Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Cholangiocarcinoma

Klatskin Tumor

Carcinoma, Ductal

Bile Duct Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Central Nervous System Depressants

Gemcitabine

Cisplatin

Dihematoporphyrin Ether

Trioxsalen

Hematoporphyrin Derivative

Ether

Hematoporphyrins

Antimetabolites

Photosensitizing Agents

Photodynamic therapy (PDT) involves the i.v. injection of Photofrin followed by the illumination of the tumor using a fiber optic device. Two days after the injection, a laser light (180 J/cm(2)) will be applied to the tumor. A second light application will be given 96-120 hours after Photofrin injection if PDT could not initially be performed on all sides of the tumor. Post illumination, all patients will undergo stenting as part of standard medical care procedure. Up to 3 additional courses of PDT using a light dose of 120 J/cm(2) may be given at 3-month intervals. Standard Medical Care (SMC) is defined as stenting procedure plus chemotherapy regimen.

Standard Medical Care (SMC) is defined as stenting procedure plus chemotherapy regimen. The chemotherapy regimen will comprise gemcitabine (1 000 mg/m(2)) followed by cisplatin (25 mg/m(2)), each administered on days 1 and 8 every 3 weeks (21 day-cycle) for four cycles. An additional 12 weeks of the same chemotherapy regimen may be administered if there is no disease progression or intolerable toxicity.

Photodynamic therapy (PDT) involves the i.v. injection of Photofrin (2 mg/kg) followed by the illumination of the tumor using a fiber optic device during an endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). Two days after the injection, a laser light (180 J/cm(2)) will be applied to the tumor. A second light application will be given 96-120 hours after Photofrin injection if PDT could not initially be performed on all sides of the tumor. Post illumination, all patients will undergo stenting as part of standard medical care procedure. Up to 3 additional courses of PDT using a light dose of 120 J/cm(2) may be given at 3-month intervals.

Photodynamic therapy-Photofrin

As per standard medical procedures, stenting procedure consists in the placement of stents above the main tumors of the right and left hepatic bile ducts via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) when the ERCP approach has been unsuccessful.

Stenting procedure

The regimen will comprise gemcitabine (1 000 mg/m(2)) followed by cisplatin (25 mg/m(2)), each administered on days 1 and 8 every 3 weeks (21 day-cycle) for four cycles. An additional 12 weeks of the same chemotherapy regimen may be administered if there is no disease progression or intolerable toxicity.

Chemotherapy regimen

Michel Kahaleh, MD

Photodynamic therapy (PDT) is a combination of a drug, porfimer sodium (Photofrin), which is activated by a light from a laser that emits no heat. This technique works to allow the medical doctor to specifically target and destroy abnormal or cancer cells while limiting damage to surrounding healthy tissue. The activation of the drug is done by lighting the abnormal areas using a fiber optic device (very fine fiber like a fishing line that permits light transmission) inserted into a flexible tube with a light called cholangioscope for the bile duct. The light will activate the porfimer sodium concentrated in the abnormal tissue, leading to its destruction.

This research study will evaluate the efficacy and safety of PDT with porfimer sodium administered with Standard Medical Care (SMC) compared to SMC alone on the overall survival time of patients with non-operable advanced cholangiocarcinoma, a rare cancer of the bile ducts. It will involve 200 patients across North America and Europe. Other countries may participate if needed. Participation will last at least 18 months.

Photodynamic therapy (PDT) is a combination of a drug, porfimer sodium (Photofrin), which is activated by a light from a laser that emits no heat. This technique works to allow the medical doctor to specifically target and destroy abnormal or cancer cells while limiting damage to surrounding healthy tissue. The activation of the drug is done by lighting the abnormal areas using a fiber optic device (very fine fiber like a fishing line that permits light transmission) inserted into a flexible tube with a light called cholangioscope for the bile duct. The light will activate the porfimer sodium concentrated in the abnormal tissue, leading to its destruction.

Cholangiocarcinoma (CCA) is defined as primary malignant tumors of the bile ducts. The exact etiology remains unknown. These cancerous tumors block the bile flow and can be intrahepatic (IH) or extrahepatic (EH). The distinction between IH- and EH-CCA has become increasingly important, as the epidemiological features (i.e., incidence and risk factors), the biologic and pathologic characteristics and the clinical course are largely different. Unfortunately, most subjects are found to have metastases or unresectable disease at the time of diagnosis. Median survival for subjects with unresectable perihilar-CCA varies between five and eight months. The one-year survival is 50%, with 20% surviving at two years and 10% at three years. Unresected CCA is a rapidly fatal process with cholangitis being a significant cause of morbidity and mortality in these subjects.

