Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

Antibodies

Capecitabine

Cetuximab

Immunoglobulins

Mitogens

Antimetabolites

Antineoplastic Agents, Immunological

Deirdre Cohen, MD

This is a Phase II, open label, non-randomized study in subjects with histologically confirmed diagnosis of advanced KRAS wild type adenocarcinoma of the colon or rectum, who have not received prior chemotherapy for metastatic disease.

The current treatment options for metastatic colon cancer are in need of further improvement. The three-drug combination of oxaliplatin with 5-FU/LV (fluorouracil/leucovorin) in the second-line treatment of metastatic colorectal cancer have shown a significant increase in response rate compared to 5-FU/LV alone. Oxaliplatin has recently been FDA-approved for this indication and is now a standard first-line agent in combination with a fluoropyrimidine. Cetuximab, a chimeric monoclonal antibody against the growth factor receptor, has shown activity with and without irinotecan in subjects with colorectal cancer refractory to irinotecan alone. Cetuximab has also been shown to be safe and effective when administered with infusional 5-FU/folinic acid plus irinotecan. These results suggest that the addition of cetuximab to fluoropyrimidine/oxaliplatin-based regimen in the 1st line setting should be explored. The use of the oral fluoropyrimidine, capecitabine, to replace infusional 5FU has been widely used for improved convenience and possible safety. We have chosen a modified biweekly CapeOx (capecitabine plus oxaliplatin) regimen due to its improved tolerance and response rate with a fixed dose of capecitabine given its widespread practice and ease of use.

Cetuximab Plus Biweekly Capecitabine and Oxaliplatin in KRAS Wild Type Metastatic Colorectal Cancer

A Phase II Study of Cetuximab Plus Biweekly Capecitabine and Oxaliplatin (C-CO2) in the Treatment of Patients With KRAS Wild Type Metastatic Colorectal Cancer

The tumor response rate (RR) will be defined as the total number of subjects whose best response is partial response (PR) or complete response (CR) during the first six months of treatment, divided by the number of subjects.

# of subjects who experienced \>= grade 1 adverse event that is positively related to treatment.

Time to Treatment Failure (progression or death) will be defined as the time from the first day of treatment until the date Progressive Disease (PD) or death is first reported. Subjects who die without a reported prior progression will be considered to have progressed on the day of their death. Subjects who did not progress will be censored at the day of their last tumor assessment.

Survival will be defined as the number of days from the first day of therapy to the date of death. If the subject is lost to follow-up, survival will be censored on the last date the subject was known to be alive.

Eli Lilly and Company

Bristol-Myers Squibb

NYU Langone Health

Cetuximab: 500 mg/m2, IV every two weeks

Oxaliplatin: 85 mg/m2, IV, q 2 weeks

Capecitabine: 2500 mg, po bid x 7 days every two weeks

Cetuximab, Capecitabine and Oxaliplatin

Age, Continuous

Sex: Female, Male

Asian

Black or African American

White

Unknown

Race/Ethnicity, Customized

United States

Region of Enrollment

Response Rate for the Combination Treatment

Toxicity Rates

Time to Progression

Survival

Overall Study

Heart and Blood Diseases

Carcinoma

Thrombosis

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Liver Diseases

Hematinics

Liver Extracts

Patients in the liver resection-based group received adjuvant PD-1 inhibitors plus targeted drugs following liver resection.

Patients in the locoregional treatment-based group received PD-1 inhibitors plus targeted drugs following locoregional therapy.

Patients in the intervention group received liver resection and postoperative adjuvant therapy

Liver resection

Patients in the control group received locoregional therapy and systemic therapy

Locoregional therapy

WanGuang Zhang

Hepatocellular carcinoma is prone to invade the portal vein and form portal vein thrombosis, and patients in this period are directly included in the advanced stages, i.e. Barcelona clinical liver cancer stage C. For the treatment of PVTT, there are differences between Eastern and Western guidelines, with systemic drugs being the standard of care in Western countries, while surgical treatment is often actively practiced in the Asia-Pacific region. More research is needed to explore the differences between these two approaches.

