Symptoms and General Pathology

All Conditions

Behaviors and Mental Disorders

Disease Progression

Quality of Life

Antineoplastic Agents

All Drugs and Chemicals

Apatinib

Lenvatinib

Angiogenesis Inhibitors

Immunomodulating Agents

Sorafenib

Immunologic Factors

2000 patients with advanced hepatobiliary tumors will be enrolled and the enroll patients should be treat with any type of the following three treatment program:

1. Monotherapy or combination therapy with the targeted drug related to genetic variation of the subject;
2. Treatment with pan-target anti-angiogenic drugs, such as sorafenib, regorafenib, lenvatinib, apatinib, etc;
3. Immunotherapy or immunotherapy combined with targeted therapy or (and) chemotherapy.

Therapeutic regimens are based on the clinicopathological features, genomic alterations, advices from multidisciplinary tumor board and willings from patients.

Precision oncology including targeted therapy and immunotherapy

Xiaobo Yang

Haitao Zhao

The investigators design a large sample size study in the real-world to explore whether targeted therapy and immunotherapy can improve the survival, quality of life and drug safety of patients with advanced hepatobiliary tumors, and analyze the correlation between genetic variation and the effectiveness of therapy.

This trial is a multicenter, non-random, open and observational real-world study. It is estimated that 2000 patients with advanced hepatobiliary tumors will be enrolled in about 20 research centers. And it is planned to complete the enrollment within 2 years and it is expected that all enrolled subjects will reach the observation end point in 5 years.

After primary screening of all the patients, the investigators will further collect next-generation sequence(NGS) data and immunohistochemical data from the subjects, and enroll patients with any type of the following three treatment program: 1. Monotherapy or combination therapy with the targeted drug related to genetic variation of the subject; 2. Treatment with pan-target anti-angiogenic drugs, such as sorafenib, regorafenib, lenvatinib, apatinib, etc; 3. Immunotherapy or immunotherapy combined with targeted therapy.

The investigators will collect subjects' data from assessment centers each month and the efficacy, quality of life, and safety of treatment will be evaluated.

This trial plans to conduct an interim analysis and final analysis after collecting 500 cases, 1000 cases, and 2000 subjects, 3000 subjects,and explore the clinical application value of targeted therapy and immunotherapy in advanced hepatobiliary tumors in real world.

Real-world Study for Patients With Advanced Hepatobiliary Tumors

Real-world Study for Targeted Therapy and Immunotherapy in Patients With Advanced Hepatobiliary Tumors: a Multi-centers, Open-assess Observational Study.

Time from the date of initial treatment to death for any cause.

A duration from the date of initial treatment with apatinib to disease progression (as defined by RECIST) or death.

Percentage of subjects with complete response and partial response.

Percentage of subjects with complete remission, partial remission, or stable disease during treatment or within 30 days of termination of test drug.

Percentage of subjects who develop any adverse events (CTCAE 4.0).

The life quality of every subject will be assessed every 3 months according to the 45-item FACT-Hep questionnaire, which assesses generic HRQL concerns and disease-specific issues.

OrigiMed

Peking Union Medical College Hospital

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Carboplatin

Celecoxib

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

celecoxib (200 mg tablets by mouth twice daily, day 1 to 28), associated to intravenous carboplatin (area under the curve (AUC) 5 over 30 to 60 minutes, every 28 days).

Carboplatin plus Celecoxib

Giovanni sCAMBIA, PhD

The aim of this study is to evaluate the antitumor activity and potential adverse effects of the combination celecoxib plus carboplatin in patients with recurrent, heavily pre-treated Ovarian Cancer (OC). The potential changes induced by the experimental combination on angiogenesis-related serum markers and quality of life measures will be also evaluated.The main objective is to evaluate the response rate. Secondary objectives are the following:toxicity;progression free survival;overall survival;duration of response;quality of life;modulation of angiogenesis-related molecules.

