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Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01222767
Recruitment Status : Completed
First Posted : October 18, 2010
Last Update Posted : June 5, 2012
Information provided by (Responsible Party):

Brief Summary:
This is a phase II Multicenter, Open-label, Clinical and Pharmacokinetic Study of Zalypsis® (PM00104) in Patients with Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy to determine the antitumor activity of Zalypsis.

Condition or disease Intervention/treatment Phase
Ewing's Sarcoma Primitive Neuroectodermal Tumor (PNET) Askin's Tumor of the Chest Wall Extraosseous Ewing's Sarcoma (EOE) Drug: Zalypsis Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Multicenter, Open-label, Clinical and Pharmacokinetic Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy
Study Start Date : December 2010
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Arm Intervention/treatment
Experimental: Arm 1 Drug: Zalypsis
Zalypsis is provided as a lyophilized powder for concentrate for solution for infusion in a strength of 2.5 mg/vial.
Other Name: PM00104

Primary Outcome Measures :
  1. Antitumor activity [ Time Frame: 36 months ]
    To determine the antitumor activity of Zalypsis® administered as a 1-hour intravenous (i.v.) infusion on Day 1, 8 and 15 every four weeks (d1, d8 and d15, q4wk) to patients with advanced and/or metastatic EFT.

Secondary Outcome Measures :
  1. To determine time-to-event efficacy parameters [ Time Frame: 36 months ]
  2. Safety profile and tolerability profile [ Time Frame: 36 months ]
    To characterize the safety profile and tolerability of Zalypsis® in patients with unresectable advanced and/or metastatic EFT (Ewing Family of Tumors)

  3. Pharmacokinetics profile [ Time Frame: 36 months ]
    To characterize the pharmacokinetics (PK) of Zalypsis® when administered as a single-agent to patients with EFT

  4. Pharmacodynamic profile [ Time Frame: 36 months ]
    To determine the pharmacodynamic profile by measuring the effect of Zalypsis® on the number of Ewing's sarcoma circulating tumor cells (CTCs) at different times of treatment and its correlation with the clinical outcome.

  5. Pharmacogenomic (PGx) profile [ Time Frame: 36 months ]
    To determine the pharmacogenomic (PGx) profile. Hypothesis-generating exploratory PGx analyses will be conducted to correlate the molecular parameters found in the tumor and blood samples of the patients with the clinical results achieved with Zalypsis®.

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Voluntary written informed consent, obtained from the patient or his/her representative before the beginning of any specific study procedures.
  2. Age ≥ 16 years.
  3. Histologically or cytologically confirmed EFT (Ewing Family of Tumors), with recurrent disease.
  4. Documented failure to at least one prior chemotherapy regimen for their disease.
  5. Radiographic documentation of disease progression at study entry.
  6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤ 2.
  7. Life expectancy ≥ 3 months.
  8. Complete recovery from the effects of drug-related adverse events (AEs) derived from previous treatments, excluding alopecia and grade 1 peripheral neuropathy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v. 4.0.
  9. At least one measurable lesion ("target lesion" according to the RECIST v.1.1), located in a non-irradiated area and adequately measured less than four weeks before study entry. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is clearly documented or biopsy proven.
  10. Absolute neutrophil count (ANC) ≥ 1.5 x 109/l; platelet count ≥ 100 x 109/l, and hemoglobin ≥ 9 g/dl.
  11. Adequate renal function: calculated creatinine clearance (using Cockcroft and Gault's formula) ≥ 30 ml/min.
  12. Adequate hepatic function:

    • Total bilirubin ≤ 1.5 x upper limit or normality (ULN), unless due to Gilbert's syndrome.
    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3 x ULN (≤ 5 x ULN in case of hepatic metastases), and alkaline phosphatase (AP) ≤ 2.5 x ULN (≤ 5 x ULN in case of extensive bone involvement).
    • Albumin ≥ 25 g/l.
  13. Left ventricular ejection fraction (LVEF) within normal limits (LVEF of at least 50%).
  14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for three months after discontinuation of treatment. Acceptable methods of contraception include complete abstinence, intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).

Exclusion Criteria:

  1. Prior therapy with Zalypsis®.
  2. Pregnant or lactating women or women of childbearing potential not using an appropriate contraceptive method.
  3. Less than three weeks from prior radiation therapy, biological therapy or chemotherapy.
  4. Less than six weeks from prior nitrosourea, mitomycin C, high-dose chemotherapy or radiotherapy involving the whole pelvis or over 50% of the spine, provided that acute effects of radiation treatment have resolved. Hormonal therapy and palliative radiation therapy (i.e., for control of pain from bone metastases) must be discontinued before study entry.
  5. Patients with a prior invasive malignancy (except non-melanoma skin cancer and in situ cervix carcinoma) who have had any evidence of disease within the last five years or whose prior malignancy treatment contraindicates the current protocol therapy.
  6. Evidence of progressive or symptomatic central nervous system (CNS) metastases or leptomeningeal metastases.
  7. Other diseases or serious conditions:

    • Increased cardiac risk, as defined by:

      • Unstable angina or myocardial infarction within 12 months before inclusion in the study.
      • New York Heart Association (NYHA) grade II or greater congestive heart failure.
      • Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment.
      • Abnormal electrocardiogram (ECG), i.e., patients with the following are excluded: QT prolongation - QTc > 480 msec; signs of cardiac enlargement or hypertrophy; bundle branch block; partial blocks; signs of ischemia or necrosis, and 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 exceeding 400 mg/m2.
    • History of significant neurological or psychiatric disorders.
    • Active infection requiring systemic treatment.
    • Significant non-neoplastic liver disease (e.g., cirrhosis).
    • Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
    • Immunocompromised patients, including those known to be infected with the human immunodeficiency virus (HIV).
    • Uncontrolled (i.e., requiring relevant changes in medication within the last month or hospital admission within the last three months) endocrine diseases (e.g., diabetes mellitus, hypo- or hyperthyroidism, adrenal disorder).
  8. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in the study. The Investigator should feel free to consult the Study Coordinator or the Sponsor(s) in case of uncertainty in this regard.
  9. Limitation of the patient's ability to comply with the treatment or to follow-up at a participating center. Patients enrolled into this trial must be treated and followed at a participating center.
  10. Treatment with any investigational product within 30 days prior to inclusion in the study.
  11. Known hypersensitivity to any component of Zalypsis®.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01222767

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United States, California
Sarcoma Oncology Center
Santa Monica, California, United States, 90403
United States, Tennessee
St. Jude Children 's Research Hospital
Memphis, Tennessee, United States, 38105A
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States
Centre Léon Bérard
Lyon, France, 69373
Istituto Ortopedici Rizzoli
Bologna, Italy, 40136
Istituto Nazionale dei Tumori
Milan, Italy, 20133
Istituto Clinico Humanitas
Rozzano, Italy, 20089
Sponsors and Collaborators
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Principal Investigator: Fariba Navid, MD St. Jude Children 's Research Hospital
Principal Investigator: Sant P Chawla, MD Sarcoma Oncology Center
Principal Investigator: Jean Yves Blay, MD Centre Leon Berard
Principal Investigator: Stefano Ferrari, MD Istituto Ortopedici Rizzoli
Principal Investigator: Armando Santoro, Prof. Istituto Clinico Humanitas
Principal Investigator: Paolo Casali, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Principal Investigator: Robin L. Jones, MD Seattle Cancer Care Alliance
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Responsible Party: PharmaMar Identifier: NCT01222767    
Other Study ID Numbers: PM104-B-003-10
First Posted: October 18, 2010    Key Record Dates
Last Update Posted: June 5, 2012
Last Verified: June 2012
Keywords provided by PharmaMar:
Additional relevant MeSH terms:
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Sarcoma, Ewing
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial