Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

Pharmaceutical Solutions

All Drugs and Chemicals

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

Zalypsis

Fariba Navid, MD

Sant P Chawla, MD

Jean Yves Blay, MD

Stefano Ferrari, MD

Armando Santoro, Prof.

Paolo Casali, MD

Robin L. Jones, MD

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.

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

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

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

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

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

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.

Cmax Maximum plasma concentration, directly determined from the experimental data

AUC Area under the plasma concentration-time curve from time zero to infinity

PharmaMar

Sixteen of 17 patients included in this study were treated with PM00104 and were therefore evaluable for safety

PM00104 was administered at a dose of 2 mg/m2 as a 1-hour i.v. infusion d1, d8 and d15 q4wk to patients with advanced and/or metastatic Ewing's sarcoma previously treated with at least one line of chemotherapy. A treatment cycle consisted of PM00104 administration on Days 1, 8 and 15, plus one week of follow-up. Study evaluations had to be completed during each cycle prior to subsequent PM00104 infusion. Treatment cycles were repeated every four weeks

PM00104

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Italy

France

Region of Enrollment

Eastern Cooperative Oncology Group Performance Status, ECOG PS 0 Fully active, able to carry on all pre-disease performance without restriction

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
2. Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
3. Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4. Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5. Dead

ECOG PS

Tumor diagnosis

Primary location at diagnosis

Metastatic disease

Time from diagnosis to first infusion

Time from last disease progression to first infusion

Sites of disease at diagnosis

Prior radiotherapy

Prior Antitumor surgery (palliative or curative)

Prior Systemic anticancer therapy

Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit.

Overall Response Rate (ORR)

One patient never treated Two patients were non-evaluable for efficacy because they were withdrawn due to toxicity without any tumor assessment after the start of study treatment and were considered as "treatment failures"

Best Tumor Response

Progression-free Survival

Progression-free Survival at 3 Months

Overall Survival

Overall Survival Rate at 6 Months

Overall Survival Rate at 12 Months

Fourteen of the 16 patients treated in this study had plasma profiles

PM00104 Plasma PK Parameters (Cmax) at First Infusion

PM00104 Plasma PK Parameters (AUC) at First Infusion

Eleven of the 16 patients treated in this study had plasma profiles at second infusion

PM00104 Plasma PK Parameters (Cmax) at Second Infusion

PM00104 Plasma PK Parameters (AUC) at Second Infusion

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Zalypsis (PM00104) (2.5 mg/vial) is provided as a powder for concentrate for solution for infusion

Zalypsis ( PM00104)

This study is a phase II clinical and pharmacokinetic trial of PM00104 (Zalypsis®) in patients with advanced and/or metastatic endometrial or cervical cancer previously treated with one line of systemic chemotherapy to evaluate the antitumor activity and to determine the safety profile, the pharmacokinetic profile and the pharmacogenomic profile.

Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy

Phase II Clinical and Pharmacokinetic Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy

Overall Response Rate defined as the percentage of patients with either complete response (CR) or partial response (PR) according to RECIST v.1.0.

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

Best tumor response was defined as the best response achieved during the study according to RECIST v1.0 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

Progression-free survival (PFS) was defined as the time from the date of first infusion of study treatment to the date of progression or death (due to any cause). If progression or death had not occurred at the time of the analysis, PFS was censored on the date of last tumor evaluation.

PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density

Progression-free survival rate at 4 months was defined as the percentage of patients who did not progress and were alive at 4 months.

PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density

Overall survival (OS) was defined as the time from the date of first infusion of study treatment to the date of death (due to any cause). Patients with no documented death were censored at the last date they were known to be alive

AUC Area under the plasma concentration-time curve from time zero to infinity.

Patients with Endometrial Cancer. A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks.

Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials

Endometrial Cancer

Patients with Cervical Cancer A treatment cycle consisted of the administration of i.v. 1-hour infusions of PM00104 on Day 1, Day 8 and Day 15, and all study evaluations done before the next cycle. Treatment cycles were to be repeated every four weeks.

Study treatment was administered to patients by a central catheter and by specialized on-site study personnel. A central catheter was mandatory as some cases of infusion site reactions were observed in the phase I trials

Cervical Cancer

Total

Race/Ethnicity, Customized

Eastern Cooperative Oncology Group Performance Status

Histology

Extent of disease

Low grade or grade I tumors are well-differentiated. This means that the tumor cells are organized and look more like normal tissue.

High grade or grade III tumor cells are poorly differentiated. This means that the tumor cells don't look like normal cells. They're disorganized under the microscope and tend to grow and spread faster than grade I tumors.

Cancer cells that don't look well-differentiated or poorly differentiated are called moderately differentiated, or grade II.

Histology grade

Sites involved

Time from last progression to first infusion

Prior Surgery

Two patients were not evaluable for efficacy: One patient received only one PM00104 infusion in Cycle 1 and had to be withdrawn from the study due to a troponin I increase, which occurred seven days after the first infusion of PM00104 and was considered serious (SAE) and related to PM00104; One patient only received one PM00104 infusion and was withdrawn from the study due to drug-unrelated marantic endocarditis

Progression Free Survival

Progression Free Survival Rate at 4 Months

Zalypsis (PM00104): Zalypsis (PM00104) (2.5 mg/vial) is provided as a powder for concentrate for solution for infusion

All treated patients with second infusion

All treated patients with Second infusion

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

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

Roger Bryan Cohen, MD

Eunice Lee Kwak, MD

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.

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.

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

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.

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

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,

All patients treated with PM00104 were evaluable for safety

All patients were to receive treatment for at least one 3-week cycle, which consisted of PM00104 administrations daily for 5 days and all study evaluations up to the next treatment cycle. Cycles were to be repeated every three weeks until disease progression, unacceptable toxicity, intercurrent serious illness, withdrawal of informed consent by the patient, Investigator's opinion, or treatment delay \> 2 weeks. Patients were considered to be on study for the duration of their treatment and for the first 30 days following treatment discontinuation, defined as the day of the last PM00104 administration

Dose-level I

Dose-level II

Dose-level III

Dose-level IV

Dose-level V

Caucasian

Asian

PS 0

PS 1

Eastern Cooperative Oncology Group (ECOG) performance status (PS). 0 Fully active, able to carry on all pre-disease performance without restriction; 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2 Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; 3 Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; 4 Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; 5 Dead

Primary tumor

Prior chemotherapy

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	Ewing's Sarcoma Primitive Neuro... Askin's Tumor o... Extraosseous Ew...	Zalypsis	16 Years -	PharmaMar
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	Ewing's Sarcoma Primitive Neuro... Askin's Tumor o... Extraosseous Ew...	Zalypsis	16 Years -	PharmaMar
Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy	NCT00900562	Uterine Cervica... Endometrial Can...	Zalypsis ( PM00...	18 Years -	PharmaMar
A Phase I Study of Zalypsis (PM00104) in Subjects With Advanced Malignant Solid Tumors or Lymphoma	NCT00359294	Solid Tumors Lymphoma	PM00104	18 Years -	PharmaMar
A Phase I Study of Zalypsis (PM00104) in Subjects With Advanced Malignant Solid Tumors or Lymphoma	NCT00359294	Solid Tumors Lymphoma	PM00104	18 Years -	PharmaMar

Spots Global Cancer Trial Database for zalypsis

Every month we try and update this database with for zalypsis cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for zalypsis

Every month we try and update this database with for zalypsis cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for zalypsis cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.