Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Bevacizumab

Nintedanib

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Bevacizumab 5mg/kg once daily every other week

BIBF 1120

mFolfox

mFolfox 6

bevacizumab

Boehringer Ingelheim

The primary objective of this study is to evaluate PFS rate at 9 months of BIBF 1120 in combination with mFolfox6 compared with mFolfox6 combined to bevacizumab in first line patients with metastatic colorectal cancer.

BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer

A Phase I-II Study of BIBF 1120 and FOLFOX Compared to Bevacizumab and FOLFOX in First Line Metastatic Colorectal Cancer Patients

PFS-9 is defined as the time from first treatment with the trial drug until either the onset of progressive disease or death. A patient is defined as progression-free for 9 months if their PFS was at least 270 days. Progression is assessed according to following mentioned RECIST criteria (version 1.0).

1. 20% increase in the sum of the longest diameter of target lesions.
2. The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Overall survival is defined as the time from first treatment until death. Greenwood variance was used for the calculation of 95% confidence interval.

PFS is defined as the time from first treatment with the trial drug until either the onset of progressive disease or death throughout the whole study. Progression is assessed according to RECIST criteria (version 1.0). In this endpoint, the Greenwood's variance estimate was used to calculate the Kaplan-Meier progression free survival median and its corresponding 95% confidence interval

Objective response rate is defined as a best response of either complete (CR) or partial response (PR) according to RECIST version 1.0. To be assigned a status of PR or CR, changes in tumour measurements had to be confirmed by repetition of the CT or MRI scan no less than 4 weeks after the criteria for response were first met. This confirmation was necessary to avoid overestimating the response rate observed. The 95% confidence interval represent the Clopper-Pearson exact confidence interval

Objective response is defined as a best response of either complete (CR) or partial response (PR) according to RECIST version 1.0. To be assigned a status of PR or CR, changes in tumour measurements had to be confirmed by repetition of the CT or MRI scan no less than 4 weeks after the criteria for response were first met. This confirmation was necessary to avoid overestimating the response rate observed. The 95% Confidence interval represent the Clopper- Pearson exact confidence interval.

Surgical excision of the lesions is allowed if the previous assessment of tumoral response occurred after at least 6 cycles of treatment. Resection Rate includes resection rates R0, R1 and R2 before progressive disease.

Peto's variance estimate was used.

For each patient, the minimum percentage increase from baseline measurement (≤ 28 days before the beginning of the treatment) of the sum Longest diameter (LD) of target lesions was calculated based on the measurements of tumor size. The minimum percentage increase has been divided to four groups:

1. \<= - 30%
2. \> - 30% and \< 0%
3. \>= 0% and \< 20%
4. \>=20%

Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).

Percentage of patients with DLTs,AE were observed in Gastrointestinal,Hepatobiliary \& skin and subcutaneous tissue disorder.Drug related DLT was defined:1)Gastrointestinal toxicity(vomiting, nausea and diarrhoea)or hypertension of CTCAEgrade(G)3 despite optimal supportive care/intervention.2)Non-haematological toxicity of G≥3 except AE:alopecia,nail modifications,\& isolated elevation of gamma glutamyl transpeptidase.3)G4 neutropenia for\>7days(not associated with fever≥38.5°C).4)Neutropenia of G≥3 of any duration associated with fever≥38.5ºC.5)Platelets \<25,000/μLorG3 thrombocytopenia associated with bleeding requiring transfusion.6)Inability to resume nintedanib dosing within14days of stopping due to treatment related toxicity.7)ALT and/or AST elevation of G≥3orG≥2 in conjunction with bilirubin G\>1. 8)Inability to recover from increase ALT/AST in conjunction with increase of bilirubin toALT/AST toG≤1 \&bilirubin to normal or baseline within14days after nintedanib treatment interruption

Determination of Maximum Tolerable Dose based on DLT incidence.

Area under the plasma concentration time-curve over 12 hours for Nintedanib in the dosing interval at steady state and normalized by the dosing unit administered (AUCtau,ss,norm) (Phase I)

Maximum plasma concentration for Nintedanib at steady state and normalized by the dosing unit administered (Cmax,ss,norm) (Phase I)

Quality of life evaluation by a standardised questionnaires of European Organisation for Research and Treatment of Cancer (EORTC): EORTC-QLQ-C30 for the change from baseline at 9 months for Global health status scores.

