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

NCT01222767 | Completed Phase 2 Results

• 1 other identifier: PM104-B-003-10
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 7

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.

Conditions

Ewing's Sarcoma; Primitive Neuroectodermal Tumor (PNET); Askin's Tumor of the Chest Wall; Extraosseous Ewing's Sarcoma (EOE)

Keywords

EFT; PNET; EOE

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate (ORR), defined as the percentage of patients with confirmed objective response (OR), either CR or PR according to the RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; RECIST, Response Evaluation Criteria in Solid Tumors

  At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years

Secondary Outcomes (10)

• Best Tumor Response

  At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years

• Progression-free Survival

  From the first day of study treatment to the day of negative assessment (progression or death), start of subsequent antitumor therapy, or last tumor evaluation, up to 2 years

• Progression-free Survival at 3 Months

  At 3 months

• Overall Survival

  from the first day of treatment to the date of death, up to 2 years

• Overall Survival Rate at 6 Months

  At 6 months

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: Zalypsis

Interventions

Zalypsis DRUG

Zalypsis is provided as a lyophilized powder for concentrate for solution for infusion in a strength of 2.5 mg/vial.

Also known as: PM00104

Arm 1

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written informed consent, obtained from the patient or his/her representative before the beginning of any specific study procedures.
• Age ≥ 16 years.
• Histologically or cytologically confirmed EFT (Ewing Family of Tumors), with recurrent disease.
• Documented failure to at least one prior chemotherapy regimen for their disease.
• Radiographic documentation of disease progression at study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≤ 2.
• Life expectancy ≥ 3 months.
• 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.
• 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.
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/l; platelet count ≥ 100 x 109/l, and hemoglobin ≥ 9 g/dl.
• Adequate renal function: calculated creatinine clearance (using Cockcroft and Gault's formula) ≥ 30 ml/min.
• 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.

You may not qualify if:

• Prior therapy with Zalypsis®.
• Pregnant or lactating women or women of childbearing potential not using an appropriate contraceptive method.
• Less than three weeks from prior radiation therapy, biological therapy or chemotherapy.
• 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.
• 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.
• Evidence of progressive or symptomatic central nervous system (CNS) metastases or leptomeningeal metastases.
• Other diseases or serious conditions:
• Increased cardiac risk, as defined by:
• 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.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (7)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

St. Jude Children 's Research Hospital

Memphis, Tennessee, 38105A, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, United States

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Istituto Ortopedici Rizzoli

Bologna, 40136, Italy

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

MeSH Terms

Conditions

Sarcoma, Ewing; Neuroectodermal Tumors, Primitive

Interventions

PM 00104

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit.
• Organization: Pharma Mar S.A.

clinicaltrials@pharmamar.com

0034 91846 60 00

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 18, 2010
• Study Start: December 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: October 29, 2021
• Results First Posted: October 29, 2021

Record last verified: 2021-07

Locations

IT (3); US (3); FR (1)