Aflibercept 4 mg/kg administered over 1 hour on Day 1, followed by FOLFIRI regimen. Treatment will be repeated every 2 weeks. FOLFIRI regimen: Irinotecan 180 mg/m² intravenous (IV) infusion and folinic acid 400 mg/m² IV infusion followed by: 5-fluorouracil (5-FU) 400 mg/m² IV bolus followed by: 5-FU 2400 mg/m² continuous IV infusion over 46 hours. FOLFIRI administration will immediately follow the aflibercept one. In the absence of PD after 6 months of the combination of chemotherapy and aflibercept, the patient will be treated with a maintenance therapy with aflibercept alone until PD or unacceptable toxicities, investigator's decision or patient's refusal of further treatment or death, whichever comes first.

Metastatic Colorectal Cancer

AFLIBERCEPT

Irinotecan

5-Fluorouracil

Folinic Acid

Agios Georgios Chania General Hospital

2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital

251 Airforce Hospital

2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio"

Oncology Unit, 3rd Dept of Internal Medicine, Athens School of Medicine, Sotiria General Hospital

Oncology Section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra"

Division of Oncology, 2nd Dept of Internal Medicine, University Hospital "Attiko"

2nd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

3rd Dept of Medical Oncology, Hygeia Hospital

1st Dept of Medical Oncology, Metropolitan Hospital

2nd Dept of Medical Oncology, Metropolitan Hospital

Dept of Medical Oncology, University Hospital of Heraklion

Dept of Medical Oncology, Ioannina University Hospital

Oncology Dept, University Hospital of Larissa

Division of Oncology, Dept of Internal Medicine, University Hospital of Patras

Thermi Clinic S.A.

Dept of Medical Oncology, Papageorgiou General Hospital

﻿Clinical Trial of Combination Chemotherapy With Aflibercept in Patients With Advanced Colorectal Cancer

﻿Single-arm Phase II Study of Maintenance Therapy With Aflibercept After First-line Treatment With FOLFIRI Plus Aflibercept in Metastatic Colorectal Cancer Patients

Response to treatment will be described in a frequency table along with the corresponding percentages and 95% exact confidence intervals.

Adverse Events of the safety population for the FOLFIRI-aflibercept treatment part and the maintenance therapy will be presented in frequency tables according to grade, along with the corresponding percentages (N,%)

Hellenic Cooperative Oncology Group

Sanofi

Methotrexate (12 g/m2 x 1, intravenously) with standard folinic acid rescue
In arm A patients will receive cycle M first followed by cycle GluM. Cycle M starts with course M1 on day 1 followed by course M2 planned for day 8. Cycle GluM starts with course GluM1 on day 1 followed by GluM2 planned for day 8. Cycle GluM will not start for a minimum of 14 days from the beginning of course M2, or until bone marrow, renal and hepatic functions have completely recovered and the patient is clinically ready to receive further chemotherapy .

Methotrexate (12 g/m2 x 1, intravenously) with folinic acid and glucarpidase rescue (50 units/kg x 1, intravenously).
In arm B, patients will receive cycle GluM first followed by cycle M. Cycle GluM starts with course GluM1 on day 1 followed by GluM2 planned for day 8.Cycle M starts with course M1 on day 1 followed by course M2 planned for day 8. Cycle M will not start for a minimum of 14 days from the beginning of course GluM2, or until bone marrow, renal and hepatic function have completely recovered and the patient is clinically ready to receive further chemotherapy

Osteosarcoma

Spindle Cell Sarcoma of Bone

Glucarpidase rescue (50 units/kg x 1, intravenously)

Glucarpidase

Methotrexate (12 g/m2 x 1, intravenously)

Methotrexate

Folinic acid rescue 15mg/m2 four times daily adjusted according to methotrexate levels

University College Hospital

Will Glucarpidase After Methotrexate Treatment for Bone Sarcoma Lead to Fewer Side Effects and Reduce Chemotherapy Delays?

A Randomised, Cross-over Phase II Study to Investigate the Efficacy and Safety of Glucarpidase for Routine Use After High Dose Methotrexate in Patients With Bone Sarcoma

The first day of each cycle is denoted Day 1. Therefore, the primary outcome will be the proportion of patients who are clinically fit to start cycle 2 of chemotherapy 14 days later.

