Clinical trial NCT00958386: Safety and Efficacy Study of Panitumumab+Irinotecan in Patients Wild-Type (WT) KRAS Metastatic Colorectal Cancer Refractory to Irinotecan Based Chemotherapy (SPECTRA)
Official title: Open, Multicenter Phase II Study to Evaluate the Efficacy and Safety of the Combination of Panitumumab With Irinotecan in Patients With Wild-Type KRAS Metastatic Colorectal Cancer Refractory to Irinotecan Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: colorectal cancer
Panitumumab
irinotecan
Lead sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2009-08-13
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy and safety of the combination of Panitumumab with Irinotecan in patients with Wild-Type KRAS metastatic colorectal cancer refractory to irinotecan based chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Competent to comprehend, sign, and date an IEC-approved informed consent form.
* Men or women 18 years of age or older at the time the written informed consent is obtained.
* Histologically confirmed metastatic adenocarcinoma of the colon or rectum
* Wild-Type KRAS (No mutation) by allelic discrimination on tumor DNA.
* Karnofsky performance status ≥ 70% at the time of enrolment in the study.
* Within seven days prior to initiating study treatment:

  * Adequate bone marrow function: neutrophils ≥ 1.5x109/ L; platelets ≥ 100x109/L; hemoglobin ≥ 9g/dL.
  * Hepatic functions as follows: total bilirubin count ≤ 1.5 x ULN; ALAT and ASAT ≤ 2.5 x ULN (≤5 x ULN in case of liver metastasis).
  * Renal function: serum creatinine ≤1.5 ULN
  * Metabolic functions: magnesium ≥ lower limit of normal (LLN), calcium ≥ lower limit of normal (LLN)
* Life expectancy ≥ 3 months.

Exclusion Criteria:

* Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive cervical cancer.
* Unresolved toxicities from prior systemic therapy that, in the opinion of the investigator, does not qualify the patient for inclusion.
* Documented or suspected central nervous system metastases.
* Hormonal therapy, immunotherapy or experimental or approved proteins/antibodies (eg, Bevacizumab) ≤ 30 days before inclusion.
* Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
* Prior anti-EGFr antibody therapy (eg, Cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, Erlotinib) or EGFR signal transduction inhibitors. Subjects who discontinue their first dose of anti-EGFR therapy (Cetuximab) because of an infusion reaction may participate in this clinical trial.
* Paraffin-embedded tissue or unstained tumor slides from primary or metastatic tumor not available (blocks available for Translational research).
* 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.
* Acute or sub-acute intestinal occlusion and /or 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, and 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 initiation of the treatment.
* Subject who is pregnant or breast feeding.
* Surgery (excluding diagnostic biopsy or central venous catheter placement) and/or radiotherapy within 28 days prior to initiation of study treatment.
* Woman or man of childbearing potential not consenting to use adequate contraceptive precautions i.e. double barrier contraceptive methods (e.g. diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men.
* Subject unwilling or unable to comply with study requirements.
* Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Primary outcomes:
measure: Objective response rate
timeFrame: 2009-2012
Secondary outcomes:
measure: disease control rate
timeFrame: 2009-2012
measure: duration of response
timeFrame: 2009-2012
measure: time to progression
timeFrame: 2009-2012
measure: time to response
timeFrame: 2009-2012
measure: time to treatment failure
timeFrame: 2009-2012
measure: duration of stable disease
timeFrame: 2009-2012
measure: Progression free survival
timeFrame: 2009-2012
measure: Overall survival
timeFrame: 2009-2012
measure: Safety profile
timeFrame: 2009-2012
measure: Evaluation of molecular predictive markers
timeFrame: 2009-2012
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Spanish Cooperative Group for Gastrointestinal Tumour Therapy
Study officials:
affiliation: Hospital Vall de Hebrón. Barcelona. Spain
name: Josep Tabernero, MD, phD
role: STUDY_CHAIR
affiliation: Hospital Reina Sofía. Cordoba. Madrid
name: Enrique Aranda, MD; phD
role: STUDY_CHAIR
References: