Safety and Efficacy Study of FOLFOX4+Panitumumab vs.FOLFIRI+Panitumumab in Subjects WT KRAS Colorectal Cancer and Liver-only Metastases

NCT00885885 | Completed Phase 2

• 2 other identifiers: TTD-08-04EudraCT: 2008-006766-28
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of the combination of Panitumumab with FOLFOX 4 Chemotherapy or Panitumumab with FOLFIRI Chemotherapy in Subjects with Wild- Type KRAS Colorectal Cancer and liver-only Metastases.

Conditions

Colorectal Cancer

Keywords

Colorectal Cancer; Panitumumab; FOLFOX-4; FOLFIRI

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  2009-2013

Secondary Outcomes (8)

• % of patients whose disease becomes resectable

  2009-2013

• Time to resection

  2009-2013

• Duration of response

  2009-2013

• Progression-free survival

  2009-2013

• Time to treatment failure

  2009-2013

Study Arms (2)

1

EXPERIMENTAL

Panitumumab+FOLFOX 4

Drug: Panitumumab+FOLFOX-4

2

EXPERIMENTAL

Panitumumab+FOLFIRI

Drug: Panitumumab+FOLFIRI

Interventions

Panitumumab+FOLFOX-4 DRUG

Panitumumab will be administered as a 60-minute ± 15 minutes IV infusion, just prior to administration of chemotherapy at a dose of 6 mg/kg on day 1 of each cycle. If the first infusion of panitumumab is well tolerated (without any serious infusion related reactions) all subsequent infusions may be administered over 30 minutes ± 10 minutes. A cycle of panitumumab is defined as 14 days. FOLFOX 4 chemotherapy will be administered on day 1 of each 14-day treatment cycle: * Oxaliplatin 85mg/m2 as a 120 minute infusion on day 1 of each cycle * Folinic acid 200mg/m2 as a 120 minute infusion on days 1 and 2 * A bolus (2 to 4 minutes) of 5-FU at 400mg/m2 on days 1 and 2 * 5-FU at 600mg/m2 as a continuous infusion of 22 hour infusion on days 1 and 2

1

Panitumumab+FOLFIRI DRUG

Panitumumab will be administered as a 60-minute ± 15 minutes IV infusion, just prior to administration of chemotherapy at a dose of 6 mg/kg on day 1 of each cycle. If the first infusion of panitumumab is well tolerated (without any serious infusion related reactions) all subsequent infusions may be administered over 30 minutes ± 10 minutes. A cycle of panitumumab is defined as 14 days. FOLFIRI chemotherapy will be administered on day 1 of each 14-day treatment cycle: * Irinotecan 180 mg/m2 will be administered over 90 minutes ± 15 minutes on day 1 of each cycle * Folinic acid 400 mg/m2 will be administered over 2 hours ± 15 minutes during the irinotecan infusion but without mixing * A bolus (2 to 4 minutes) of 5-FU at 400mg/m2 on day 1 * 5-FU at 2400 mg/m2 continuous intravenous infusion over 46-hour ± 2-hour on day 1 of each cycle.

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman \> 18 years \< 75 of age
• Competent to comprehend, sign, and date an IEC-approved informed consent form
• Histologically confirmed adenocarcinoma of the colon or rectum
• Wild Type KRAS status
• Metastatic colorectal carcinoma exclusively affecting only the liver, compliant with one of the following criteria
• Number of liver metastasis ≥ 4.
• Size of one liver metastasis \> 10 cm in diameter.
• Liver metastases technically not resectable.
• At least 1 uni-dimensionally measurable lesion
• Patients with the following characteristics will be included:
• Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with a disease-free interval \> than 6 months after its completion; or after oxaliplatin containing adjuvant treatment with a disease-free interval \> than 12 months
• Recurrence after surgical treatment and/or radiotherapy with no adjuvant systemic treatment.
• De novo diagnosis of the disease.
• Patients with simultaneous liver metastases are eligible, if the primary tumor has been resected at least 1 month prior chemotherapy.
• Prior radiotherapy is acceptable.

You may not qualify if:

• Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, erlotinib).Subjects who have experienced an infusion reaction to their first dose of anti-EGFR therapy (cetuximab) may participate in this clinical trial.
• Metastasis on any site other than the liver, including extrahepatic lymph nodes.
• Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive carcinoma of the skin.
• Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan
• Treatment for systemic infection within 14 days before initiating study treatment
• Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as \> 4 loose stools per day)
• History of Gilbert's syndrome or dihydropyrimidine deficiency
• History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results
• Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
• subject allergic to the ingredients of the study medication or to Staphylococcus protein A
• Any co-morbid disease that would increase risk of toxicity
• Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
• Any investigational agent within 30 days before enrolment
• Must not have had a major surgical procedure within 28 days of randomization

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Amgen: collaborator

Study Sites (1)

Spanish Cooperative Group for Gastrointestinal Tumour Therapy

Madrid, 28046, Spain

Location

Related Publications (2)

• Benavides M, Diaz-Rubio E, Carrato A, Abad A, Guillen C, Garcia-Alfonso P, Gil S, Cano MT, Safont MJ, Gravalos C, Manzano JL, Sanchez A, Alcaide J, Lopez R, Massuti B, Sastre J, Martinez E, Escudero P, Mendez M, Aranda E. Tumour location and efficacy of first-line EGFR inhibitors in KRAS/RAS wild-type metastatic colorectal cancer: retrospective analyses of two phase II randomised Spanish TTD trials. ESMO Open. 2019 Dec 1;4(6):e000599. doi: 10.1136/esmoopen-2019-000599. eCollection 2019.

  PMID: 31803504 DERIVED

• Carrato A, Abad A, Massuti B, Gravalos C, Escudero P, Longo-Munoz F, Manzano JL, Gomez A, Safont MJ, Gallego J, Garcia-Paredes B, Pericay C, Duenas R, Rivera F, Losa F, Valladares-Ayerbes M, Gonzalez E, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD). Eur J Cancer. 2017 Aug;81:191-202. doi: 10.1016/j.ejca.2017.04.024. Epub 2017 Jun 19.

  PMID: 28633089 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Albert Abad, MD, phD

  ICO-H. Germans Trial i Pujol. Badalona. Spain

  STUDY CHAIR

• Alfredo Carrato, MD, phD

  Hospial Ramón y Cajal. Madrid. Spain

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2009
• First Posted: April 22, 2009
• Study Start: May 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: August 1, 2017

Record last verified: 2017-07

Locations

ES (1)