This phase II prospective study will be conducted at the Gynecologic Oncology Units of the Catholic University of Rome and Campobasso, Italy. The study is non-sponsored, investigators initiated. The primary objective is to determine the tumor response rate by RECIST criteria. Secondary objectives included duration of response, progression-free survival (PFS), overall survival (OS), toxicity assessment, and QoL measures.Patients are required to take celecoxib (200 mg tablets by mouth twice daily, day 1 to 28), associated to intravenous carboplatin (area under the curve (AUC) 5 over 30 to 60 minutes, every 28 days). Patients who will develop carboplatin hypersensitivity reaction (HSR) will follow a desensitization protocol, or alternatively will switch to cisplatin. Erythropoietic stimulating agent and myeloid growth factors are not permitted for cycle 1 of study treatment, and their use will be chosen by the treating physician, according to hospital policy.Treatment will be discontinued when any of the following events occurs: radiographic or clinical evidence of cancer progression; deterioration of health or intolerable toxicity; patient refusal. Before starting treatment, patients will be evaluated by medical history, physical examination, cell blood count (CBC), chemistry panel, Ca125, and either computed tomography or magnetic resonance imaging scan. The primary endpoint is to determine the overall response (OR) rate. Secondary endpoints include the assessment of duration of response, PFS, OS, toxicity events and QoL scores. When treatment will be discontinued, patients will receive a follow-up visit every 3 months

Study of the Combination Carboplatin Plus Celecoxib in Heavily Pre-treated Recurrent Ovarian Cancer Patients

Phase II Study of the Combination Carboplatin Plus Celecoxib in Heavily Pre-treated Recurrent Ovarian Cancer Patients

The tumor response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and duration of response, progression-free survival (PFS), overall survival (OS), toxicity assessment, and quality of life (QoL) measures with carboplatin-celcoxib in heavly pretreated recurrent ovarian cancer patients.

Serum levels of vascular endothelial growth factor (VEGF) and endostatin evaluated in a preliminary series of 11 patients at baseline and after 1 month of carboplatin-celecoxib

Catholic University of the Sacred Heart

Giovanni SCAMBIA-Department of Obstetrics and Gynecology-Catholic University of the Sacred Heart

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Arm A (Experimental arm).

* Nivolumab 3 mg/kg
* Ipilimumab 1 mg/kg

Arm B (Control arm). Pazopanib 800 mg/day

The combination of Nivolumab+Ipilimumab will be given to patients as follows:

* Nivolumab: 3 mg/kg IV over 30 minutes every 2 weeks for 4 cycles.
* Ipilimumab 1 mg/kg IV over 60 minutes every 6 weeks for 4 cycles. After completion of 4 courses with ipilimumab, patients continue receiving nivolumab IV at the dose of 480 mg Q4W in the absence of disease progression or unacceptable toxicity for a maximum of 18 months.

Nota Bene: A cycle is defined as a 6-weeks period.

The planned treatment period is 24 months

Nivolumab and Ipilimumab must be injected the same day every 6 weeks (Q6W). In case of toxicity, dose will be delayed, but will not be reduced.

Nivolumab and IPILIMUMAB

Treatment by pazopanib 800 mg/day per os, continuously during a maximum 24 months.

In case of toxicity, dose will be delayed and reduced.

Pazopanib Oral Tablet [Votrient]

Séverine METZGER

Mehdi BRAHMI

Justine GANTZER

Mehdi BRAHMI, Dr

Armelle DUFRESNE, Dr

Hélène VANACKER, Dr

Jean-Yves BLAY, Dr

Loïc CHAIGNEAU

Antoine Italiano, MD

Alice Hervieu, MD

Nicolas Penel, MD

François Bertucci, MD

Agnès Ducoulombier, MD

Camille Tlemsani, MD

Nicolas Isambert, MD

Christophe Perrin, MD

Thibaud Valentin, MD

Benjamin Verret, MD

This is a randomized open label study, with 2 arms treatments conducted in patients with metastatic or unresectable advanced sarcoma of rare subtype; previously treated by anthracycline-based regimen except for whom standard therapy does not exist or is not considered appropriate by the Investigator.

In the experimental arm, patients will receive the combination of Nivolumab + Ipilimumab for a maximum of 24 months, whereas in the control arm, patients will receive Pazopanib alone.

The purpose of the study is to know if the combination of nivolumab + ipilimumab can be more efficient than Pazopanib in terms of Progression-Free Survival.

This is a randomized open label, comparative, prospective, multicentre phase III study.

