Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Rare Diseases

Neoplasm Metastasis

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Ramucirumab

Antimetabolites

Angiogenesis Inhibitors

Growth Inhibitors

Participants received 8 mg/kg ramucirumab plus 25 mg/square meter (mg/m²) cisplatin and 1000 mg/m² gemcitabine intravenously (IV) on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for ramucirumab therapy).

Participants received placebo (indistinguishable and equivalent volume to ramucirumab) plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Participants received 80 mg merestinib orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for merestinib therapy).

Participants received placebo (indistinguishable to merestinib) orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days. Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Merestinib

Placebo Oral

Placebo IV

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this study is to evaluate the efficacy and safety of ramucirumab or merestinib or placebo plus cisplatin and gemcitabine in participants with advanced or metastatic biliary tract cancer.

A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer

Randomized, Double-Blind, Phase 2 Study of Ramucirumab or Merestinib or Placebo Plus Cisplatin and Gemcitabine as First-Line Treatment in Patients With Advanced or Metastatic Biliary Tract Cancer

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

OS defined as the time from from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

ORR was the number of participants who achieve a best overall response of CR or PR divided by the total number of participants randomized to the corresponding treatment arm as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Disease Control Rate (DCR) was the number of participants who achieve a best overall response of CR, PR, or SD divided by the total number of participants randomized to the corresponding treatment arm as per RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

PK was determined by the minimum observed plasma concentration (Cmin). 1 Cycle (C) = 21 days (D).

PK was presented through graphical overlay comparison versus historic data. No numerical summary of data was intended or produced.

Number of participants with positive treatment emergent anti-ramucirumab antibodies (ADA) was summarized by treatment group.

FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72. The Trial Outcomes Index (TOI) is the sum of the PWB, FWB and Hep subscales with a scores range of 0 to 128. The Total FACT-Hep score was the sum of all questions with a scores range of 0 to 180.Total FACT-G score was the sum of the 27 questions in the PWB, SFWB, EWB and FWB with a scores range of 0 to 108. The FACT-Hep Symptoms Index with 8 key questions and scores range of 0 to 32 from the Hep Subscale. Higher score in sub-score or total score indicates better QOL and better health state. Participants were classified as "Improved" if they had positive change from baseline, "Worsened" if they had negative change from baseline, and "Stable" otherwise.

EQ-5D-5L is a 2-part questionnaire that assesses general health status for 'today'. The first part is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive the health state index scores using country-specific algorithms, with scores ranging from less than 0 (where zero is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). Index values were calculated using the US algorithm (-0.109 to 1). A higher score indicates better health state.

EQ-5D-5L is a 2-part questionnaire that assesses general health status 'today'. The second part is assessed using a VAS on which the patient rates their perceived health state, ranging from 0 millimeter (the worst health you can imagine) to 100 millimeter (the best health you can imagine).

Eli Lilly and Company

All randomized participants who received at least 1 dose of study drug.

Participants received 8 mg/kg ramucirumab plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for ramucirumab therapy).

8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine

Total

Age, Continuous

All randomized participants

All randomized participants who received at least 1 dose of study drug

All randomized participants and all randomized participants who received at least 1 dose of study drug to align gender specific adverse event numbers.

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Argentina

Hungary

United States

Czechia

United Kingdom

Russia

Spain

Austria

South Korea

Sweden

Turkey

Belgium

Taiwan

Denmark

Mexico

Australia

France

Germany

Region of Enrollment

Chief Medical Officer

Participants received placebo IV and placebo oral (indistinguishable and equivalent volume to ramucirumab and merestinib) plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).

Pooled Placebo

All randomized participants. Censored participants: 8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine = 29; 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine = 34; Pooled Placebo = 25. Pooling is done in the placebo arm (Pooled Placebo) from both arms (Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine and Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine) for analysis purpose and combined as pre-specified in protocol.

Progression Free Survival (PFS)

Overall Survival (OS)

All randomized participants. Pooling is done in the placebo arm (Pooled Placebo) from both arms (Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine and Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine) for analysis purpose and combined as pre-specified in protocol.

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

Cycle 1 Day 8 (Week 1)

Cycle 2 Day 1 (Week 3)

Cycle 3 Day 1 (Week 6)

Cycle 4 Day 1 (Week 9)

Cycle 5 Day 1 (Week 12)

Cycle 7 Day 1 (Week 18)

Cycle 9 Day 1 (Week 24)

Cycle 13 Day 1 (Week 36)

All participants who received at least one dose of study drug and had evaluable PK data. As per protocol, Cmin of merestinib was not measured.

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Zero participants were analyzed as no data collected for summary analysis.

PK: Plasma Concentration of Merestinib

All randomized participants who received at least 1 dose of study drug with both baseline and at least one post baseline ADA assessments.

Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

FACT-Hep

All randomized participants who received at least 1 dose of study drug with baseline and one post-baseline FACT-Hep Questionnaire.