This study was designed to confirm the efficacy of PHOPDT + standard medical care (SMC) defined as stents plus gemcitabine/cisplatin chemotherapy regimen on the overall survival of subjects with unresectable cholestasis perihilar Bismuth type III or IV - tumor TNM stage III or IVa CCA.

Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)

Multicenter, Open-label, Randomized, Controlled Phase III Clinical Study of the Efficacy and Safety of Photodynamic Therapy Using Porfimer Sodium for Injection as Treatment for Unresectable Advanced Perihilar Cholangiocarcinoma

The study was prematurely discontinued meaning only descriptive analyses are possible. It is not feasible to share this sort of data.

Time from the date of randomization until the date of death or the last date the subject was known to be alive

From the date of randomization until the date of first documented bilirubin response

From the start of the treatment until disease progression or recurrence the RECIST 1.1 criteria are applied (Response Evaluation Criteria in Solid Tumors)

From the date of first documented response until the date that tumor progression was assessed

The Karnofsky Performance Scale scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is normal activity with effort and some signs or symptoms of disease.

The Karnofsky Performance Scale (KPS) scores range from 0% to 100%. The lower the Karnofsky score, the worse likelihood of survival. A score of 100% means there are no complaints and no evidence of disease. A score of 80% means there is normal activity with effort and some signs or symptoms of disease. A score of 0% means death.

Final European Organisation for Research and Treatment of Cancer (EORTC) scores for multi-item scales and single-item measures will range from 0 to 100. This questionnaire assesses the quality of life of cancer patients. A high score represents a high/healthy level of functioning, basically a high Quality of Life.

Concordia Laboratories Inc.

The SMC alone group enrolled 13 subjects but only 10 were treated thus there were only 10 subjects at risk for adverse events.

Photodynamic therapy (PDT) involved the i.v. injection of Photofrin (2 mg/kg) followed by the illumination of the tumor using a fiber optic device. Two days after the injection, a laser light (180 J/cm(2)) was applied to the tumor. A second light application was given 96-120 hours after Photofrin injection if PDT could not initially be performed on all sides of the tumor. Post illumination, all patients underwent stenting. Up to 3 additional courses of PDT using a light dose of 120 J/cm(2) could be given at 3-month intervals.

As per SMC, stenting procedure consisted of the placement of stents above the main tumors of the right and left hepatic bile ducts. The chemotherapy regimen comprised gemcitabine (1 000 mg/m(2)) followed by cisplatin (25 mg/m(2)), each administered on days 1 and 8 every 3 weeks (21 day-cycle) for four cycles. An additional 12 weeks of the same chemotherapy regimen could be administered if there was no disease progression or intolerable toxicity.

Photodynamic Therapy-Photofrin Plus SMC

Standard Medical Care (SMC) was defined as stenting procedure plus chemotherapy regimen. The chemotherapy regimen comprised gemcitabine (1 000 mg/m(2)) followed by cisplatin (25 mg/m(2)), each administered on days 1 and 8 every 3 weeks (21 day-cycle) for four cycles. An additional 12 weeks of the same chemotherapy regimen could be administered if there was no disease progression or intolerable toxicity. As per SMC, stenting procedure consisted of the placement of stents above the main tumors of the right and left hepatic bile ducts.

Standard Medical Care (SMC)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

South Korea

United States

Germany

Region of Enrollment

This study was prematurely terminated due to low accrual. Consequently, there was insufficient data to allow statistical analysis. Only descriptive statistics are presented for the primary endpoint, overall survival time.

Dr. Michelle Depot

All participants randomized (intent-to-treat population)

Overall Survival Time

Time-to-bilirubin Response

Due to the premature termination of the study, there was insufficient data to allow statistical analysis.

Best Overall Tumor Response as Measured by the RECIST 1.1 Criteria (Response Evaluation Criteria in Solid Tumors)

Time-to-tumor Progression

At Day 7, all 15 subjects in the PDT +SMC group were analysed and 9/13 in the SMC Alone group were analysed.

Change From Baseline on Karnofsky Performance Scale (KPS)

At 4 weeks, 12 subjects in the PDT +SMC group were analysed and 9 in the SMC Alone group were analysed.

