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

Skin and Connective Tissue Diseases

Blood and Lymph Conditions

Breast Neoplasms

Neutropenia

Agranulocytosis

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Granulocytopenia

Doxorubicin

Liposomal doxorubicin

Docetaxel

Lenograstim

Participants will receive balugrastim low dose administered by subcutaneous (SC) injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Participants will receive balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Participants will receive balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Participants will receive pegfilgrastim 6 mg administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Balugrastim (Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor) will be administered per dose and schedule specified in the arm description.

Balugrastim

Pegfilgrastim will be administered per dose and schedule specified in the arm description.

Pegfilgrastim

The chemotherapy regimen consisting of doxorubicin 60 mg/square meter (m\^2) and docetaxel 75 mg/m\^2 will be administered sequentially by intravenous (IV) infusion on Day 1 of treatment for up to four 21-day cycles.

Chemotherapy Regimen

Teva Medical Expert, MD

Determination of the effect of balugrastim on the duration and severity of severe neutropenia.

Balugrastim (Neugranin) in Breast Cancer Participants Receiving Doxorubicin/Docetaxel

A Randomized Study of Subcutaneously Administered Neugranin (Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor) or Pegfilgrastim in Subjects With Breast Cancer Receiving Myelosuppressive Chemotherapy (Doxorubicin/Docetaxel)

Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<0.5 x 10\^9/liter \[L\]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle.

Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and oral temperature ≥38.2 degrees celsius (°C) occurring on the same day. Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.

Severe neutropenia was defined as Grade 4 neutropenia (ANC \<0.5 x 10\^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle.

Time to ANC recovery was defined as the time from the nadir ANC to an ANC ≥1.5 x 10\^9/L and was calculated for participants with ANC \<1.5 x 10\^9/L after the beginning of a chemotherapy cycle. Time to ANC recovery was calculated by cycle as the number of days from the nadir (the lowest ANC during a chemotherapy cycle) until a participant reached an ANC \>1.5 x 10\^9/L.

Teva Branded Pharmaceutical Products R&D, Inc.

mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Per planned analysis, adverse events are reported combined for pilot and main phase.

Participants received balugrastim low dose administered by subcutaneous (SC) injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Balugrastim Low Dose

Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Balugrastim Medium Dose

Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Balugrastim High Dose

Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days).

Pilot Phase: Balugrastim Low Dose

Pilot Phase: Balugrastim Medium Dose

Pilot Phase: Balugrastim High Dose

Pilot Phase: Pegfilgrastim

Main Phase: Balugrastim Medium Dose

Main Phase: Balugrastim High Dose

Main Phase: Pegfilgrastim

Race

Race/Ethnicity, Customized

Modified intent-to-treat (mITT) population included all participants who were randomized into the study and received at least 1 dose of assigned study drug.

Director, Clinical Research

mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Duration of Severe Neutropenia in Cycle 1

mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug.

Number of Participants With Febrile Neutropenia

Cycle 2

Cycle 3

Cycle 4

mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified cycle.

Duration of Severe Neutropenia in Cycles 2, 3, and 4

Cycle 1

Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4

Pilot Phase

Main Phase

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Anti-Infective Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Hormones

Ketoconazole

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Ketoconazole 200mg PO TID + Hydrocortisone 20mg PO Qam, 10mg PO Qpm

Ketoconazole is taken three times a day by mouth.

Hydrocortisone is taken by mouth 20 mg every morning and 10 mg every evening.

Primo N Lara Jr., MD

The purpose of this study is to test the safety of ketoconazole and how well it works after chemotherapy has been used. Ketoconazole at lower doses has been used for fungal infections however has not yet been approved by the Food and Drug Administration for use in prostate cancer. Ketoconazole has been used for many years at high doses for prostate cancer, and this study will be to look at use of lower dose ketoconazole after someone has received chemotherapy. Ketoconazole works by halting the production of steroids in your body, including testosterone, and is thought to work directly on prostate cancer cells in published lab studies.

The aim of the study is to research the response of low dose ketoconazole in hormone refractory prostate cancer (HRPC) patients who have already undergone chemotherapy as part of their prostate cancer treatment. The hypothesis of the study is that HRPC patients who have been previously treated with chemotherapy will demonstrate objective PSA response rates to low dose ketoconazole, comparable to historical response rates reported in chemotherapy-naïve patients. This is a single arm trial, with all participants given ketoconazole 200mg TID, along with hydrocortisone given at 20mg in the morning, 10mg at night daily. Each cycle will consist of 28 days. The subject's study participation will continue until subject experiences disease progression, unacceptable toxicities, withdraws consent from the study or dies.

Use of Low Dose Ketoconazole in Prostate Cancer That Does Not Respond to Hormone Therapy and Prior Chemotherapy

Assessing PSA Response in Low Dose Ketoconazole in Hormone Refractory Prostate Cancer Patients Who Have Failed at Least One Prior Systemic Chemotherapy Regimen

Percentage of patients who achieved a clinically significant decline in Prostate Specific Antigen (PSA) after initiation of ketoconazole therapy, defined as a \>=50% decrease in PSA.

Response Evaluation Criteria In Solid Tumors (RECIST) radiographic criteria for progression

University of California, Davis

Ketoconazole 200mg PO TID + Hydrocortisone 20mg PO Qam, 10mg PO Qpm

Ketoconazole: Ketoconazole is taken three times a day by mouth.

Analyst

Prostate Specific Antigen (PSA) Response (>50% Reduction From Baseline)

PSA Response (>30% From Baseline)

Progression Free Survival

Duration of Stable Disease

Ketoconazole 200mg PO (by mouth) TID (three times a day) + Hydrocortisone 20mg PO Qam (every morning), 10mg PO Qpm (every evening)

Ketoconazole: Ketoconazole is taken three times a day by mouth.

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.
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.
Balugrastim (Neugranin) in Breast Cancer Participants Receiving Doxorubicin/Docetaxel	NCT00837265	Chemotherapy-in...	Balugrastim Pegfilgrastim Chemotherapy Re...	18 Years -	Teva Branded Pharmaceutical Products R&D, 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.
Use of Low Dose Ketoconazole in Prostate Cancer That Does Not Respond to Hormone Therapy and Prior Chemotherapy	NCT00895310	Prostate Cancer	Ketoconazole Hydrocortisone	18 Years -	University of California, Davis

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