Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Chlorotrianisene

Liver Extracts

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Chemoembolization using LC Bead LUMI™ (Radiopaque (RO) Bead) loaded with doxorubicin

Drug Eluting Beads loaded with chemotherapy

LC Bead LUMI™ (Radiopaque (RO) Bead) loaded with doxorubicin

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. This type of cancer may be "hypervascular". Hypervascular means there is an increased number or concentration of blood vessels. These blood vessels get their blood supply from the hepatic artery, while the non-tumor liver tissue gets blood supply from the portal vein. Therefore, blockage of the hepatic artery to cut off the blood supply to the tumor is possible without affecting the normal liver.

This research protocol will study chemoembolization using radiopaque beads loaded with a chemotherapy drug called doxorubicin. Chemoembolization is a procedure in which the blood supply to a tumor is blocked after anticancer drugs are given in blood vessels near the tumor. In this study, the anticancer drug, doxorubicin, is attached to small beads that are injected into an artery that feeds the tumor. The radiopaque beads (RO beads) are visible on imagining scans (X-rays) so that the Interventional Radiologist performing the chemoembolization procedure can see the location of the beads in the tumor during and after the procedure. The visibility of the beads allows the interventional radiologist to confirm where the beads loaded with doxorubicin have been delivered in the tumor; this in theory could help to improve the efficiency of embolization and plan the next course of treatment. In addition to the embolization, the beads elute a sustained dose of doxorubicin locally to the tumor site as a second effect.

The usual treatment for HCC is to perform a procedure to the tumor known as Transarterial Chemo-Embolization (TACE). TACE has been approved and used worldwide for over 10 years.

Transarterial means that the treatment is delivered using a catheter inserted into the hepatic artery. Embolization is a treatment that blocks or slows down the blood supply to tissues. This procedure is performed to block the flow of blood to a tumor, so the cancer cells die because the oxygen supply is interrupted. When the material used to block the blood supply also delivers a chemotherapy drug to the tumor, it is called chemoembolization. The most commonly used material for chemoembolization are drug-eluting beads (DEBs) that are loaded with a chemotherapy drug (doxorubicin). These beads are not visible, during the procedure, on the imaging (scanner, ultrasonography or MRI) while injected into the tumor. The consequences of the blood flow interruption are visible on imaging (CT, MRI) in the weeks following treatment (tissue infarction/tumor necrosis).

This study uses the LC Bead LUMI™ radiopaque beads (RO beads). The difference is that RO Beads are visible with X-Ray imaging (scanner, fluoroscopy). This is important because it means that the Interventional Radiologist is able to verify, during the procedure, where the beads have been delivered to the tumor. The Interventional Radiologist will identify the blood supply to the tumor, and then inject the LC Bead LUMI™ loaded with doxorubicin and a compatible contrast agent into the blood vessels that supply the liver tumor. These RO beads block the blood vessel, starve the tumor of nutrients and deliver a slow release of the doxorubicin.

Many of the tests, investigations and procedures that will be requested as a part of the study may be the same as what is routinely done in the diagnosis and treatment of HCC. These tests will be used to determine if you are eligible to participate in this study and receive the LC Bead LUMI™ loaded with doxorubicin. Some of the study assessments are done to evaluate the safety and efficacy of the treatment procedure and others will be done for research purposes.

During the study, the tests and evaluations will be scheduled with normally occurring appointments, when possible; to reduce the number of visits the patient needs to make to the study center. Study visits for tumor response evaluation occur at one month after the first treatment then every 3 months for 2 years then every 6 months.

The information obtained during your visits will help your study doctor determine what choices you have for the next best course of action in treating your cancer. Options may include; repeat the study treatment, propose another alternative treatment or to continue the follow-up.

Study in the Treatment of HCC With a Radiopaque (RO) Bead (LC Bead LUMI™) Loaded With Doxorubicin

A Prospective, US Multicenter Open Label Study in the Treatment of Hepatocellular Carcinoma (HCC) With a Radiopaque (RO) Bead (LC Bead LUMI™) Loaded With Doxorubicin

Time when progression is first observed at a tumor assessment according to mRECIST evaluated by CT scan or MRI.

The incidence of treatment emergent AE's and SAE's will be summarized according to the standardized grading criteria (NCI CTCAEv4.0).

ORR is defined as a complete response or partial response, DCR is defined as a complete response, partial response or stable disease, according to mRECIST evaluated by CT or MRI.

Progression of Target Lesion response according to mRECIST evaluated by CT or MRI.

Assessment of overall survival for all subjects until death any cause

Investigator rating of deposition and handling of the study device

Biocompatabilities UK Ltd

Boston Scientific Corporation

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Small Cell Lung Carcinoma

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Antirheumatic Agents

Cyclophosphamide

Topotecan

Vincristine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Topoisomerase I Inhibitors

CAV (Cyclophosphamide (CTX), Doxorubicin (DOX) and Vincristine (VCR))

Lurbinectedin (PM01183)

Doxorubicin (DOX)

Cyclophosphamide (CTX)

Vincristine (VCR)

Phase III randomized clinical trial of lurbinectedin (PM01183)/doxorubicin (DOX) versus cyclophosphamide (CTX), doxorubicin (DOX) and vincristine (VCR) (CAV) or topotecan as treatment in patients with small-cell lung cancer (SCLC) who failed one prior platinum-containing line.

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of an experimental arm consisting of PM01183/DOX combination followed by PM01183 alone, if applicable vs. best Investigator's choice between CAV or topotecan as a control arm, in SCLC patients who failed one prior platinum-containing line but no more than one prior chemotherapy-containing line.

Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus CAV or Topotecan as Treatment in Patients With Small-Cell Lung Cancer

Phase III Randomized Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus Cyclophosphamide, Doxorubicin and Vincristine (CAV) or Topotecan as Treatment in Patients With Small-Cell Lung Cancer (SCLC) Who Failed One Prior Platinum-containing Line (ATLANTIS)

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

Progression-free survival (PFS) is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death). If the patient receives further antitumor therapy or is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment before the date of subsequent antitumor therapy.

Best antitumor response will be the best response obtained in any evaluation according to 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; UK,unknown

Overall response rate is defined as the proportion of patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to 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; UK,unknown

Duration of Response is defined as the time that patients who have a partial or complete response in the best antitumor response. The best antitumor response will be the best response obtained in any evaluation according to 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; UK,unknown

PharmaMar

21 of 613 randomized patients did not receive the study treatment. Safety population consisted of 592 treated patients. 302 had been randomized to lurbinectedin/DOX and 290 to topotecan or CAV. However, one patient randomized to receive topotecan was treated with lurbinectedin/DOX instead. For safety data analysis, this patient has been moved to the lurbinectedin/DOX Arm, and the safety population thereby comprised 303 patients with lurbinectedin/DOX and 289 patients with topotecan or CAV.

Doxorubicin: 40.0 mg/m2 i.v. on Day 1 through peripheral or central lines (according to local label), followed by, Lurbinectedin: 2.0 mg/m2 i.v. as a 1-hour infusion on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines. A minimum volume of 100 mL diluted in 5% glucose or 0.9% sodium chloride solution for infusion, had to be used for administration through a central venous catheter; if a peripheral venous catheter was used, the minimum volume was 250 mL.

The combination was to be administered for up to a maximum of ten cycles.

Lurbinectedin/Doxorubicin

If the patient was randomized to the Control Arm, the assigned treatment was based on the reported Investigator's preference between topotecan and CAV, until the first of these options had reached 55% of the target patient enrollment in this arm. Once this had occurred, patients in the Control Arm were to receive the other option.

Topotecan: i.v. daily on Days 1-5 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines (according to local label) at the following doses:

* 1.50 mg/m2 daily, for patients with calculated CrCL ≥60 mL/min.
* 1.25 mg/m2 daily, for patients with calculated CrCL between 40 and 59 mL/min.
* 0.75 mg/m2 daily, for patients with calculated CrCL between 30 and 39 mL/min.

If the patient was randomized to the Control Arm, the assigned treatment was based on the reported Investigator's preference between topotecan and CAV, until the first of these options had reached 55% of the target patient enrollment in this arm. Once this had occurred, patients in the Control Arm were to receive the other option.

CAV: i.v. on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines at the following doses:

* Cyclophosphamide: 1000 mg/m2,
* Doxorubicin: 45.0 mg/m2,
* Vincristine: 2.0 mg FD. The triple combination was to be administered for up to a maximum of ten cycles

Cyclophosphamide/Doxorubicin/Vincristine

If the patient was randomized to the Control Arm, the assigned treatment was based on the reported Investigator's preference between topotecan and CAV, until the first of these options had reached 55% of the target patient enrollment in this arm. Once this had occurred, patients in the Control Arm were to receive the other option.

Topotecan: i.v. daily on Days 1-5 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines (according to local label) at the following doses:

* 1.50 mg/m2 daily, for patients with calculated CrCL ≥60 mL/min.
* 1.25 mg/m2 daily, for patients with calculated CrCL between 40 and 59 mL/min.
* 0.75 mg/m2 daily, for patients with calculated CrCL between 30 and 39 mL/min.

or

CAV: i.v. on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines at the following doses:

* Cyclophosphamide: 1000 mg/m2,
* Doxorubicin: 45.0 mg/m2,
* Vincristine: 2.0 mg flat dose. The triple combination was to be administered for up to a maximum of ten cycles

Topotecan or Cyclophosphamide/Doxorubicin/Vincristine

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Argentina

Romania

Hungary

United States

Czechia

United Kingdom

Portugal

Spain

Greece

Lebanon

Canada

Austria

Netherlands

Belgium

Brazil

Poland

Italy

Bulgaria

France

Germany

Region of Enrollment

Weight

Height

Body surface area

Body mass index

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

Eastern Cooperative Oncology Group Performance Status

Smoking status

Time from first diagnosis to randomization

Limited stage. Limited stage means that the cancer is only in 1 part of the chest and radiation therapy could be a treatment option.

Extensive stage. Extensive stage is used to describe SCLC that has spread to other parts of the body such as the opposite lung, bone, brain, or bone marrow.

Disease stage

Number of sites involved

Bulky disease defined as one lesion ≥50 mm

Bulky disease

Central Nervous System involvement

Paraneoplastic syndrome

Prior radiotherapy

Prior surgery

Lines of anticancer therapy

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; Unknown (UK)

Best response to last prior chemotherapy

PD-1, programmed cell death protein-1; PD-L1, programmed death ligand-1

Prior immunotherapy against PD-1 or PD-L1

Time-to-progression to prior chemotherapy

Time from last prior progressive disease to randomization

Time from end date of last prior chemotherapy to randomization

Chemotherapy-free interval

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

If the patient was randomized to the Control Arm, the assigned treatment was based on the reported Investigator's preference between topotecan and CAV, until the first of these options had reached 55% of the target patient enrollment in this arm. Once this had occurred, patients in the Control Arm were to receive the other option.

Topotecan: i.v. daily on Days 1-5 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines (according to local label) at the following doses:

* 1.50 mg/m2 daily, for patients with calculated CrCL ≥60 mL/min.
* 1.25 mg/m2 daily, for patients with calculated CrCL between 40 and 59 mL/min.
* 0.75 mg/m2 daily, for patients with calculated CrCL between 30 and 39 mL/min.

or

CAV: i.v. on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines at the following doses:

* Cyclophosphamide: 1000 mg/m2,
* Doxorubicin: 45.0 mg/m2,
* Vincristine: 2.0 mg flat dose (FD). The triple combination was to be administered for up to a maximum of ten cycles

Overall Survival (OS)

If the patient was randomized to the Control Arm, the assigned treatment was based on the reported Investigator's preference between topotecan and CAV, until the first of these options had reached 55% of the target patient enrollment in this arm. Once this had occurred, patients in the Control Arm were to receive the other option.

Topotecan: i.v. daily on Days 1-5 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines (according to local label) at the following doses:

* 1.50 mg/m2 daily, for patients with calculated CrCL ≥60 mL/min.
* 1.25 mg/m2 daily, for patients with calculated CrCL between 40 and 59 mL/min.
* 0.75 mg/m2 daily, for patients with calculated CrCL between 30 and 39 mL/min.

or

CAV: i.v. on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines at the following doses:

* Cyclophosphamide: 1000 mg/m2,
* Doxorubicin: 45.0 mg/m2,
* Vincristine: 2.0 mg FD. The triple combination was to be administered for up to a maximum of ten cycles

Patients with Cyclophosphamide, Doxorubicin and Vincristine (CAV) as best Investigator's choice

Difference in Overall Survival Between Lurbinectedin/Doxorubicin (DOX) and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 12 Months

Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 18 Months

Difference in Overall Survival Between Lurbinectedin/DOX and CAV in Patients With CAV as Best Investigator's Choice: Overall Survival Rate at 24 Months

Progression-free Survival (PFS) by Independent Review Committee

Progression-free Survival Rate at 6 Months by Independent Review Committee

Progression-free Survival Rate at 12 Months by Independent Review Committee

Best Antitumor Response by Independent Review Committee

Overall Response Rate by Independent Review Committee

Patients who have a partial or complete response in the best antitumor response

Duration of Response by Independent Review Committee

A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval ≥90 days after first-line chemotherapy

Overall Survival in Patients With Chemotherapy-free Interval ≥ 90 Days

Progression-free Survival in Patients With Chemotherapy-free Interval ≥90 Days

Best Antitumor Response in Patients With Chemotherapy-free Interval ≥ 90 Days

Overall Response Rate in Patients With Chemotherapy-free Interval ≥ 90 Days

Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval ≥90 days after first-line chemotherapy.

