Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Phase I Study of Zalypsis (PM00104) in Subjects With Advanced Malignant Solid Tumors or Lymphoma

This study has been terminated.
(Considered not necessary to continue with this trial; recommended dose was reached in other phase I trials)
Sponsor:
Information provided by:
PharmaMar
ClinicalTrials.gov Identifier:
NCT00359294
First received: August 1, 2006
Last updated: April 20, 2009
Last verified: October 2008
  Purpose

Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma.


Condition Intervention Phase
Solid Tumors
Lymphoma
Drug: Zalypsis (PM00104)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Multicenter, Open-Label, Dose-Escalating Clinical and Pharmacokinetic Study of PM00104 Administered Intravenously Over 1 Hour Daily for 5 Days, Every 3 Weeks, to Subjects With Advanced Malignant Solid Tumors or Lymphoma.

Resource links provided by NLM:


Further study details as provided by PharmaMar:

Primary Outcome Measures:
  • To determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104 [ Time Frame: Along the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the preliminary pharmacokinetics of PM00104. To evaluate the relationship between pharmacokinetics/pharmacodynamics. To evaluate the preliminary antitumor activity of PM00104. [ Time Frame: Along the study ] [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: May 2006
Estimated Study Completion Date: September 2008
Estimated Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Zalypsis (PM00104)
Intravenously over 1 hour daily for 5 days, every 3 weeks.

Detailed Description:

Phase I trial, dose escalating, prospective, open-label, non-randomized, multicenter study. The purpose is to determine the safety, tolerability, dose limiting toxicity (DLT) and recommended dose (RD) of PM00104, administered intravenously over 1 hour daily for 5 days every 3 weeks (this is considered as 1 cycle) to subjects with advanced malignant solid tumors or lymphoma. Secondary objectives are to determine the preliminary pharmacokinetics of PM00104, to evaluate the relationship between pharmacokinetics/pharmacodynamics and to evaluate the preliminary antitumor activity of PM00104. Dose-escalation guidelines will follow an accelerated phase I design for conventional cytotoxic agents in order to minimize the number of subjects treated at the subtoxic dose levels. The trial will be conducted in compliance with the protocol, GCP and applicable regulatory requirements.

  Eligibility

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

Inclusion Criteria:

  1. Voluntary written informed consent of the subject obtained before any study-specific procedure.
  2. Histologically or cytologically confirmed malignant solid tumor or lymphoma.
  3. Subjects with malignancies that are not otherwise curable or for which no effective standard therapy exists.
  4. Age ≥ 18 years.
  5. Subject with measurable or non-measurable disease using the RECIST criteria
  6. Recovery from any drug-related adverse event related to previous treatment, excluding alopecia and NCI-CTCAE grade < 2 peripheral neuropathy.
  7. Laboratory values within 7 days prior to first infusion:

    • Platelet count ≥ 100 x109/L, hemoglobin ≥ 9 g/dL and absolute neutrophil count (ANC) ≥ 1.5 x109/L.
    • Alkaline phosphatase ≤ 2.5 x the upper limit of normal (ULN) (≤ 5 x ULN in case of extensive bone metastases)
    • Aspartate aminotransferase (AST): ≤ 2.5 x ULN
    • Alanine aminotransferase (ALT): ≤ 2.5 x ULN
    • Total bilirubin: ≤ 1.5 ULN, unless due to Gilbert's syndrome.
    • Creatinine: ≤ ULN, or calculated creatinine clearance: ≥ 60 mL/min (calculated from the Cockcroft-Gault formula; see Appendix III).
    • Albumin: ≥ 2.5 g/dL.
    • Partial tromboplastin within normal limits for the institution
    • INR within normal limits for the institution (unless due to oral anticoagulation)
  8. Performance status (ECOG) ≤ 1
  9. Life expectancy ≥ 3 months.
  10. Left ventricular ejection fraction (LVEF) within normal limits for the institution (LVEF of at least 50%).
  11. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both men and women must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include complete abstinence, IUD, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).

Exclusion Criteria:

  1. Prior therapy with PM00104
  2. Pregnant or lactating women.
  3. Less than 4 weeks from radiation therapy (8 weeks in case of extensive prior radiotherapy) or last dose of hormonal therapy, biological therapy or chemotherapy (6 weeks in case of nitrosourea, mitomycin C).
  4. Prior high dose chemotherapy that needed bone marrow transplant support.
  5. Subjects with untreated or uncontrolled brain or meningeal metastases.
  6. Other relevant diseases or adverse clinical conditions:

    • Increased cardiac risk as defined by:

      • History or presence of unstable angina.
      • History or presence of myocardial infarction.
      • Congestive heart failure.
      • Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment.
      • Abnormal ECG (i.e., patients with the following are excluded: QT prolongation-QTc > 480 msec-, signs of cardiac enlargement or hypertrophy, bundle branch block, partial bundle branch blocks, signs of ischemia or necrosis, Wolff-Parkinson-White patterns).
      • History or presence of valvular heart disease.
      • Uncontrolled arterial hypertension despite optimal medical therapy.
      • Previous mediastinal radiotherapy.
      • Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m2
    • History of significant neurological or psychiatric disorders.
    • Active infection.
    • Significant non-neoplastic liver disease (e.g., cirrhosis, chronic active hepatitis).
    • Significant non-neoplastic renal disease.
    • Immunocompromised subjects, including subjects known to be infected by human immunodeficiency virus (HIV).
    • Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism or hyperthyroidism, adrenal disorder) requiring relevant changes in medication within the last month or hospital admission within the last 3 months.
    • Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with the subject's participation in this study.
  7. Limitation of the subject's ability to comply with the treatment or to follow-up at a participating center. Subjects registered on this trial must be treated and followed at a participating center.
  8. Treatment with any investigational product in the 30 days period prior to the first infusion.
  9. Known hypersensitivity to any of the components of the drug product, including sucrose or potassium phosphate.
  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: NCT00359294

Locations
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
PharmaMar
Investigators
Principal Investigator: Nancy Lewis, MD Fox Chase Cancer Center
  More Information

No publications provided

Responsible Party: PharmaMar USA Inc
ClinicalTrials.gov Identifier: NCT00359294     History of Changes
Other Study ID Numbers: PM104-A-002-05
Study First Received: August 1, 2006
Last Updated: April 20, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by PharmaMar:
Tumor
Lymphoma
Zalypsis
PharmaMar
PM00104

Additional relevant MeSH terms:
Lymphoma
Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 20, 2014