Raw scores are transformed to scales of 0-100. A higher score is associated with a better quality of life for Global health status scores

Quality of life evaluation by a standardised questionnaires of European Organisation for Research and Treatment of Cancer (EORTC): EORTC-QLQ-CR38 for the change from baseline at 9 months for functional scales, Symptom scales Chemotherapy side effects .

The EORTC-QLQ-CR38 was composed of functioning scales (body image, future perspective, sexual enjoyment, sexual functioning) and symptom scales (chemotherapy side effects, defecation problems, symptoms of the gastrointestinal tract, micturition problems,female sexual problems, male sexual problems, stoma related problems, and weight loss).

Raw scores are transformed to scales of 0-100. A higher score is associated with a better quality of life for functional scales and a worse quality of life for symptom scales.

Number of participants for Quality of life evaluation by a standardised questionnaires of European Organisation for Research and Treatment of Cancer (EORTC): EORTC-QLQ-CR38 for the first use of stoma bag.

Exploratory biomarker and pharmacogenetic analysis for Vascular endothelial growth factor (VEGF).

Note: This endpoint was not statistically analysed in this study.

Patients receiving nintedanib 150 mg or 200 mg twice daily plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).

Nintedanib + mFolfox6

Patients receiving bevacizumab 5 mg/kg every other week plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)

Bevacizumab + mFolfox6

Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).

Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).

Total

Age, Continuous

Sex: Female, Male

Treated Set (TS) - The treated set includes all patients who were dispensed and were documented to have taken at least one dose of the trial drug.

Boehringer Ingelheim Call Center

Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)

Progression-free Survival Rate at 9 Months (PFS-9)

Overall Survival

Progression-free Survival (PFS)

Confirmed Objective Response Rate

Unconfirmed Objective Response Rate

Resection Rate

<=-30%

> - 30% and < 0%

>= 0% and < 20%

>=20%

Non-evaluable

Tumor Shrinkage

CTCAE Grade 1

CTCAE Grade 2

CTCAE Grade 3

CTCAE Grade 4

CTCAE Grade 5

Incidence and Intensity of Adverse Events With Grading According CTCAE

Diarrhoea

Hepatotoxicity

Rash maculo-papular

Patients receiving nintedanib 150 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)

Nintedanib 150 mg + mFolfox6 (Phase I)

Patients receiving nintedanib 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).

Nintedanib 200 mg + mFolfox6 (Phase I)

MTD set: The first 12-18 patients randomised to the nintedanib treatment group, treated with nintedanib according to the dose escalation part of the study. The outputs (updated with cleaned and more complete data) that were used to decide on the MTD of nintedanib while the study was ongoing.

Percentage of Patients With Dose Limit Toxicity (DLTs) Incidence During the First Two Treatment Cycles (Phase I).

Maximum Tolerable Dose (MTD)

Patients receiving nintedanib 150 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).

Patients receiving nintedanib 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)

Area Under the Plasma Concentration Time-curve Over 12 Hours for Nintedanib in the Dosing Interval at Steady State and Normalized by the Dosing Unit Administered (AUCtau,ss,Norm) (Phase I)

Maximum Plasma Concentration for Nintedanib at Steady State and Normalized by the Dosing Unit Administered (Cmax,ss,Norm) (Phase I)

Treated Set (TS). Number of analysed patients are the total number of patients who were analysed for the change from baseline at 9 months for Global health status scores

Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-C30 for the Change From Baseline at 9 Months of Global Health Status Scores.

Body image (N=24, 11)

Future perspective (N=25, 11)

Sexual enjoyment (N=2, 3)

Sexual functioning (N=15, 7)

Chemotherapy side effects (N=25, 11)

Defaecation problems (N=17, 8)

Female sexual problems (N=0, 0)

Male sexual problems (N=5, 4)

Micturition problems (N=25,11)

Stoma-related problems (N=4, 2)

Symptoms area of gastro-intestinal tract (N=25,11)

Weight loss (N=25,11)

Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.

Baseline

Week 6

Week 12

Week 24

Week 30

Week 54

No use of stoma bag

Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.