The patients who meet the eligibility criteria will be randomly assigned (1:1) into one of the following treatments groups:

* Experimental arm: Nivolumab + Ipilimumab (24 months maximum)
* Control arm: Pazopanib alone (24 months maximum)

A randomization procedure will be used to obtain a balanced distribution of stratifications factors:

* The number of previous lines of treatment in advanced/metastatic setting: ≤1 line or \>1 line (a treatment line is defined as a treatment initiation whatever the reason)
* The lymphocytes count at baseline: \<1 g/L or ≥1 g/L.

After their eligibility has been confirmed, patients will be treated with:

* The combination of Nivolumab + Ipilimumab for 4 cycles. After completion of 4 cycles with Ipilimumab, patients continue receiving nivolumab IV (480 mg Q4W) in the absence of disease progression or unacceptable toxicity. A cycle is defined as a 6-weeks period.
* Or Pazopanib until disease progression or unacceptable toxicity. The planned treatment duration in both arm is maximum 24 months.

After the completion of treatment, patients will be followed up within 30 days after the last study treatment administration. The survival and disease status will be updated for all patients at the time of the end of the study.

The overall end of the study will be the Last Patient Last Visit (LPLV), defined as the End Of Treatment (EOT) visit of the last active patient.

Efficacy of the Combination of Nivolumab and Ipilimumab as a Treatment in Patients With Sarcoma of Rare Subtype

A Randomised, Comparative, Prospective, Multicentre Study of the Efficacy of Nivolumab + Ipilimumab Versus Pazopanib Alone in Patients With Metastatic or Unresectable Advanced Sarcoma of Rare Subtype (RAR-Immune)

The Progression-Free Survival defined as the time from the date of randomisation to the date of first documented progression or death due to any cause. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment.

The Best Overall Response will be defined as the best among all overall responses during the trial.

The Objective Response Rate will be defined as the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) during the trial.

in the patients whose BOR is either CR or PR, the DOR will be defined as the time from the date of first documented tumour response to the date of first documented disease progression or death due to underlying cancer. Patients with no event at the time of the analysis will be censored.

The Time to Treatment Failure will be defined as the time from the date of randomisation to the date of permanent study treatments discontinuation (any cause, including disease progression, treatment toxicity, adverse event, start of any new anticancer therapy, withdrawal of consent and death). Patients without treatment failure at the time of the analysis will be censored at the date of last tumour

The Overall Survival will be defined as the time from the date of randomisation to the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.

The Quality of Life will be assessed using the EORTC QLQ-C30 questionnaire.

The Tolerance profile will be described through the incidence and severity of drug-related AEs according to the Common Terminology Criteria for Adverse Events (CTCAE) (v5.0)

Centre Leon Berard

Skin and Connective Tissue Diseases

Wounds and Injuries

Eye Diseases

Melanoma

Neoplasm Metastasis

Hyperthermia

Fever

Eye Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Ocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Temozolomide

Melphalan

Laparotomy

Ocular melanoma, or cancer of the eye, is a rare form of cancer that can spread to the liver. A tumor in the liver, because of its size or location, sometimes cannot be removed with surgery.

The purpose of this study is to determine whether chemotherapy delivered only to the liver, called isolated hepatic perfusion (IHP), followed by systemic (to the whole body) chemotherapy improves the ability to treat cancer.

Study participants must be 18 years or older and have ocular melanoma that has spread to the liver. Before enrolling in the study, they will undergo the following evaluations: a physical exam; x-rays; blood tests; electrocardiogram; computed tomography (CT) scan of the chest, abdomen and pelvis; and a magnetic resonance imaging (MRI) scan of the liver.

The study includes a 15-minute quality-of-life questionnaire. Participants will complete the questionnaire 7 times over a period of 2 years to help investigators gauge their health status and progress.

A laparotomy is done, which allows a surgeon to view the tumor in the liver through a small incision in the abdomen while the patient is under general anesthesia. Sometimes the tumor can spread outside the liver in a way that cannot be seen by pre-operative scans. When this happens, the participant is ineligible to continue in the study, since an important part of the treatment is given only to the liver.

