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

Micronutrients

Hematinics

Vitamins

Irinotecan

Cetuximab

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Folic Acid

Antineoplastic Agents, Immunological

Folinic Acid

Folate

Vitamin B9

modifiedFOLFOX6 + Cetuximab oxaliplatin 85 mg/m2 on day 1, 15 q d29 for 6 cycles folinic acid (FA) 400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus day 1 + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly

FOLFIRI + Cetuximab irinotecan 180 mg/m² on day 1, 15 q d29 for 6 cycles folinic acid (FA)400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly

FOLFIRI + Cetuximab

modifiedFOLFOX6 + Cetuximab

Thomas Winder, MD

This pilot study is being mounted to assess whether treatment assignment by ERCC-1 gene expression status suggests better clinical results from historical experience in metastatic colorectal cancer (mCRC). In wild type KRAS mCRC patients treated with either FOLFOX or FOLFIRI in combination with cetuximab the median response rate is approximately 60-65%. Biomarker directed treatment in this study may demonstrate that patients with low ERCC-1 treated with FOLFOX and cetuximab, and those with high ERCC-1 treated with FOLFIRI and cetuximab, will improve response rate to 70-75%. KRAS wild type patients will be treated with 6 cycles of one of the following regimens chosen for optimization based on patient characteristics (primary treatment phase). Patients with ERCC-1 \< 1.7 relative gene expression of ERCC-1 over ß-actin (ERCC-1 low) will be assigned to treatment with mFOLFOX6 in combination with Cetuximab. Patients with ERCC-1 gene expression \> 1.7 relative gene expression of ERCC-1 over over ß-actin (ERCC-1 high) will be assigned to treatment with FOLFIRI in combination with Cetuximab.

Biomarker Directed Treatment in Metastatic Colorectal Cancer

Pilot Study: Biomarker Directed Treatment in Metastatic Colorectal Cancer

Treatment response according to Response Evaluation Criteria In Solid Tumors \[RECIST\]

Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to response rate, PFS and OS

Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to KRAS status

Merck Sharp & Dohme LLC

Arbeitsgemeinschaft medikamentoese Tumortherapie

Skin and Connective Tissue Diseases

Exanthema

Skin Diseases

Coagulants

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Mitogens

Vitamin B Complex

Vitamin K

Vitamin K 1

Menadione

Menaquinone

Naphthoquinone

Phylloquinone

1. Cetuximab (Erbitux® )- Cetuximab is a recombinant IgG1 chimeric monoclonal antibody directed against human epidermal growth factor receptor (EGFR).
2. FOLFIRI regimen

Administration Schedule:

Cetuximab at a initial dose 400 mg/sqm (first week), then 250 mg/sqm on day 1 and 8 Background Chemotherapy (every two weeks)

* Irinotecan 180 mg/m² iv , 90 min on day 1
* Folic acid (racemic) 400 mg/m², 120 min on day 1
* 5-FU 400 mg/m² bolus on day 1
* 5-FU 2400 mg/m² iv over 46 h on day 1 to 2

Carl Christoph Schimanski, PD Dr. med.

The purpose of this interventional study is to assess the progression free survival (one year) of patients with treatment of FOLFIRI and cetuximab, combined with an optional dermal prophylaxis.

Further Objectives:

1. Development of acneiforme follicular exanthema \>= grade 2
2. Duration until development of acneiforme follicular exanthema \>= grade 2
3. Development of paronychia
4. Development skin fissure (hand and foot)
5. Objective remission according RECIST 1.1
6. Rate of secondary resections of liver metastasis with a curative approach
7. Assessment of safety and tolerability
8. Overall survival
9. Progression free survival

Subjects with metastatic colorectal cancer and confirmed KRAS-wildtype status in 1st line therapy will be included in this phase IV-study. Subject will receive a regimen of FOLFIRI in combination with Cetuximab every two weeks during study treatment phase. Treatment continues until

* disease progression
* complete response
* development of status of operability
* an uncontrollable exanthema grade 3 or 4 or
* intolerable toxicity is diagnosed. After study discontinuation or end of treatment, respectively, patients will be followed up until the the last patient was treated for 12 months and has completed the 36-months follow up phase. Tumor response will be evaluated (according to RECIST 1.1) every 12 weeks and at the end of study treatment

FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema

Non-randomized Phase-IV-study to Investigate the Efficacy of FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema

Progression-free survival rate at 12 months

Objective response rate over the entire treatment period

Duration until development of acneiforme follicular exanthema \>= grade 2 during treatment-phase

