Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Topotecan

Topoisomerase I Inhibitors

Enzyme Inhibitors

Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)

Patients will consecutively receive the following q3wk (every three weeks = one treatment cycle):

* Irinotecan (Day 1 and Day 8)
* Lurbinectedin (Day 1)

Best Investigator's choice prior to randomization between:

* Irinotecan on Day 1 q3wk
* Topotecan on Days 1-5 q3wk

Irinotecan 75 mg/m² intravenously Days 1 \& 8 q3wk

Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 q3wk

Lurbinectedin

For patients aged \<70 years: irinotecan 350 mg/m² intravenously Day 1 q3wk For patients aged ≥70 years: irinotecan 300 mg/m² intravenously Day 1 q3wk

Topotecan 2.3 mg/m² oral or 1.5 mg/m² intravenously Days 1-5 q3wk

Lurbinectedin 2.0 mg/m² will be administered intravenously on Day 1 q3wk

José Antonio Lopez-Vilariño, MD

Florida C Specialists

Clínica S María

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of two experimental arms consisting of lurbinectedin as single agent (Group A) or the combination of lurbinectedin with irinotecan (Group B) versus Investigator's Choice (topotecan or irinotecan) as control arm (Group C), in Small-cell Lung Cancer (SCLC) patients who failed one prior platinum-containing line.

Approximately 705 Adult SCLC patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 who have failed one prior platinum-containing line with CTFI ≥ 30 days and controlled asymptomatic and pretreated Central Nervous System metastases will be enrolled and assigned to each treatment arm.

Central randomization will be implemented; patients will be assigned to each treatment arm at a 1:1:1 ratio.

An Independent Data Monitoring Committee (IDMC) will oversee the conduct of the study. The IDMC should have access to unblinded efficacy and safety data throughout the trial to enable timely and informed judgments about risks and benefits.

Multicenter, open-label, randomized, controlled

Clinical Trial of Lurbinectedin as Single-agent or in Combination With Irinotecan Versus Topotecan or Irinotecan in Patients With Relapsed Small-cell Lung Cancer (LAGOON)

A Randomized, Multicenter, Open-label, Phase III Study of Lurbinectedin Single-Agent or Lurbinectedin in Combination With Irinotecan Versus Investigator's Choice (Topotecan or Irinotecan) in Relapsed Small Cell Lung Cancer Patients (LAGOON Trial)

Overall survival (OS) will be calculated from the date of randomization to the date of death or last contact (in this case, survival will be censored on that date).

Progression-free survival (PFS) will be calculated from the date of randomization to the date of documented progression per RECIST v.1.1 (Progressive disease is declared when there is an increase in sum of target disease ≥ 20%) or death (regardless of the cause of death). If the patient receives further antitumor therapy, withdraws from the study, or is lost to follow-up before progressive disease (PD), PFS will be censored at the date of last evaluable tumor assessment before the date of subsequent antitumor therapy.

Overall response rate (ORR) will be the percentage of patients with complete or partial response as the best response obtained in any evaluation according to RECIST v.1.1. Progressive disease is declared when there is an increase in sum of target disease ≥ 20%, stable disease when the change is \> -30% and ≤ 20%, partial response when there is a decrease in sum of target disease ≥ 30%, and complete response when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each.

Overall survival rate at 12 months is defined as the percentage of people who are still alive at 12 months after randomization.

Overall survival rate at 24 months is defined as the percentage of people who are still alive at 24 months after randomization.

Progression-free survival rate at 6 months is defined as the percentage of people who remain free from progression at 6 months after randomization

Progression-free survival rate at 12 months is defined as the percentage of people who remain free from progression at 12 months after randomization

Duration of response (DoR) will be calculated from the date of first documentation of response per RECIST v.1.1 (complete or partial response, whichever occurs first) to the date of documented PD or death. Progressive disease is declared when there is an increase in sum of target disease ≥ 20%, stable disease when the change is \> -30% and ≤ 20%, partial response when there is a decrease in sum of target disease ≥ 30%, and complete response when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each.

To measure the quality of life of patients, the Lung Cancer Symptom Scale (LCSS) questionnaire will be analyzed.

PharmaMar

Pharmaceutical Solutions

Patients will receive PM14 as an i.v. infusion in a total volume of 100 mL of 0.9% sodium chloride at the first three dose escalation levels. Thereafter, the volume of infusion can be increased to 250 mL.

PM14 drug product is provided as a sterile lyophilized powder for concentrate for solution for infusion with a strength of 5.0 mg of the active moiety. Patients will receive PM14 as an i.v. infusion in a total volume of 100 mL of 0.9% sodium chloride at the first three dose escalation levels. Thereafter, the volume of infusion can be increased to 250 mL.

PM14

Carmen Kahatt, MD, PhD

Cristian Fernández, M.D.

Gregory Cote

Vivek Subbiah

Christophe Massard

Elena Garralda

Aitana Calvo

Eduardo Castañon Alvarez

Tatiana Hernández

Luis Paz-Ares

María José de Miguel Luken

Despite recent advances in the treatment of solid tumors in general, advanced (metastatic) disease remains mostly incurable and there is an urgent need to develop new therapeutic options for these patients, particularly investigational drugs with novel mechanisms of action. The investigation of new combination regimens of non-crossresistant agents with acceptable-and not completely overlapping-toxicities has been a major way to improve response rate and outcome of patients with advanced solid tumors.

First-in-human, open-label, dose-finding, phase I trial, using a classical 3+3 design followed by a continual reassessment method (CRM).

Patients will be included in cohorts of a minimum of three or six patients to receive PM14 at successively increasing dose levels, starting at 0.25 mg/m\^2 for the Days 1 and 8 schedule. For the Day 1 schedule, the starting dose will be 4.5 mg/m\^2. Dose escalation will proceed only after all the patients fully evaluable for DLT included at one dose level have completed the first cycle (i.e., three weeks). Once the RD has been determined, expansion cohorts will be included to have a minimum of 20 fully evaluable patients per indication (tumor type) treated in the Expansion phase (regardless of the schedule administered), and thus have an adequate number of patients to assess safety. The indications of these patients will be chosen depending on the efficacy data obtained during dose escalation. Patients treated at the expansion cohorts will be evaluable by the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) and/or by serum markers only in patients with prostate cancer (prostate specific-antigen \[PSA\]) or ovarian cancer (carbohydrate antigen-125 \[CA-125\]) according to the Prostate-Specific Antigen Working Group Recommendations (PSAWGR) and the Gynecologic Cancer Intergroup (GCIG) specific criteria, respectively.

First-in-human, open-label, dose-finding, phase I trial, using a classical 3+3 design followed by a continual reassessment method (CRM)

PM14 Administered Intravenously to Patients With Advanced Solid Tumors

Phase I, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM14 Administered Intravenously to Patients With Advanced Solid Tumors

To identify the dose limiting toxicities (DLTs), and to determine the maximun tolerated dose (MTD) and the recommended dose (RD) of PM14 administered i.v. on two days (Day 1 and Day 8) or on Day 1 only, both every three weeks (q3wk) over three hours to patients with advanced solid tumors.

To confirm the recommended dose (RD) determined during the Dose escalation phase, and to evaluate the antitumor activity of PM14 in terms of overall response rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1, and/or serum markers as appropriate, in patients with selected advanced solid tumors.

Clinical benefit rate in each tumor type is defined as the percentage of patients with a confirmed response (either complete response or partial response) according to the RECIST v.1.1 and/or by serum markers or with stable disease (SD) ≥4 months

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

Duration of response (DoR) is defined as the time between the date of first documentation of response to the date of documented progression or death.