Incidence and grading of mucositis, renal toxicity, liver toxicity, neutropaenia, thrombocytopaenia and infections

Each cycle lasts 3 weeks and patients receive two treatment cycles. The time frame will therefore be 6 weeks

Completion of quality of life questionnaires at Day 1, 8, 15 each cycle

Day 1, 8, 15 each cycle. Day 30 cycle 2, 3 and 6 months from entry

Grading of mucositis, renal toxicity, liver toxicity, neutropaenia, thrombocytopaenia and infections

Duration in days of mucositis, renal toxicity, liver toxicity, neutropaenia, thrombocytopaenia and infections

University College, London

Richard Scowcroft Foundation

Colorectal Cancer

Standard 5-fluorouracil (5-FU) chemotherapy (400 milligram per square meter [mg/m^2] administered as intravenous bolus and then 5-FU 2400 mg/m^2 administered as continuous intravenous infusion over 46 +/- 2 hours) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.

5-fluorouracil

Cetuximab 400 mg/m^2 intravenous infusion as a loading dose on Day 1 Cycle 1, followed by 250 mg/m^2 intravenous infusion weekly until documented disease progression or unacceptable toxicity.

Cetuximab

Standard Irinotecan chemotherapy (180 milligram per square meter [mg/m^2] administered as intravenous infusion over 60 +/- 30 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.

Standard Leucovorin chemotherapy (400 mg/m^2 [racemic form] or 200 mg/m^2 [L-isomer form] administered by intravenous infusion over 120 +/- 10 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.

Leucovorin

MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.

MEHD7945A

Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)

A Phase II, Multicenter, Open-Label, Randomized Study Evaluating the Efficacy and Safety of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI in Second Line in Patients With KRAS Wildtype Metastatic Colorectal Cancer

Genentech, Inc.

Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-fluorouracil (5-FU)/folinic acid (FA). Cetuximab was always administered every 7 days with an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Subjects received FOLFOX-4 chemotherapy regimen that consists of a combination of oxaliplatin with 5-FU/FA. Oxaliplatin 85 mg/m^2 infused over 120 minutes was administered first or simultaneously with FA at a dose of 200 mg/m^2 infused over 120 minutes on Day 1, Day 2, and every 2 weeks and then 5-FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Subjects received cetuximab in combination with FOLFOX-4 chemotherapy regimen. FOLFOX-4 chemotherapy regimen consists of a combination of oxaliplatin with 5-FU/FA. Cetuximab was always administered every 7 days with an initial dose of 400 mg/m^2 at 5 mg/min and 250 mg/m^2 at 10 mg/min for subsequent infusions, followed by oxaliplatin 85 mg/m^2 infused over 120 minutes at least 1 hour later. Following completion of the oxaliplatin infusion or simultaneously with oxaliplatin, FA was administered at a dose of 200 mg/m^2 infused over 120 minutes, on Day 1, Day 2, and every 2 weeks and then 5- FU was administered as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infused over 22 hours, on Day 1, Day 2, and every 2 weeks. All subjects received treatment until progression of disease, withdrawal of consent, or unacceptable toxicity.

Cetuximab + FOLFOX-4

FOLFOX-4

Total

Sex: Female, Male

PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the Independent Review Committee (IRC) according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.

Progression Free Survival (PFS) Time

OS was defined as the time (in months) from randomization to death. For subjects who were still alive at the analysis data cut-off date or who lost to follow-up, survival was censored at the last recorded date that the subject was known to be alive.

Overall Survival (OS) Time

The Best ORR was defined as the percentage of subjects having achieved complete response (CR) or partial response (PR) according to RECIST version 1.0 as determined by the IRC. CR: defined as disappearance of all target and all non-target lesions and no new lesions. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions and no new lesions.

Best Overall Response Rate (ORR)

TTF was defined as time from randomization to date of the first occurrence of radiologically confirmed PD as determined by IRC, Clinical PD according to the Investigator's assessment (if radiological confirmation of PD by IRC was unavailable), discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death within 90 days of last tumor assessment or randomization. Subjects without event were censored on the date of last tumor assessment.

Time to Treatment Failure (TTF)

The number of subjects who underwent liver metastatic surgery after start of treatment and the outcome of surgery with respect to residual tumor after surgery (R0, R1, R2, not evaluable) were summarized. In case of resection of more than one metastasis, the worst outcome of surgery defined the overall status of a subject. R0 = No residual tumor after resection (all lesions resected completely); R1 = Metastases not resected completely with microscopic residual lesions; and R2 = Metastases not resected completely with macroscopic residual lesions.

Number of Subjects With Curative Surgery of Liver Metastases

Cetuximab + FOLFOX4

FOLFOX4

Overall Study

Communication Center

Cetuximab was administered every 7 days at an initial dose of 400 milligram per square meter (mg/m^2) at 5 milligram per minute (mg/min) and 250 mg/m^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity to cetuximab.

Oxaliplatin 85 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Oxaliplatin

FA 200 mg/m^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

5-FU as a bolus of 400 mg/m^2/day intravenously over 2-4 minutes followed by 600 mg/m^2/day infusion over 22 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

5Fluorouracil

Fujian Province Cancer Hospital

Fuzhou General Hospital

First Hospital Affiliated to Guangzhou University of Chinese Medicine

Nanfang Hospital

The Tumor Hospital of Harbin Medical University

Union Hospital of Tongji Medical College of Huazhong University of Science and Technology

Jilin Cancer Hospital

First Affiliated Hospital of Jilin University

The Affiliated Hospital of Medical College Qingdao University

The First Affiliated Hospital of College of Medicine, Zhejiang University

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

307 Hospital of PLA

The General Hospital of the People's Liberation Army

Affiliated Hospital of Bengbu Medical College

The Xiangya 2nd Hospital of Central South University

Southwest Hospital

Yunnan Provincial Tumor Hospital

The First Affiliated Hospital of Nanchang University

Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine

Fudan University Shanghai Cancer Center

Shanghai First People's Hospital

Fudan University Zhongshan Hospital

The First Affiliated Hospital of Soochow University

Tianjin People's Hospital

Xijing Hospital the 4th Military Medical University of PLA

A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-Fluorouracil (5FU) Combination Chemotherapy (FOLFOX-4) With or Without Cetuximab in the 1st Line Treatment of Metastatic Colorectal Cancer (mCRC) in Chinese Rat Sarcoma Viral Oncogene Homolog (RAS) Wild-type Patients

An Open-label, Randomized, Controlled, Multicenter Phase III Trial to Compare Cetuximab in Combination With FOLFOX-4 Versus FOLFOX-4 Alone in the First Line Treatment of Metastatic Colorectal Cancer in Chinese Subjects With RAS Wild-type Status

folinic acid/sarkoma

Clinical Trial of Combination Chemotherapy With Aflibercept in Patients With Advanced Colorectal Cancer

Will Glucarpidase After Methotrexate Treatment for Bone Sarcoma Lead to Fewer Side Effects and Reduce Chemotherapy Delays?

Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)

A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-Fluorouracil (5FU) Combination Chemotherapy (FOLFOX-4) With or Without Cetuximab in the 1st Line Treatment of Metastatic Colorectal Cancer (mCRC) in Chinese Rat Sarcoma Viral Oncogene Homolog (RAS) Wild-type Patients

Išsamiausia vaistinių žolelių duomenų bazė, paremta mokslu

folinic acid/sarkoma

﻿Clinical Trial of Combination Chemotherapy With Aflibercept in Patients With Advanced Colorectal Cancer

Will Glucarpidase After Methotrexate Treatment for Bone Sarcoma Lead to Fewer Side Effects and Reduce Chemotherapy Delays?

Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)

A Trial to Compare Oxaliplatin, Folinic Acid (FA) and 5-Fluorouracil (5FU) Combination Chemotherapy (FOLFOX-4) With or Without Cetuximab in the 1st Line Treatment of Metastatic Colorectal Cancer (mCRC) in Chinese Rat Sarcoma Viral Oncogene Homolog (RAS) Wild-type Patients

Išsamiausia vaistinių žolelių duomenų bazė, paremta mokslu

Clinical Trial of Combination Chemotherapy With Aflibercept in Patients With Advanced Colorectal Cancer