Change From Baseline in Performance Status on the Karnofsky Performance Scale (KPS)

At 13 weeks, 8 subjects in the PDT +SMC group were analysed and 8 in the SMC Alone group were analysed. Due to the premature termination of the study, there was insufficient data to allow statistical analysis.

At 16 weeks, 9 subjects in the PDT +SMC group were analysed and 9 in the SMC Alone group were analysed. Due to the premature termination of the study, there was insufficient data to allow statistical analysis.

At 29 weeks, 6 subjects in the PDT +SMC group were analysed and 5 in the SMC Alone group were analysed. Due to the premature termination of the study, there was insufficient data to allow statistical analysis.

At 41 weeks, 2 subjects in the PDT +SMC group were analysed and 1 in the SMC Alone group was analysed. Due to the premature termination of the study, there was insufficient data to allow statistical analysis.

At 54 weeks, only 1 subject in each group was measured. Due to the premature termination of the study, there was insufficient data to allow statistical analysis.

Change From Baseline in Health-related Quality of Life on the 4- and 7-point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)

Change From Baseline in Health-related Quality of Life on the 4- and 7-point EORTC QLQ-C30

Overall Study

Blood and Lymph Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Symptoms and General Pathology

Anemia

Fanconi Syndrome

Fanconi Anemia

Biliary Tract Neoplasms

Syndrome

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Anemia, Hypoplastic, Congenital

Anemia, Aplastic

Hematologic Diseases

Bone Marrow Failure Disorders

Pancytopenia

Congenital Bone Marrow Failure Syndromes

Bone Marrow Diseases

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Renal Tubular Transport, Inborn Errors

Kidney Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Biliary Tract Cancer

Congenital Aplastic Anemia

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive olaparib PO BID on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI throughout the trial, and collection of blood and tissue samples on study.

Undergo collection of blood and tissue samples

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Clinical Trials Referral Office

Daniel H. Ahn, MD

Clinical Trials Referrals Office

Amit Mahipal

Angemael Syldor

Ghassan K. Abou-Alfa

Charles Stava

Milind Javle

Daniel H Ahn

This phase II trial studies how well olaparib works in treating patients with biliary tract cancer that has spread to other places in the body (metastatic) and with aberrant DNA repair gene mutations. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the efficacy (progression free survival \[PFS\] rate at first scan) of olaparib monotherapy in advanced biliary tract cancer (BTC) with mutations in deoxyribonucleic acid (DNA) repair genes.

SECONDARY OBJECTIVES:

I. To determine the overall survival of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib.

II. To determine the progression free survival of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib.

III. To determine the objective response of patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib.

IV. To assess the duration of response for patients with advanced biliary tract cancer with mutations in DNA repair genes treated with olaparib who experience an objective response.

V. To assess the frequency and severity of adverse events in advanced biliary tract cancer patients treated with olaparib.

CORRELATIVE RESEARCH OBJECTIVES:

I. Determine the prevalence of mutations including those targeting DNA repair pathways.

II. Identify mutational signatures associated with pathogenic process in advanced biliary tract cancer samples.

III. Correlate the presence of mutations and mutational signatures linked to mutations in DNA repair genes and homologous recombinant repair with clinical responses to olaparib.

IV. To evaluate putative biomarkers related to:

Iva. De novo sensitivity. IVb. Tumor evolution and resistance, to PARP inhibition from olaparib in BTC.

OUTLINE:

Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) throughout the trial, and collection of blood and tissue samples on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 3 years.

Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations

A Phase II Study of Olaparib in Patients With Advanced Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations

Will determine the prevalence of mutations including those targeting DNA repair pathways.

Will identify mutational signatures associated with pathogenic process in advanced biliary tract cancer samples. Genomic analyses will be performed on mandatory blood samples collected from patients at the start of therapy, every 8 weeks, and at progression.

Will correlate the presence of mutations and mutational signatures linked to mutations in DNA repair/HRR with clinical responses.

Will evaluate putative biomarkers related to: (a) de novo sensitivity and (b) tumor evolution and resistance, to PARP inhibition in biliary tract cancer.

related to: (a) de novo sensitivity and (b) tumor evolution and resistance, to PARP inhibition in BTC.