Duration of Response in Patients With Chemotherapy-free Interval ≥ 90 Days

A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval \<90 days after first-line chemotherapy

Overall Survival in Patients With Chemotherapy-free Interval < 90 Days

Progression-free Survival in Patients With Chemotherapy-free Interval <90 Days

Best Antitumor Response in Patients With Chemotherapy-free Interval <90 Days

Overall Response Rate in Patients With Chemotherapy-free Interval <90 Days

Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients had chemotherapy-free interval \<90 days after first-line chemotherapy.

Duration of Response in Patients With Chemotherapy-free Interval <90 Days

A preplanned exploratory efficacy subgroup analysis was focused on patients without Central Nervous System Involvement at Baseline

Overall Survival in Patients Without Central Nervous System Involvement at Baseline

Progression-free Survival in Patients Without Central Nervous System Involvement at Baseline

Best Antitumor Response in Patients Without Central Nervous System Involvement at Baseline

Overall Response Rate in Patients Without Central Nervous System Involvement at Baseline

Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients without Central Nervous System Involvement at Baseline

Duration of Response in Patients Without Central Nervous System Involvement at Baseline

A preplanned exploratory efficacy subgroup analysis was focused on patients with Central Nervous System Involvement at Baseline

Overall Survival in Patients With Central Nervous System Involvement at Baseline

Progression-free Survival in Patients With Central Nervous System Involvement at Baseline

Best Antitumor Response in Patients With Central Nervous System Involvement at Baseline

Overall Response Rate in Patients With Central Nervous System Involvement at Baseline

Patients who have a partial or complete response in the best antitumor response. A preplanned exploratory efficacy subgroup analysis was focused on patients with Central Nervous System Involvement at Baseline

Duration of Response in Patients With Central Nervous System Involvement at Baseline

If the patient was randomized to the Control Arm, the assigned treatment was based on the reported Investigator's preference between topotecan and Cyclophosphamide, Doxorubicin and Vincristine (CAV), until the first of these options had reached 55% of the target patient enrollment in this arm. Once this had occurred, patients in the Control Arm were to receive the other option.

Topotecan: i.v. daily on Days 1-5 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines (according to local label) at the following doses:

* 1.50 mg/m2 daily, for patients with calculated Creatinine Clearance (CrCL) ≥60 mL/min.
* 1.25 mg/m2 daily, for patients with calculated CrCL between 40 and 59 mL/min.
* 0.75 mg/m2 daily, for patients with calculated CrCL between 30 and 39 mL/min.

or

CAV: i.v. on Day 1 q3wk (three weeks ±48h = one treatment cycle) through peripheral or central lines at the following doses:

* Cyclophosphamide: 1000 mg/m2,
* Doxorubicin: 45.0 mg/m2,
* Vincristine: 2.0 mg flat dose. The triple combination was to be administered for up to a maximum of ten cycles

Overall Study

Glioblastoma

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Immunomodulating Agents

Patients will undergo implantation of Sonocloud-9 after completion of radiotherapy. Within 21 days after implant, ultrasound-based BBB opening with concomitant administration of DOX (30 mg) + BAL (450 mg) every 3 weeks, and BOT (dose 1mg/kg) every 6 weeks will be initiated.

Balstilimab 450 mg IV over 30 minutes every 3 weeks

Balstilimab

Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks

Botensilimab

Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks

Liposomal Doxorubicin

Device activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study in the Treatment of HCC With a Radiopaque (RO) Bead (LC Bead LUMI™) Loaded With Doxorubicin	NCT03452553	Hepatocellular ...	LC Bead LUMI™ (...	18 Years -	Boston Scientific Corporation
Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus CAV or Topotecan as Treatment in Patients With Small-Cell Lung Cancer	NCT02566993	Small-cell Lung...	Lurbinectedin (... Doxorubicin (DO... Cyclophosphamid... Vincristine (VC... Topotecan	18 Years -	PharmaMar
Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin Versus CAV or Topotecan as Treatment in Patients With Small-Cell Lung Cancer	NCT02566993	Small-cell Lung...	Lurbinectedin (... Doxorubicin (DO... Cyclophosphamid... Vincristine (VC... Topotecan	18 Years -	PharmaMar
Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma	NCT05864534	Newly Diagnosed... Glioblastoma, I... Gliosarcoma Glioblastoma Mu...	Balstilimab Botensilimab Liposomal Doxor... Sonocloud-9 (SC...	18 Years -	Northwestern University

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