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

July 7, 2021 updated by: PharmaMar

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.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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, Good clinical practice (GCP) and applicable regulatory requirements.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Massachusetts General Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 thromboplastin within normal limits for the institution
    • International normalized ratio (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, Intrauterine device, 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-corrected QT interval > 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zalypsis (PM00104)
Intravenously over 1 hour daily for 5 days, every 3 weeks.
Other Names:
  • Zalypsis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patients With Dose Limiting Toxicities (DLT)
Time Frame: During the first cycle (21 days)

DLTs were defined as follows:

  • Hematological adverse events:

    • Any grade 4 neutropenia (absolute neutrophil count (ANC) < 0.5 x109/l) for longer than five days;
    • Any grade 4 neutropenia accompanied by fever (at least 38.5°C);
    • Any grade 4 neutropenia and sepsis or other severe infection;
    • Any grade 4 thrombocytopenia.
  • Any other grade 3/4 non-hematological adverse event (AE) and any increase of cardiac troponin I ≥0.1 ng/ml together with evidence of cardiac damage by electrocardiogram (ECG) or echocardiogram (ECHO), except for untreated nausea/vomiting or hypersensitivity reactions.
  • Decrease in left ventricular ejection fraction (LVEF) > 20% compared to the patient's baseline value and/or LVEF < 50% below normal limits for the institution.
  • Delay in the initiation of a subsequent dose exceeding two weeks due to drug related AEs
During the first cycle (21 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Best Tumor Response
Time Frame: every six weeks while on study, up to 2 years
Best tumor response was defined as the best response achieved during the study according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response (CR): disappearance of all lesions; Partial response (PR): ≥10% decrease in target lesion size or ≥15% decrease in tumor density; Disease progression (PD): ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; Stable disease (SD): none of the CR, PR, or PD criteria met; RECIST,
every six weeks while on study, up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Roger Bryan Cohen, MD, Fox Chase Cancer Center
  • Principal Investigator: Eunice Lee Kwak, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

August 1, 2006

First Submitted That Met QC Criteria

August 1, 2006

First Posted (Estimate)

August 2, 2006

Study Record Updates

Last Update Posted (Actual)

July 28, 2021

Last Update Submitted That Met QC Criteria

July 7, 2021

Last Verified

July 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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