If the laparotomy reveals that the participant is eligible for the remainder of the study, the participant will receive IHP treatment during the surgery. Plastic tubes called catheters are placed in the vein and artery that feed and drain the liver. This creates a separate blood supply for the liver alone. Heated chemotherapy is then given into the liver blood supply for one hour, while being carefully kept out of the rest of the body.

After recovering from the surgery, eligible participants will receive a systemic chemotherapy called temozolomide for up to one year. This chemotherapy is taken by mouth in capsule form.

Participants will be asked to return to NIH 10-11 times during the first year to evaluate their progress.

Patients with unresectable hepatic metastases secondary to ocular melanoma will undergo a 60 minute hyperthermic isolated hepatic perfusion with 1.5mg/kg melphalan followed by up to one year of oral temozolomide. Response to treatment, duration of response, patterns of failure, survival, and quality of life end-points will be followed.

A Phase II Study of Isolated Hepatic Perfusion (IHP) in Patients With Ocular Melanoma

A Phase II Study of Isolated Hepatic Perfusion (IHP) With Melphalan Followed by Temozolomide for Subjects With Unresectable Hepatic Metastases From Ocular Melanoma

National Cancer Institute (NCI)

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Paclitaxel

Albumin-Bound Paclitaxel

Abraxane (nab®paclitaxel) 125 milligrams per meter squared on days 1, 8 and 15 of a 28 day cycle

ABI-007

Alfredo Romano, MD

The purpose of this study is to evaluate the safety and efficacy of Abraxane (nab-paclitaxel) in subjects with previously treated metastatic colorectal cancer. Subjects will be placed into two separate cohorts based on their RAS mutation status.

ABI-007-COLO-001 is a Phase 2, single arm, open label, multicenter study to evaluate the efficacy and safety of Abraxane (nab-paclitaxel) given on days 1, 8 and 15 of a 28 day cycle in subjects with previously treated metastatic colorectal cancer. Subjects will be enrolled into cohorts by RAS mutation status (wildtype or mutated). Stage 1 in a given cohort will enroll 15 subjects in the Intention to Treat population and if more than 8 subjects have Progression Free Survival at the 8 week assessment, then Stage 2 will open in the respective cohort. Stage 2 will enroll an additional 28 subjects for a total of 43 subjects in each cohort. The study will be positive if more than 26 subjects with Progression Free Survival at the 8 week assessment are observed in 43 subjects per cohort. Interim analysis after Stage 1 did not meet protocol defined criteria to proceed to Stage 2. Patients currently enrolled will be followed for Progression Free Survival and until 28 days after last dose, secondary endpoints including overall survival will not be followed

Phase 2 Study With Abraxane (Nab®Paclitaxel) in Metastatic Colorectal Cancer

A SINGLE ARM PHASE 2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF Nab®-PACLITAXEL, IN SUBJECTS WITH PREVIOUSLY TREATED METASTATIC COLORECTAL CANCER

PFS was measured as time from the date of first dose to the date of disease progression according to RECIST 1.1 or death from any cause, whichever was earlier.

PFS rate was measured by Investigator Assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 from the start of study treatment to disease progression or death from any cause, whichever occurred first.

DCR was defined as the combined incidence of stable disease confirmed CR or PR and stable disease (SD) measured at the Week 8 assessment or later.

Overall Survival was the time from the first dose of study drug to patient death from any cause.

ORR was defined as the combined incidence of Complete Response (CR) and Partial Response (PR), confirmed no less than 4 weeks after the criteria for response were first met based on RECIST 1.1. Tumor responses were assessed every 2 cycles using RECIST 1.1 and defined as: • Complete response-disappearance of all target lesions • Partial response- At least a 30% decrease in the sum of diameters of target lesions from baseline • Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD) • Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.

Duration of response was defined as the time from the first tumor assessment when the confirmed CR/PR response criterion was met to the date of disease progression based on investigational assessment following RECIST 1.1.

A treatment emergent adverse events (TEAE) was defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. A TESAE is defined as any serious adverse event (SAE) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. Safety and Severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Lifethreatening; Grade 5-Fatal;

Celgene

nab®-paclitaxel 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.

RAS Wildtype: Nab®-Paclitaxel

RAS Mutated: Nab®-Paclitaxel

Total

Age, Continuous

Sex: Female, Male

Intent to Treat (ITT) Includes participants who met all eligibility criteria and received at least one dose of study drug.