Change From Baseline in Functional Assessment of Cancer Therapy Hepatobiliary Questionnaire (FACT-Hep)

All randomized participants who received at least one dose of study drug with baseline and post-baseline EQ-5D 5L data.

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score

Change From Baseline in Participant-Reported EQ-5D-5L Visual Analog Scale (VAS) Score

Overall Study

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Lenvatinib

Oxaliplatin

Protein Kinase Inhibitors

Enzyme Inhibitors

Toripalimab plus lenvatinib and GEMOX (Gemcitabine hydrochloride and Oxaliplatin for injection ) or GC (Gemcitabine hydrochloride and Cisplatin)

Toripalimab plus lenvatinib placebo and GEMOX (Gemcitabine hydrochloride and Oxaliplatin for injection ) or GC (Gemcitabine hydrochloride and Cisplatin)

Toripalimab placebo plus lenvatinib placebo and GEMOX (Gemcitabine hydrochloride and Oxaliplatin for injection ) or GC (Gemcitabine hydrochloride and Cisplatin)

240 mg IV on day 1 of each 21-day treatment cycle (Q3W) for up to 35 treatment cycles

Toripalimab

Lenvatinib mesylate capsules

Placebo IV on day 1 of each 21-day treatment cycle (Q3W) for up to 35 treatment cycles

Oral placebo

85 mg/m2 IV, on day 1 of each 21-day treatment cycle (Q3W) up to 8 cycles

Oxaliplatin for injection

1 g/m2 IV, on day 1 and day8 of each 21-day treatment cycle (Q3W) up to 8 cycles

Gemcitabine hydrochloride

25 mg/m2 IV, on day 1 and day8 of each 21-day treatment cycle (Q3W) up to 8 cycles

Jiazheng Yan

Beibei Fei

Jian Zhou, doctor

This is a Phase III, prospective, randomized, three-arm, double-blind, placebo-controlled, international multicenter study to evaluate the efficacy and safety of toripalimab in combination with lenvatinib and gemcitabine-based chemotherapy compared with gemcitabine-based chemotherapy as first-line treatment for unresectable advanced ICC.

This study will enroll approximately 480 patients with unresectable advanced ICC who have received no prior systemic therapy. Patients who meet the requirements will be randomly assigned to Treatment Arm A: Toripalimab, lenvatinib, and gemcitabine-based chemotherapy or Treatment Arm B: Toripalimab, oral placebo, and gemcitabine-based chemotherapy or Treatment Arm C: Intravenous placebo, oral placebo, and gemcitabine-based chemotherapy.

All patients will receive standard chemotherapy (GEMOX or GC per Investigator decision) for a maximum of 8 cycles. After the completion of standard chemotherapy, all patients continue to receive maintenance therapy with toripalimab injection or its placebo in combination with lenvatinib mesylate capsule or its placebo until unacceptable toxicity, confirmed disease progression and loss of clinical benefit as determined by the investigators, start of new anti-cancer therapy, death, other conditions requiring termination of study treatment, or the patient meets the criteria for study withdrawal, whichever occurs first.

In the absence of unacceptable toxicity, patients who meet criteria for unconfirmed disease progression per RECIST v1.1 while receiving toripalimab, lenvatinib, or their placebos will be permitted to continue treatment if their clinical status or symptoms are stable or improved (as determined by the investigators) or until loss of clinical benefit. Patients with confirmed disease progression should discontinue toripalimab, lenvatinib, or their placebos.

Tumor assessments will be performed at screening and during the study treatment per protocol. In the absence of progression, tumor assessments will continue as scheduled, regardless of whether study treatment ends, until confirmed disease progression or other criteria for study withdrawal are met, whichever occurs first. Patients who meet RECIST v1.1 criteria for progression should undergo tumor assessments as scheduled if clinical benefits of continuing study treatment are determined by investigators until progression is confirmed per iRECIST (iCPD), or the criteria for study withdrawal are met, whichever occurs first.

Computerized tomography (CT)/magnetic resonance imaging (MRI) scans for efficacy evaluation will be performed at baseline, every 6 weeks (Q6W) in the first year (52 weeks), and every 9 weeks (Q9W) in the second year (after week 52).

All AEs and concomitant medications during the study will be recorded. An end-of-treatment (EOT) visit will be performed within 30 days after the last dose of study treatment or termination of study treatment is confirmed by the investigator. After the EOT visit, follow-up for survival (telephone visit is allowed) will be conducted and AEs and subsequent anti-cancer therapy will be collected.