Exploratory Biomarker and Pharmacogenetic Analysis for VEGF

Nintedanib 150 mg + mFolfox6

Nintedanib 200 mg + mFolfox6

Bevacizumab 5 mg + mFolfox6 (Phase II)

Overall Study

Infections

Rare Diseases

Sarcoma

Virus Diseases

Rectal Neoplasms

Colonic Neoplasms

Soft Tissue Sarcoma

Micronutrients

Herbal and Botanical

Antibodies

Antibodies, Monoclonal

Leucovorin

Fluorouracil

Oxaliplatin

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Panitumumab

Cola

Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and modified FOLFOX6 (mFOLFOX6) chemotherapy regimen consisting of oxaliplatin (85 mg/m\^2), leucovorin (400 mg/m\^2) and 5-fluorouracil (5-FU) (2400 mg/m\^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 regimen consisting of oxaliplatin (85 mg/m\^2), leucovorin (400 mg/m\^2), followed by 5-FU (2400 mg/m\^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).

Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).

mFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m\^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m\^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m\^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m\^2) via ambulatory pump administered for a period of 46 to 48 hours.

mFOLFOX6

The primary objective of this study is to estimate the treatment effect on progression-free survival (PFS) of panitumumab relative to bevacizumab in combination with mFOLFOX6 chemotherapy as first-line therapy in patients with tumors expressing wild-type KRAS, unresectable mCRC.

PEAK: Panitumumab Plus mFOLFOX6 vs. Bevacizumab Plus mFOLFOX6 for First Line Treatment of Metastatic Colorectal Cancer (mCRC) Patients With Wild-Type Kirsten Rat Sarcoma-2 Virus (KRAS) Tumors

A Randomized, Multicenter, Phase 2 Study to Compare the Efficacy of Panitumumab in Combination With mFOLFOX6 to the Efficacy of Bevacizumab in Combination With mFOLFOX6 in Patients With Previously Untreated, KRAS Wild-Type, Unresectable, Metastatic Colorectal Cancer

PFS was defined as the time from the date of randomization to the date of first disease progression, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever was later). Participants not meeting the criteria by the cutoff date were censored at the last evaluable tumor assessment date. Tumor response was evaluated by the investigator per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 every 8 weeks until radiographic disease progression. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.

Overall survival was defined as the time from randomization to the date of death, with participants alive or lost to follow-up at the analysis data cutoff date censored at their last contact date.

Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met. Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.

For participants with a confirmed objective response, the time from first confirmed objective response to radiologic disease progression per modified RECIST 1.0 criteria or death. For participants who responded and have not progressed or died, duration of response was censored at their last evaluable disease assessment date.

Time to progression (TTP) is defined as the time from randomization to the date of radiologic disease progression per modified RECIST 1.0 criteria. Participants not meeting criteria for disease progression by the analysis data cutoff date were censored at their last evaluable disease assessment date. Progression is defined as at least a 20% increase in the size of target lesions, unequivocal progression of existing non-target lesions, or any new lesions.

For participants with a confirmed objective response, the time from randomization to the date of first confirmed objective response. Assessments are based on the investigator's review of scans using a modified-RECIST v1.0. An objective response is defined as a best tumor response of complete or partial response. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met.

The resection rate was defined as the percentage of participants with a surgical procedure that resulted in partial reduction or complete eradication of all metastatic disease.

Objective response was defined as having a confirmed complete response (CR) or partial response (PR) during first-line treatment, based on the investigator's review of scans using a modified-RECIST v1.0. A complete or partial response was confirmed no less than 4-weeks after the criteria for response were first met.

Complete Response: Disappearance of all target and non-target lesions and no new lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions and no progression of non-target lesions and no new lesions, or the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease and no new lesions.

Severity was graded using Common Terminology Criteria for Adverse Events (CTCAE) v3.0, with the exception of some dermatology/skin adverse events that were graded using CTCAE v3.0 with modifications. Fatal adverse events are classified as grade 5. Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related AEs were those that the investigator considered a reasonable possibility that might have been caused by study drug.

Amgen

The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.

Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.

Panitumumab Plus mFOLFOX6

Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 chemotherapy regimen on Day 1 of every 14-day cycle.