Patients will be evaluable for safety if they have received at least one partial infusion of PM14. Adverse events (AEs) will be graded according to the NCI-CTCAE v.4. Additionally, treatment related discontinuations and treatment compliance (dose reduction, skipped doses and/or treatment delays due to AEs) will be described.

Pharmacokinetic analyses will be evaluated in plasma and urine by standard noncompartmental analysis. Compartmental modeling may be performed if appropriate.

To evaluate Pharmacogenetic (PGt) in germline DNA by the presence or absence of PGt polymorphisms in genes relevant for PM14 disposition

To conduct an exploratory Pharmacogenomic analysis in tumor tissue samples and ctDNA of patients treated with PM14. Quantitation of mRNA expression of selected genes involved in DNA repair mechanisms or related to the mechanism of action of PM14 by qRT-PCR. Quantitation of protein expression of these genes by IHC, in tumor tissue samples.

To conduct an exploratory Pharmacogenomic analysis in tumor tissue samples and ctDNA of patients treated with PM14.

Evaluate the presence or absence of polymorphisms in genes relevant for PM14 disposition

To conduct an exploratory Pharmacogenomic analysis in tumor tissue samples and ctDNA of patients treated with PM14. The mutational status of genes wil also be analyzed

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

3-hour infusion every 2 weeks alone or in combination with dexamethasone

Plitidepsin

Paul Richardson, MD

This is a phase II study to determine the efficacy following treatment with Aplidin® 5 mg/m2, given as a 3 hours intravenous infusion every 2 weeks, in patients with relapsed or refractory multiple myeloma (MM).

This is a phase II study to determine the efficacy following treatment with Aplidin® 5 mg/m2, given as a 3 h iv infusion every 2 weeks, in patients with relapsed or refractory multiple myeloma (MM) and to obtain the following :

* Additional pharmacokinetic information for Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM.
* To obtain additional genomic and pharmacodynamics information on MM and Aplidin.
* To assess the safety and tolerability of Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM alone or in combination with dexamethasone given orally as a 20 mg daily for 4 days
* To determine the response rate in the second cohort of patients following treatment with Aplidin®, given as a 3 hour infusion every 2 weeks, plus dexamethasone given orally as a 20 mg daily for 4 days, starting the same day of Aplidin® administration, as a second treatment stage in patients with suboptimal response to Aplidin® as single agent (progressive disease after three cycles or stable disease after four cycles).

A Study of Aplidin (Plitidepsin) 3 h iv in Subjects With Relapsing or Refractory Multiple Myeloma

"Phase II Multicenter, Open-Label, Clinical and Pharmacokinetic Study of Aplidin® As A 3-Hour Infusion Every 2 Weeks Alone or in Combination With Dexamethasone, in Pre-Treated Patients With Relapsing or Refractory Multiple Myeloma."

Complete response(CR):0 percentage the original monoclonal protein level from blood and urine Partial response(PR): ≥50 percentage reduction in the level of serum monoclonal protein Minimal response(MR):≥25 percentage to ≤ 49 percentage reduction in the level of serum monoclonal protein Stable disease: Not meeting the criteria for MR or PD. Progressive disease: \>25 percentage increase in level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation.

Treatmen failure: Reappearance of serum or urinary paraprotein

Time to Progression (TTP):date of first infusion to the date of documented progressive disease which can be defined as \>25 percentage increase in level of serum monoclonal paraprotein.

Progression Free Survival (PFS): time from the date of first infusion to the date of documented progression or death

Overall Survival (OS): time from the date of first infusion to the date of documented death

PharmaMar USA Inc.

32 patients were treated with plitidepsin as single agent;afterwards 19 of them were treated with plitidepsin+dexamethasone combination.Therefore 32+19=51 is the no. patients at risk for plitidepsin and 19 is no. of patients at risk for dexamethasone

Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks.

Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion.