Development of paronychia during treatment-phase

Development of skin fissure (hand and foot) during treatment-phase

Rate of secondary resections of metastasis of liver with a curative approach during treatment-phase

Assessment of safety and tolerability during treatment phase

Development of acneiforme follicular exanthema \>= grade2 during treatment phase

Dr. Carl Schimanski

Principal Investigator

Symptoms and General Pathology

Carcinoma

Neoplastic Cells, Circulating

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasm Metastasis

Neoplastic Processes

Bevacizumab

Angiogenesis Inhibitors

Growth Inhibitors

* Bevacizumab 5 mg/kg iv, followed by
* Irinotecan 180 mg/m2 iv administered over a period of 30-90 minutes, followed by
* Leucovorin (LV) 400 mg/m2 iv administered over a period of 2 hours, followed by
* 5-FU 400 mg/m2 iv bolus, followed by
* 5-FU 2,400 mg/m2 for 46 h continuous infusion. This treatment will start on day 1 and will be repeated every 2 weeks (1 cycle).

FOLFIRI + bevacizumab

* Cetuximab in an initial 120-minute infusion on day 1 of 400 mg/m2, followed by 60-minute infusions of cetuximab at a dose of 250 mg/m2, once weekly
* FOLFIRI:

  * Irinotecan 180 mg/m2 iv administered over a period of 30-90 minutes, followed by
  * Leucovorin (LV) 400 mg/m2 iv administered over a period of 2 hours, followed by
  * 5-FU 400 mg/m2 iv bolus, followed by
  * 5-FU 2,400 mg/m2 for 46 h continuous infusion FOLFIRI will be given after the cetuximab infusion on day 1 of each period (every 2 weeks: 1 cycle).

FOLFIRI + cetuximab

Eduardo Díaz-Rubio, MD-PhD

Enrique Aranda, MD-PhD

Javier Sastre, MD-PhD

The purpose of the study is to explore the influence of BRAF and PIK3K status on the efficacy of FOLFIRI plus Bevacizumab or Cetuximab, as first line therapy of patients with RAS wild-type metastatic colorectal carcinoma and \< 3 circulating tumor cells

Influence of BRAF and PIK3K Status on the Efficacy of 5-Fluorouracil/Leucovorin/Oxaliplatin (FOLFIRI) Plus Bevacizumab or Cetuximab in Patients With RAS Wild-type Metastatic Colorectal Carcinoma and < 3 Circulating Tumor Cells (CTC)

Randomized Phase II Study to Explore the Influence of BRAF and PIK3K Status on the Efficacy of FOLFIRI Plus Bevacizumab or Cetuximab, as First Line Therapy of Patients With RAS Wild-type Metastatic Colorectal Carcinoma and < 3 Circulating Tumor Cells

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biomarker Directed Treatment in Metastatic Colorectal Cancer	NCT01703390	Metastatic Colo...	FOLFIRI + Cetux... modifiedFOLFOX6...	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema	NCT01315990	Colorectal Canc...	FOLFIRI + Cetux...	18 Years -	Johannes Gutenberg University Mainz
Biomarker Directed Treatment in Metastatic Colorectal Cancer	NCT01703390	Metastatic Colo...	FOLFIRI + Cetux... modifiedFOLFOX6...	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie
Influence of BRAF and PIK3K Status on the Efficacy of 5-Fluorouracil/Leucovorin/Oxaliplatin (FOLFIRI) Plus Bevacizumab or Cetuximab in Patients With RAS Wild-type Metastatic Colorectal Carcinoma and < 3 Circulating Tumor Cells (CTC)	NCT01640444	Colorectal Canc...	FOLFIRI + bevac... FOLFIRI + cetux...	18 Years - 70 Years	Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema	NCT01315990	Colorectal Canc...	FOLFIRI + Cetux...	18 Years -	Johannes Gutenberg University Mainz
Influence of BRAF and PIK3K Status on the Efficacy of 5-Fluorouracil/Leucovorin/Oxaliplatin (FOLFIRI) Plus Bevacizumab or Cetuximab in Patients With RAS Wild-type Metastatic Colorectal Carcinoma and < 3 Circulating Tumor Cells (CTC)	NCT01640444	Colorectal Canc...	FOLFIRI + bevac... FOLFIRI + cetux...	18 Years - 70 Years	Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Spots Global Cancer Trial Database for folfiri + cetuximab