Bevacizumab Plus mFOLFOX6

White or Caucasian

Black or African American

Hispanic or Latino

Asian

Japanese

Race/Ethnicity, Customized

Prior Adjuvant Oxaliplatin Therapy

BRAF wild-type

RAS Wild-type

RAS/BRAF wild-type

Testing not performed

Sample acceptance failure

This analysis was performed on tumors from 136 and 137 participants in each treatment group respectively. BRAF = v-raf murine sarcoma viral oncogene homolog B1; RAS = rat sarcoma viral oncogene homolog, and includes Kirsten rat sarcoma-2 viral oncogene (KRAS) exons 2, 3 \& 4 and neuroblastoma RAS viral (v-ras) oncogene (NRAS) exons 2, 3, and 4. Participants may appear in more than one category.

RAS and BRAF Mutation Status

Study Director

Intent-to-treat (ITT) analysis set (all randomized participants)

Evaluable for Local Tumor Response Analysis Set, defined as the subset of participants in the ITT Analysis Set who had at least 1 unidimensionally measurable lesion per modified RECIST 1.0 per the local investigator.

Percentage of Participants With an Objective Response

Evaluable for Local Tumor Response Analysis Set: Responders

Duration of Response

Time to Disease Progression

Time to Initial Objective Response

Wild-type RAS Efficacy Analysis Set, defined as a subset of Wild-type KRAS Exon 2 Efficacy Analysis Set including all randomized participants with wild-type KRAS exon 2, 3, 4, NRAS exon 2, 3, and 4.

Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS)

Wild-type RAS/BRAF Efficacy Analysis Set was defined as a subset of Wild-type KRAS Exon 2 Efficacy Analysis Set with wild-type KRAS exon 2, 3, and 4, NRAS exon 2, 3, 4, and BRAF exon 15.

Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)

Overall Survival in Participants With Wild-type RAS

Overall Survival in Participants With Wild-type RAS / BRAF

Wild-type RAS Investigator Tumor Response Analysis Set, defined as the subset of participants in the Wild-type RAS Efficacy Analysis Set who had at least 1 unidimensionally measurable lesion per modified RECIST 1.0 per the local investigator.

Percentage of Participants With an Objective Response for Participants With Wild-type RAS

Wild-type RAS/BRAF Investigator Tumor Response Analysis Set, defined as the subset of participants in the Wild-type RAS/BRAF Efficacy Analysis Set who had at least 1 unidimensionally measurable lesion per modified RECIST 1.0 per the local investigator.

Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF

Any adverse event (AE)

AE with worst grade of 3

AE with worst grade of 4

AE with worst grade of 5

Serious adverse event (SAE)

AE leading to discontinuation of study drug

Safety analysis set, which included all randomized participants who received at least 1 dose of protocol treatment (ie, panitumumab, bevacizumab, or any component of mFOLFOX6).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer	NCT00904839	Colorectal Neop...	BIBF 1120 BIBF 1120 mFolfox Bevacizumab mFolfox 6 bevacizumab	18 Years -	Boehringer Ingelheim
PEAK: Panitumumab Plus mFOLFOX6 vs. Bevacizumab Plus mFOLFOX6 for First Line Treatment of Metastatic Colorectal Cancer (mCRC) Patients With Wild-Type Kirsten Rat Sarcoma-2 Virus (KRAS) Tumors	NCT00819780	Colon Cancer Colorectal Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab mFOLFOX6	18 Years -	Amgen
Assessment of Ramucirumab Plus Paclitaxel as Switch MANteInance Versus Continuation of First-line Chemotherapy in Patients With Advanced HER-2 Negative Gastric or Gastroesophageal Junction Cancers	NCT02934464	Stomach Neoplas...	RAMUCIRUMAB Paclitaxel FOLFOX 4 mFOLFOX 6 XELOX	18 Years -	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer	NCT00904839	Colorectal Neop...	BIBF 1120 BIBF 1120 mFolfox Bevacizumab mFolfox 6 bevacizumab	18 Years -	Boehringer Ingelheim
PEAK: Panitumumab Plus mFOLFOX6 vs. Bevacizumab Plus mFOLFOX6 for First Line Treatment of Metastatic Colorectal Cancer (mCRC) Patients With Wild-Type Kirsten Rat Sarcoma-2 Virus (KRAS) Tumors	NCT00819780	Colon Cancer Colorectal Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab mFOLFOX6	18 Years -	Amgen

Spots Global Cancer Trial Database for mfolfox 6

Every month we try and update this database with for mfolfox 6 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 mfolfox 6

Every month we try and update this database with for mfolfox 6 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 mfolfox 6 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.