A patient is defined as a success if the patient is progression-free and alive at the first disease evaluation scan. Disease status will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria. The PFS rate will be calculated as the proportion of evaluable patients who are progression-free and alive at the first disease assessment scan. The final PFS rate point estimate and corresponding 95% confidence interval (CIs) will be reported according to the method of Clopper-Pearson.

Patients who are still alive at the time of analysis will be censored at the time of their last study assessment (if still actively on the study) or at the date, the patient was last known to be alive (if in survival follow-up). OS will be estimated using the Kaplan-Meier method. The median OS and corresponding 95% confidence interval (by Brookmeyer and Crowley) will be reported.

Progression free survival is defined as the time from study registration to disease progression or death, whichever occurs first. Disease progression will be determined based on RECIST 1.1 criteria. Patients who do not experience disease progression or death while on the protocol will be censored at their last disease assessment date. PFS will be estimated using the Kaplan-Meier method. Median PFS and corresponding 95% CIs (by Brookmeyer and Crowley) will be reported.

Objective response (unconfirmed) is defined as achieving a complete or partial response while on treatment. The objective response rate (ORR) will be calculated as the proportion of evaluable patients who achieve an objective response. Disease status will be assessed using RECIST v1.1 criteria. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Will be defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete response or partial response to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier. The median DoR and corresponding 95% confidence interval will be reported.

Adverse events by patients will be summarized by frequencies and severity using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The proportion of patients who experience at least one grade 3+ adverse event (regardless of attribution) will be reported.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

Surufatinib: 250mg , po,qd, d1-d21, every 3 weeks for a treatment cycle. Cardonilimab: 10mg/kg, iv, d1, every 3 weeks for a treatment cycle

Surufatinib: 250mg , po,qd, d1-d21, every 3 weeks for a treatment cycle. Cadonilimab: 10mg/kg, iv, d1, every 3 weeks for a treatment cycle

surufatinib plus cadonilimab

Jieer Ying, M.D.

Jieer Ying, Doctor

This is an open-label, single-arm, multicenter Phase II clinical study to evaluate the efficacy and safety of surufatinib combined with cardanilimab in second-line treatment of patients with inoperable or metastatic bile duct adenocarcinoma

This is an open-label, single-arm, multicenter Phase II clinical trial. It is planned to enroll patients with inoperable or metastatic bile duct adenocarcinoma who have progressed through first-line chemotherapy combined with immunotherapy in several hospitals across the country to evaluate the efficacy and safety of second-line treatment with surufatinib Combination With Cadonilimab.

Surufatinib Plus Cadonilimab in Patients With Unresectable or Metastatic Bile Duct Adenocarcinoma

An Open-label, Single-arm, Multicenter, Phase II Clinical Study of Surufatinib Plus Cadonilimab as Second-line Therapy in Patients With Unresectable or Metastatic Bile Duct Adenocarcinoma

Refers to the date from the date of admission to the date of the first progression of disease or death of any cause, using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

The time interval between the start date of study drug and the date of death (any cause)

The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)

Percentage of confirmed cases including complete remission (CR), partial remission (PR) and disease stability (SD) among patients with evaluable efficacy

Categorized according to NCI Common Toxicity Criteria version 5.0. Summarized in terms of type, severity (grade 1-5), and dose level in tabular format.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)	NCT02082522	Hilar Cholangio...	Photodynamic th... Stenting proced... Chemotherapy re...	18 Years -	Concordia Laboratories Inc.
Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations	NCT04042831	Bile Duct Adeno... Fanconi Anemia ... Metastatic Bile... PTEN Gene Delet...	Biospecimen Col... Computed Tomogr... Magnetic Resona... Olaparib	18 Years -	Academic and Community Cancer Research United
Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)	NCT02082522	Hilar Cholangio...	Photodynamic th... Stenting proced... Chemotherapy re...	18 Years -	Concordia Laboratories Inc.
Efficacy and Safety Study of PDT Using Photofrin in Unresectable Advanced Perihilar Cholangiocarcinoma (OPUS)	NCT02082522	Hilar Cholangio...	Photodynamic th... Stenting proced... Chemotherapy re...	18 Years -	Concordia Laboratories Inc.
Surufatinib Plus Cadonilimab in Patients With Unresectable or Metastatic Bile Duct Adenocarcinoma	NCT06092645	Bile Duct Adeno...	surufatinib plu...	18 Years -	Zhejiang Cancer Hospital

Spots Global Cancer Trial Database for bile duct adenocarcinoma