Hepatocellular carcinoma is prone to invade the portal vein and form portal vein thrombosis, and patients in this period are directly included in the advanced stages, i.e. Barcelona clinical liver cancer stage C. For the treatment of PVTT, there are differences between Eastern and Western guidelines, with systemic drugs being the standard of care in Western countries, while surgical treatment is often actively practiced in the Asia-Pacific region. In recent years, breakthroughs have been made in the treatment of advanced HCC, and systemic drug combinations such as PD-1 inhibitors combined with targeted therapies, and local area therapy combined with systemic therapy have shown excellent anti-tumor effects. Postoperative adjuvant therapy is also advancing, and the combination of adjuvant systemic medications for patients after PVTT has also been effective in reducing postoperative recurrence. Which approach is better for PVTT patients needs to be explored in depth.

Comparing the Prognosis of Patients With HCC and PVTT Treated With Surgery Versus Locoregional Therapy.

To Compare the Survival Differences in Patients With HCC and Portal Vein Tumor Thrombosis Treated With Liver Resection-based Therapy Versus Locoregional-based Therapy: a Prospective Cohort Study

Overall survival was defined as the period from study inclusion until death from any cause.

Adverse reactions are defined as any reaction during treatment that is inconsistent with the purpose of the treatment.

Chen Xiaoping

professor

Patients undergoing Transarterial chemoembolization

Combined therapy

Microwave ablation

Transarterial chemoembolization

Mohammad A Basha, Professor

The purpose of this study is to compare the safety and efficacy of combined therapy with conventional transarterial chemoembolization (cTACE) + microwave ablation (MWA) versus only TACE or MWA for treatment of hepatocellular carcinoma (HCC) \>3-\<5 cm.

This study aims to compare the safety and efficacy of combined therapy with conventional transarterial chemoembolization (cTACE)+microwave ablation (MWA) versus only TACE or MWA for treatment of hepatocellular carcinoma (HCC) \>3-\<5 cm.

This randomized controlled trial screened 278 patients with HCC \>3-\<5 cm. Patients were randomized into three groups: 90 underwent TACE (Group 1); 95 underwent MWA (Group 2); and 93 underwent combined therapy (Group 3). Patients were followed-up with contrast-enhanced CT or MRI. Images were evaluated and compared for treatment response and adverse events based on modified response evaluation criteria in solid tumor. Serum alpha-fetoprotein (AFP) concentration was measured at baseline and during every follow-up visit.

Patients were randomized into three groups: 90 underwent TACE (Group 1); 95 underwent MWA (Group 2); and 93 underwent combined therapy (Group 3).

Combined Therapy for Hepatocellular Carcinoma >3-<5 cm

Combined Therapy With Conventional Trans-arterial Chemoembolization (cTACE) and Microwave Ablation (MWA) for Hepatocellular Carcinoma >3-<5 cm

Images were evaluated and compared for adverse events. The adverse events were recorded and classiﬁed following the guidelines of the Society of Interventional Radiology

Tumor response was evaluated by CECT or dynamic MRI based on the modified response evaluation criteria in solid tumor (m-RECIST) established by the American Association for the Study of Liver Diseases.

The recurrence rate was measured in relation to management lines.

The mortality rate was measured in relation to management lines.

The progression-free survival was measured in relation to management lines.