Anne McClain, Senior Manager, Clinical Trial Disclosure

Per the Simon 2-stage design, only 30 participants from Stage 1 (the first 15 participants in the Intent to Treat (ITT) population from each cohort) were included. The ITT population was defined as those who received treatment and met all eligibility criteria; four ineligible participants were excluded based on the protocol deviations/violations

Progression Free Survival (PFS) Rate as Measured at Week 8

ITT Population defined as participants who received treatment and met all eligibility criteria

Percentage of Participants With Stable Disease for ≥ 8 Weeks, or Complete or Partial Response According to RECIST Version 1.1; Disease Control Rate (DCR)

The data from the primary efficacy endpoint met the stopping criteria defined by the Simon 2-stage design, which did not support further assessment of nab-paclitaxel as a monotherapy in the analysis of this group of participants. The study was stopped early and the analysis of overall survival was not performed.

Overall Survival

ITT population defined as participants who received treatment and met all eligibility criteria.

Overall Response Rate (ORR)

Abraxane (nab®-paclitaxel) 125 mg/m\^2 on days 1, 8 and 15 of every 28 day cycle until disease progression, unacceptable toxicity, or withdrawal of consent.

RAS Wildtype Abraxane (Nab®-Paclitaxel)

RAS Mutated Abraxane (Nab®-Paclitaxel)

The data from the primary efficacy endpoint met the stopping criteria defined by the Simon 2-stage design, which did not support further assessment of nab-paclitaxel as a monotherapy in the analysis of this group of participants. Duration of response was not analyzed as there were no responders observed in the study.

Duration of Response (DOR)

Any TEAE

≥1 or more related TEAE

≥1 TEAE with Grade 3-4

≥1 treatment related TEAE with Grade 3 or 4

≥1 or TEAE Grade 3 or higher

Safety population includes all participants who received at least one dose of study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Real-world Study for Patients With Advanced Hepatobiliary Tumors	NCT03892577	Objective Respo... Progression-fre... Overall Surviva... Disease Control... Duration of Res... Five-year Survi... Quality of Life	Precision oncol...	18 Years -	Peking Union Medical College Hospital
Study of the Combination Carboplatin Plus Celecoxib in Heavily Pre-treated Recurrent Ovarian Cancer Patients	NCT01124435	Ovarian Neoplas...	Carboplatin plu...	18 Years - 75 Years	Catholic University of the Sacred Heart
Efficacy of the Combination of Nivolumab and Ipilimumab as a Treatment in Patients With Sarcoma of Rare Subtype	NCT04741438	Sarcoma	Nivolumab and I... Pazopanib Oral ...	18 Years -	Centre Leon Berard
A Phase II Study of Isolated Hepatic Perfusion (IHP) in Patients With Ocular Melanoma	NCT00062933	Melanoma	Laparotomy	18 Years -	National Institutes of Health Clinical Center (CC)
Phase 2 Study With Abraxane (Nab®Paclitaxel) in Metastatic Colorectal Cancer	NCT02103062	Colorectal Neop...	ABI-007	18 Years -	Celgene
A Study to Evaluate Lenalidomide Combined With Dexamethasone in Relapsed or Refractory Diffuse Large B-Cell Lymphoma	NCT00474188	Diffuse Large B...	CC-5013 (lenali... dexamethasone	18 Years -	Celgene
A Phase II Study of Isolated Hepatic Perfusion (IHP) in Patients With Ocular Melanoma	NCT00062933	Melanoma	Laparotomy	18 Years -	National Institutes of Health Clinical Center (CC)
Efficacy of the Combination of Nivolumab and Ipilimumab as a Treatment in Patients With Sarcoma of Rare Subtype	NCT04741438	Sarcoma	Nivolumab and I... Pazopanib Oral ...	18 Years -	Centre Leon Berard
Efficacy of the Combination of Nivolumab and Ipilimumab as a Treatment in Patients With Sarcoma of Rare Subtype	NCT04741438	Sarcoma	Nivolumab and I... Pazopanib Oral ...	18 Years -	Centre Leon Berard

Spots Global Cancer Trial Database for duration of response