 6

EXPERIMENTAL

2560 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 7

EXPERIMENTAL

18 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 8

EXPERIMENTAL

36 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 9

EXPERIMENTAL

72 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 10

EXPERIMENTAL

144 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 11

EXPERIMENTAL

288 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 12

EXPERIMENTAL

576 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 13

EXPERIMENTAL

750mg/m2 PO Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 14

EXPERIMENTAL

1000mg/m2 PO Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Cohort 5b

EXPERIMENTAL

1280 mg/m2 Camptothecin-20-O-Propionate Hydrate (CZ48) PO, TID

Drug: Camptothecin-20-O-Propionate Hydrate (CZ48)

Interventions

Camptothecin-20-O-Propionate Hydrate (CZ48) DRUG

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.

Also known as: CZ48

Cohort 1; Cohort 10; Cohort 11; Cohort 12; Cohort 13; Cohort 14; Cohort 2; Cohort 3; Cohort 4; Cohort 5a; Cohort 5b; Cohort 6; Cohort 7; Cohort 8; Cohort 9

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients, 18 years of age or older, with incurable advanced solid tumors or lymphomas are eligible.
• Patients must have a 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 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.
• 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.
• 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.

You may not qualify if:

• Patients with symptomatic brain metastases are excluded from this study.
• 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).
• Patients with severe uncontrolled medical problems are not eligible for this trial.
• 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.

Sponsors & Collaborators

• New Mexico Cancer Research Alliance: lead
• Christus Stehlin Foundation for Cancer Research: collaborator

Study Sites (2)

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

University of Texas Health Sciences Center

San Antonio, Texas, 78229, United States

Location

Related Links

• University of New Mexico Cancer Center
• University of Texas Health Sciences Center

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Monte Shaheen, M.D.

  University of New Mexico Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2009
• First Posted: July 28, 2009
• Study Start: September 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: March 1, 2014
• Last Updated: June 18, 2015

Record last verified: 2015-06

Locations

US (2)