The AFP variation rate (ΔAFP) was defined as the percentage of change between the AFP concentration at baseline and the postprocedure AFP concentration after 1-2 months as shown in the following equation:

ΔAFP (%) = \[(AFPbaseline-AFPpostprocedure) /AFPbaseline\] ×100%

Zagazig University

Assistant Professor

Micronutrients

Bone Density Conservation Agents

Vitamins

Amino Acids

Leucovorin

Fluorouracil

Lenvatinib

Immune Checkpoint Inhibitors

Levoleucovorin

Immunomodulating Agents

Calcium

Folic Acid

Calcium, Dietary

Tyrosine Kinase Inhibitors

Vitamin B Complex

Immunoglobulins, Intravenous

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

Tyrosine

Participants receive two cycles of HAIC (the drugs are oxaliplatin 135mg/m2 over 3hrs, calcium folinic acid 400mg/m2 or levofolinic acid 200mg/ m2 over 1.5hrs, 5-FU 400mg/m2 over 2hrs, 5-FU 2400mg/m2 over 46hrs,every 4 weeks) in combination with targeted drug (lenvatinib 8mg/day) and immunotherapy (PD-1 antibody, dosage and frequency according to instructions), then evaluate the response of tumor, those who achieve complete response (CR) will receive surgical resection or follow-up, those with partial response (PR) or stable disease (SD) continue two cycles of combined therapy, and those with progress disease (PD) will be withdrawn and receive other treatments. After four cycles of combined therapy, second evaluation of efficacy will be performed, those who achieve CR will receive surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.

Participants receive two cycles of HAIC (drugs of oxaliplatin 135 mg/m2 over 3 hours; calcium folinic acid 400 mg/m2 or levofolinic acid 200 mg/m2 over 1. 5 hours, 5-FU 400 mg/m2 over 2 hours, and 5-FU 2400 mg/m2 over 46 hours,every 4 weeks), then evaluate the response of tumor, and those who achieve complete response (CR ) will receive surgical resection or follow-up, while other patients continue to receive two cycles of combination therapy, i.e. HAIC combined with targeted drug (levatinib 8mg/day) and immunotherapy (PD-1 antibody, dose and frequency according to instructions). After four cycles, a second efficacy assessment will be performed, and patients who achieve CR will undergo surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.

Hepatic arterial infusion chemotherapy with (oxaliplatin 135mg/m2 over 3hrs, calcium folinic acid 400mg/m2 or levofolinic acid 200mg/ m2 over 1.5hrs, 5-FU 400mg/m2 over 2hrs, 5-FU 2400mg/m2 over 46hrs,every 4 weeks)

Oxaliplatin,calcium folinic acid, levofolinic acid, 5-FU

Lenvatinib 8mg/day combined with the HAIC from the first cycle

Concurrent Lenvatinib

PD-1 antibody which is approved by authorities for HCC treatment combined with the HAIC from the first cycle (dosage and frequency according to instructions)

Concurrent PD-1 antibody

Lenvatinib 8mg/day combined with the HAIC from the third cycle for those patients who do not achieve complete response (CR)

Sequential Lenvatinib

PD-1 antibody which is approved by authorities for HCC treatment combined with the HAIC from the third cycle for those patients who do not achieve complete response (CR) (dosage and frequency according to instructions)

Sequential PD-1 antibody

Shao Hua Li, Ph.D, M,D

Rong Ping Guo, M,D

Shao Hua Li, Ph.D, M.D

Wei Wei, Ph.D, M.D

Wei Wei, Ph.D, M,D

The goal of this clinical trial is to compare HAIC concurrently with sequentially combined with targeted and immunotherapies in terms of efficacy and safety in patients with potentially resectable intermediate and advanced HCC (CNLC stage IIa\~IIIa). The main questions it aims to answer are:

* Does a "strong combination" regimen of three simultaneous treatments (HAIC, targeted agents and immunotherapy) definitely result in a higher surgical conversion rate and better survival benefit?
* Can the combination of targeted and immunotherapies based on patients' response to HAIC therapy avoid over-treatment of some patients without affecting the surgical conversion rate and overall survival? Participants will be randomly assigned to receive either HAIC concurrently or sequentially combined with targeted and immunotherapies.

Researchers will compare concurrent treatment group with sequential treatment group to see if there are different in terms of the conversion resection rate, long-term survival, and safety.

Participants in the concurrent treatment group will receive two cycles of HAIC (the drugs are oxaliplatin 135mg/m2 over 3hrs, calcium folinic acid 400mg/m2 or levofolinic acid 200mg/ m2 over 1.5hrs, 5-FU 400mg/m2 over 2hrs, 5-FU 2400mg/m2 over 46hrs,every 4 weeks) in combination with targeted drug (lenvatinib 8mg/day) and immunotherapy (PD-1 antibody, dosage and frequency according to instructions), then evaluate the response of tumor, those who achieve complete response (CR) will receive surgical resection or follow-up, those with partial response (PR) or stable disease (SD) continue two cycles of combined therapy, and those with progress disease (PD) will be withdrawn and receive other treatments. After four cycles of combined therapy, second evaluation of efficacy will be performed, those who achieve CR will receive surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.

Participants in the sequential treatment group will receive two cycles of HAIC (drugs of oxaliplatin 135 mg/m2 over 3 hours; calcium folinic acid 400 mg/m2 or levofolinic acid 200 mg/m2 over 1. 5 hours, 5-FU 400 mg/m2 over 2 hours, and 5-FU 2400 mg/m2 over 46 hours,every 4 weeks), then evaluate the response of tumor, and those who achieve complete response (CR ) will receive surgical resection or follow-up, while other patients continue to receive two cycles of combination therapy, i.e. HAIC combined with targeted drug (levatinib 8mg/day) and immunotherapy (PD-1 antibody, dose and frequency according to instructions). After four cycles, a second efficacy assessment will be performed, and patients who achieve CR will undergo surgical resection or follow-up observation, and the other patients will be evaluated for the possibility of surgical resection or the subsequent treatment.

Concurrently vs Sequentially Combined HAIC With Targeted and Immunotherapy in Potentially Resectable HCC

A Randomized Controlled Study of the Efficacy of Hepatic Arterial Perfusion Chemotherapy Concurrently Compared to Sequentially Combined With Targeted and Immunotherapy in Potentially Resectable Intermediate and Advanced HCC

From the perspective of protecting the privacy of participants, there was no participant data (IPD) plan in this study.

Progression-free survival of the participants

Objective response rates, which means the proportion of patients with efficacy assessment of complete response and partial response for the size of intrahepatic target lesions according to mRECIST criteria and RECIST v1.1 criteria respectively.

Disease control rates, which means the proportion of patients with efficacy assessment of complete response, partial response and stable disease for the size of intrahepatic target lesions according to mRECIST criteria and RECIST v1.1 criteria respectively.

Conversion resection rate refer to the proportion of patients in both groups who actually underwent subsequent surgical resection.

Adverse Events and Severe Adverse Events evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cetuximab Plus Biweekly Capecitabine and Oxaliplatin in KRAS Wild Type Metastatic Colorectal Cancer	NCT00444678	Colorectal Canc... Neoplasm Metast...	Cetuximab Oxaliplatin Capecitabine	18 Years -	NYU Langone Health
Comparing the Prognosis of Patients With HCC and PVTT Treated With Surgery Versus Locoregional Therapy.	NCT06248528	Hepatocellular ...	Liver resection Locoregional th...	18 Years - 75 Years	Tongji Hospital
Combined Therapy for Hepatocellular Carcinoma >3-<5 cm	NCT04721470	Hepatocellular ...	Combined therap... Microwave ablat... Transarterial c...	18 Years - 80 Years	Zagazig University
Concurrently vs Sequentially Combined HAIC With Targeted and Immunotherapy in Potentially Resectable HCC	NCT06041477	Hepatocellular ... Chemotherapy Ef... Chemotherapeuti...	Oxaliplatin,cal... Concurrent Lenv... Concurrent PD-1... Sequential Lenv... Sequential PD-1...	18 Years - 75 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for combined therapy