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

NCT00359294 | Terminated Phase 1 Results DMC

• 1 other identifier: PM104-A-002-05
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Solid Tumors; Lymphoma

Keywords

Tumor; Lymphoma; Zalypsis; PharmaMar; PM00104

Outcome Measures

Primary Outcomes (1)

• Patients With Dose Limiting Toxicities (DLT)

  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 Outcomes (1)

• Overall Best Tumor Response

  every six weeks while on study, up to 2 years

Study Arms (1)

Zalypsis (PM00104)

EXPERIMENTAL

Drug: PM00104

Interventions

PM00104 DRUG

Intravenously over 1 hour daily for 5 days, every 3 weeks.

Also known as: Zalypsis

Zalypsis (PM00104)

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Prior therapy with PM00104
• Pregnant or lactating women.
• 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).
• Prior high dose chemotherapy that needed bone marrow transplant support.
• Subjects with untreated or uncontrolled brain or meningeal metastases.
• 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.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

MeSH Terms

Conditions

Lymphoma; Neoplasms

Interventions

PM 00104

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

This phase I study was prematurely closed due to a low recruiting rate as well as to the perception that this could be an unpractical dosing schedule when compared to other schedules evaluated in the clinical development program of PM00104.

Results Point of Contact

• Title: Responsible medical officer
• Organization: PharmaMar USA Inc

ccoronado@pharmamar.com

1 212 201 6770

Study Officials

• Roger Bryan Cohen, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

• Eunice Lee Kwak, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 1, 2006
• First Posted: August 2, 2006
• Study Start: May 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: July 28, 2021
• Results First Posted: July 28, 2021

Record last verified: 2021-07

Locations

US (2)