Anti - EGFR therapy rechallenge in combination with chemotherapy in patients with advanced colorectal cancer.

Phase 1

Conditions: Therapeutic area: Diseases [C] - Cancer [C04]
RAS wild type advanced colorectal cancer
MedDRA version: 20.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2016-003644-37-CY

Lead Sponsor: Hellenic Cooperative Oncology Group (HeCOG)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 5

Inclusion Criteria

1.Signed and dated informed consent, and willing and able to comply with protocol requirements.
2.Histologically proven adenocarcinoma of the colon and/or rectum.
3.Metastatic disease confirmed clinically/radiologically.
4.Patients with Formalin-Fixed, Paraffin-Embedded (FFPE) tissue RAS wi ld type CRC at diagnosis, who had initial clinical benefit [complete response (CR), partial response (PR) or stable disease (SD)] during 1st line irinotecan-based or oxaliplatin-based chemotherapy in combination with cetuximab or panitumumab.
5.1st line treatment duration (FOLFIRI, FOLFOX + anti EGFR moAb, of whom at least 2/3 of cases being panitumumab) of at least 3 months.
6.2nd line therapy consisting of any chemotherapy (with or without Bevacizumab) definitely without anti-EGFR therapy of at least 2 months, followed by disease progression.
7.Eligible 3rd line regimens include FOLFIRI or Irinotecan or FOLFOX, according to standard practice and approved indications. It is required that the 3rd line regimen used will be different from the 2nd line and similar to the 1st line regimen.
8.At least one measurable or evaluable lesion as assessed by computed tomography (CT) scan or Magnetic Resonance Imaging (MRI) according to RECIST v1.1.
9.First course of treatment planned less than 1 week (7 days) after registration.
10.Age =18 years.
11.ECOG Performance status (PS) 0-2.
12.Adequate hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =9g/dL.
13.Adequate renal function: serum creatinine level <1.5 mg/dL and/or Glomelular Filtration Rate>50 mL/min by Cockroft/Gault formula.
14.Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline phosphatase, AST, ALT <5xULN.
15.Regular follow up feasible.
16.For female patients of childbearing potential, negative serum or urine pregnancy test within 1 week (7 days) prior of starting study treatment.
17.Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial.
18.Archival tumor tissue is required for exploratory research at enrolment.
19.Ability to undergo plasma sampling during the therapy course.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

1.Presence of CNS metastasis unless adequately treated (e.g. ineligible in the case of non irradiated CNS metastasis, seizures not controlled with standard medical therapy).
2.Active infection (ie, body temperature =38°C due to infection).
3.Intestinal obstruction, pulmonary fibrosis or interstitial pneumonitis, renal failure, liver failure, or cerebrovascular disorder.
4.Uncontrolled diabetes.
5.Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV within the last six months.
6.Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C.
7.Autoimmune disorders or history of organ transplantation that require immunosuppressive therapy.
8.Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years.
9.Major surgery or traumatic injury within the last 28 days.
10.Pregnant or breastfeeding women.
11.Patients with known allergy to any excipients to study drugs.
12.Other serious and uncontrolled chronic non-malignant disease.
13.Known dihydropyrimidine dehydrogenase (DPD) deficiency.
14.Palliative radiation therapy within 4 weeks prior to registration.
15.Life expectancy less than 12 weeks in the opinion of the Investigator.
16.Treatment with any other investigational medicinal product within 28 days prior to study entry.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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