Plitidepsin + Dexamethasone

Total

Age Continuous

Sex: Female, Male

0 Units of Scale

1 Units of Scale

2 Units of Scale

ECOG PS: Eastern Cooperative Oncology Group Performance Status This scale is used by doctors to assess how a patient's disease is progressing, how the disease affects the daily living abilities of patients, and determine appropriate treatment and prognosis. Scale points: 0, 1, 2, 3, 4 \& 5; 0: Fully active, able to carry on all pre-disease performance without restriction, and 5: Death

ECOG PS

Claudia Silvia Corrado M.D.

Complete response

Partial response

Minimal response

Stable Disease/No changes

Progressive Disease/Treatment failure

Per protocol - Only 29 of 32 and 18 of 19 enrolled patients were evaluable (analyzed patients)

Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response

Time to Progression (TTP)

Per protocol - Only 21 of 32 and 8 of 19 enrolled patients were evaluable (analyzed patients)

Progression Free Survival (PFS)

OS at 6 months

OS at 12 months

Per protocol - Only 21 of 32 and 8 of 19 enrolled patients were evaluable (analyzed patients. For patient of group plitidepsin + dexamethasone the median overall survival could not be calculated due to follow-up short duration. The survival rates at 6 and 12 months are provided instead.

Number of Patients With Overall Survival (OS)

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

Cmax Maximum plasma concentration, directly determined from the experimental data

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

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

Age, Categorical

Age, Continuous

Race/Ethnicity, Customized

United States

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

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 diagnosis to first infusion

Time from last progression to first infusion

Prior Surgery

Prior Systemic anticancer therapy

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

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

Overall Response Rate (ORR)

Best Tumor Response

Progression Free Survival

Progression Free Survival Rate at 4 Months

Overall Survival

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Trial of Lurbinectedin as Single-agent or in Combination With Irinotecan Versus Topotecan or Irinotecan in Patients With Relapsed Small-cell Lung Cancer (LAGOON)	NCT05153239	Relapsed Small ...	Irinotecan Lurbinectedin Irinotecan Topotecan Lurbinectedin	18 Years -	PharmaMar
Clinical Trial of Lurbinectedin as Single-agent or in Combination With Irinotecan Versus Topotecan or Irinotecan in Patients With Relapsed Small-cell Lung Cancer (LAGOON)	NCT05153239	Relapsed Small ...	Irinotecan Lurbinectedin Irinotecan Topotecan Lurbinectedin	18 Years -	PharmaMar
PM14 Administered Intravenously to Patients With Advanced Solid Tumors	NCT05076396	Advanced Solid ...	PM14	18 Years -	PharmaMar
PM14 Administered Intravenously to Patients With Advanced Solid Tumors	NCT05076396	Advanced Solid ...	PM14	18 Years -	PharmaMar
A Study of Aplidin (Plitidepsin) 3 h iv in Subjects With Relapsing or Refractory Multiple Myeloma	NCT00229203	Multiple Myelom...	Plitidepsin	18 Years -	PharmaMar
A Study of Aplidin (Plitidepsin) 3 h iv in Subjects With Relapsing or Refractory Multiple Myeloma	NCT00229203	Multiple Myelom...	Plitidepsin	18 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
Clinical Trial of Lurbinectedin as Single-agent or in Combination With Irinotecan Versus Topotecan or Irinotecan in Patients With Relapsed Small-cell Lung Cancer (LAGOON)	NCT05153239	Relapsed Small ...	Irinotecan Lurbinectedin Irinotecan Topotecan Lurbinectedin	18 Years -	PharmaMar
Trial of PM02734 Administered in Combination With Erlotinib in Patients With Advanced Malignant Solid Tumors	NCT00884845	Advanced Malign...	PM02734 and erl... Erlotinib	18 Years -	PharmaMar

Spots Global Cancer Trial Database for pharmamar

Every month we try and update this database with for pharmamar 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 pharmamar

Every month we try and update this database with for pharmamar 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 pharmamar 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.