Toripalimab Plus Lenvatinib and Gemcitabine-based Chemotherapy in 1L Treatment of Advanced ICC: a Phase III Study

A Phase III, Randomized, Three-arm, Double-blind, Placebo-controlled, International Multi-center Study to Evaluate the Efficacy and Safety of Toripalimab in Combination With Lenvatinib and Gemcitabine-based Chemotherapy Compared With Gemcitabine-based Chemotherapy as First-line Treatment in Patients With Unresectable Advanced Intrahepatic Cholangiocarcinoma (ICC)

1-year and 2-year OS rates between Arm A and Arm C

1-year and 2-year OS rates between Arm B and Arm C

To evaluate incidence, severity and outcome of adverse events (AE), immune-related adverse events (irAE) and serious adverse events (SAE)

OS is defined as the time from randomization to death due to any cause. Overall survival will be compared between Arm A and Arm C

OS is defined as the time from randomization to death due to any cause. Overall survival will be compared between Arm B and Arm C

Investigator-determined progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) in Arm A compared with Arm C (PFS A vs. C);

Investigator-determined PFS according to RECIST v1.1 in Arm B compared with Arm C (PFS B vs. C);

Investigator-determined objective response rate (ORR) according to RECIST v1.1 in Arm A compared with Arm C (ORR A vs. C)

Investigator-determined ORR according to RECIST v1.1 in Arm B compared with Arm C (ORR B vs. C)

Shanghai Junshi Bioscience Co., Ltd.

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Immune System Diseases

Arthritis

Necrosis

Arthritis, Rheumatoid

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Autoimmune Diseases

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Inflammatory Agents

Methotrexate

Tumor Necrosis Factor Inhibitors

60 mg subcutaneously (sc) at Weeks 0, 2, 4 6, 8, and 10

CDP6038

8 mg/kg intravenously (iv) at Weeks 0, 4 and 8

Tocilizumab (Actemra or RoActemra)

0.9% Sodium chloride for injection at Weeks 0, 2, 4 6, 8, and 10

Placebo sc

0.9% Sodium chloride for injection at Weeks 2, 6 and 10

0.9% Sodium chloride for injection at Weeks 0, 4 and 8

Placebo iv

UCB Clinical Trial Call Center

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of CDP6038 treatment in adult subjects with active rheumatoid arthritis who have had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapy.

CDP6038 is a protein (antibody) that blocks interleukin-6 (IL-6), a substance involved in the inflammation associated with rheumatoid arthritis. This is a multicenter, 12-week, randomized, double-blind, placebo- and active- controlled study comparing several doses and dosage regimens (every 2 weeks and every 4 weeks) of CDP6038 to placebo and tocilizumab in patients with active rheumatoid arthritis who have had an unsuccessful response to methotrexate and previous anti-TNF therapy. The study will test if CDP6038 is more efficacious than placebo in reducing the signs and symptoms of rheumatoid arthritis at 12 weeks while maintaining an adequate safety profile. In order to maintain the study blinding all subjects will be given a subcutaneous (sc) injection (under the skin) every 2 weeks, as well as an intravenous (iv) infusion every 4 weeks. In addition subjects must remain on stable weekly doses of methotrexate. Assessments during the study include evaluations of joint pain and swelling, laboratory blood and urine tests, physical examinations, vital signs, electrocardiograms, and questionnaires. Subjects who complete the 12-week study will be eligible to enroll in a long-term extension study receiving CDP6038.

Efficacy and Safety of CDP6038 in Patients With Rheumatoid Arthritis With an Unsuccessful Response to Anti-Tumor Necrosis Factor (Anti-TNF) Therapy

Randomized, Double-blind, Placebo-controlled, Dose Ranging Study With an Active Comparator to Evaluate the Efficacy and Safety of CDP6038 Administered Subcutaneously for 12 Weeks to Subjects With Rheumatoid Arthritis Having Previously Failed TNF-blocker Therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer	NCT02711553	Biliary Tract C... Metastatic Canc... Advanced Cancer	Ramucirumab Merestinib Cisplatin Gemcitabine Placebo Oral Placebo IV	18 Years -	Eli Lilly and Company
Toripalimab Plus Lenvatinib and Gemcitabine-based Chemotherapy in 1L Treatment of Advanced ICC: a Phase III Study	NCT05342194	Intrahepatic Ch...	Toripalimab Lenvatinib mesy... Placebo IV Oral placebo Oxaliplatin for... Gemcitabine hyd... Cisplatin	18 Years - 75 Years	Shanghai Junshi Bioscience Co., Ltd.
Efficacy and Safety of CDP6038 in Patients With Rheumatoid Arthritis With an Unsuccessful Response to Anti-Tumor Necrosis Factor (Anti-TNF) Therapy	NCT01242488	Rheumatoid Arth...	CDP6038 CDP6038 CDP6038 Tocilizumab (Ac... CDP6038 CDP6038 CDP6038 Placebo sc Placebo sc Placebo iv	18 Years -	UCB Pharma
A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer	NCT02711553	Biliary Tract C... Metastatic Canc... Advanced Cancer	Ramucirumab Merestinib Cisplatin Gemcitabine Placebo Oral Placebo IV	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for placebo iv

Every month we try and update this database with for placebo iv cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for placebo iv

Every month we try and update this database with for placebo iv cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for placebo iv cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.