Ewing's SarcomaPhase 2NCT01222767
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
A Phase 2 study testing Zalypsis in people with Ewing's Sarcoma and Primitive Neuroectodermal Tumor (PNET), run by PharmaMar at 7 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Ewing's Sarcoma, Primitive Neuroectodermal Tumor (PNET), Askin's Tumor of the Chest Wall
- What is being tested?
- Zalypsis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 7 sitesin 3 countries
- Study dates
- Dec 2010to Apr 2012
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 17Show fewer
- 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.
- Left ventricular ejection fraction (LVEF) within normal limits (LVEF of at least 50%).
- 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).
Who cannot join
- 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.
Show all 26Show fewer
- 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).
- 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.
- 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.
- Treatment with any investigational product within 30 days prior to inclusion in the study.
- Known hypersensitivity to any component of Zalypsis®.
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States3 sites
St. Jude Children 's Research Hospital
Memphis, Tennessee, 38105A
Sarcoma Oncology Center
Santa Monica, California, 90403
Seattle Cancer Care Alliance
Seattle, Washington
Italy3 sites
Istituto Ortopedici Rizzoli
Bologna, 40136
Istituto Nazionale dei Tumori
Milan, 20133
Istituto Clinico Humanitas
Rozzano, 20089
About this study
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
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)
- Being tested
- Zalypsis
- Keywords
- EFT, PNET, EOE
- Medical subject headings
- Sarcoma, Ewing, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZalypsisDrug
Also called PM00104
Zalypsis is provided as a lyophilized powder for concentrate for solution for infusion in a strength of 2.5 mg/vial.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: Zalypsis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years
Secondary outcomes (10)
Best Tumor Response
Best tumor response was defined as the best response achieved during the study according to RECIST v1.1 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
Measured: At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years
Progression-free Survival
Progression-free survival (PFS), defined as the time 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.
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
Measured: 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
Progression-free survival (PFS), defined as the time 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.
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
Measured: At 3 months
Overall Survival
Overall survival (OS), defined as the time from the first day of treatment to the date of death (or the last day when the patient was known to be alive). Survival was to be followed for up to six months after the last treatment visit of the last patient, or 12 months after the last patient was included, whichever occurred first.
Measured: from the first day of treatment to the date of death, up to 2 years
Overall Survival Rate at 6 Months
Overall survival (OS), defined as the time from the first day of treatment to the date of death (or the last day when the patient was known to be alive). Survival was to be followed for up to six months after the last treatment visit of the last patient, or 12 months after the last patient was included, whichever occurred first.
Measured: At 6 months
Overall Survival Rate at 12 Months
Overall survival (OS), defined as the time from the first day of treatment to the date of death (or the last day when the patient was known to be alive). Survival was to be followed for up to six months after the last treatment visit of the last patient, or 12 months after the last patient was included, whichever occurred first.
Measured: At 12 months
PM00104 Plasma PK Parameters (Cmax) at First Infusion
Cmax Maximum plasma concentration, directly determined from the experimental data
Measured: 0 (Pre-infusion) and 5 min, 30 min, 2 hours, 6 hours, 24 hours, 48 hours and 168 hours after the end of first infusion (Day 1)
PM00104 Plasma PK Parameters (AUC) at First Infusion
AUC Area under the plasma concentration-time curve from time zero to infinity
Measured: 0 (Pre-infusion) and 5 min, 30 min, 2 hours, 6 hours, 24 hours, 48 hours and 168 hours after the end of first infusion (Day 1)
PM00104 Plasma PK Parameters (Cmax) at Second Infusion
Cmax Maximum plasma concentration, directly determined from the experimental data
Measured: 0 (Pre-infusion) and 5 min, 30 min, 2 hours, 6 hours, 24 hours, 48 hours and 168 hours after the end of second infusion (Day 8)
PM00104 Plasma PK Parameters (AUC) at Second Infusion
AUC Area under the plasma concentration-time curve from time zero to infinity
Measured: 0 (Pre-infusion) and 5 min, 30 min, 2 hours, 6 hours, 24 hours, 48 hours and 168 hours after the end of second infusion (Day 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startDec 2010
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ewing's SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaMar
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Fariba Navid, MD, Principal investigator, St. Jude Children 's Research HospitalSant P Chawla, MD, Principal investigator, Sarcoma Oncology CenterJean Yves Blay, MD, Principal investigator, Centre Leon BerardStefano Ferrari, MD, Principal investigator, Istituto Ortopedici RizzoliArmando Santoro, Prof., Principal investigator, Istituto Clinico HumanitasPaolo Casali, MD, Principal investigator, Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoRobin L. Jones, MD, Principal investigator, Seattle Cancer Care Alliance
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222767
- Sponsor's protocol ID
- PM104-B-003-10
- Status last verified
- Jul 2021
- First submitted
- 8 Oct 2010
- Last updated
- 29 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No