A Phase II study to assess efficacy and safety of a combination chemotheraphy in first-line treatment with Xeloda + Oxaliplatin + Avastin or Xeloda + Irinotecan + Avastin. At progression of disease (second-line treatment) patient will receive Xeloda + Oxaliplatin + Avastin when received Xeloda + Irinotecan + Avastin in first-line or:At progression of disease (second-line treatment) patient will receive Xeloda + Irinotecan + Avastin if recieved Xeloda + Oxaliplatin + Avastin in first-line.

Phase 1

• Conditions: Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of metastases.Diagnosis of metastatic disease according to RECIST not more than 3 months prior to enrolmentNo prior chemotherapeutic treatment for metastatic colorectal carcinoma; MedDRA version: 18.1Level: LLTClassification code 10010028Term: Colorectal cancer Duke's DSystem Organ Class: 100000004864; MedDRA version: 18.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-002191-16-AT
• Lead Sponsor: Medizinische Universität Wien, Univ.Klink f. Innere Medizin I

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-06-21
• Study Completion: 2017-08-31
• Last Update Posted: 28 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1) Written informed consent
2) Age = 18 years
3) Patient must be able to comply with the protocol
4) Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of metastases.
5 )Diagnosis of metastatic disease according to RECIST not more than 3 months prior to enrolment.
6) Life Expectancy of at least 3 months
7) At least one measurable metastatic lesion (as per RECIST criteria)
8) Prior adjuvant or neo-adjuvant chemotherapy /radiotherapy allowed if completed more than 6 months before inclusion. Patients who received
Oxaliplatin for neoadjuvant or adjuvant treatment should receive XELIRI for 1st line treatment, patients who received Irinotecan for
neoadjuvant or adjuvant treatment should receive XELOX for 1st line treatment for their metastatic disease.
9) ECOG performance score of 0 or 1
10) Adequate haematological function: ANC = 1.5 x 109/L; platelets = 100 x 109/L, Hb = 9 g/dL
11) INR = 1.5 and aPTT = 1.5 x ULN within 7 days prior to starting study treatment
12) Adequate liver function: Serum bilirubin = 1.5 x ULN; alkaline phosphatase and transaminases = 2.5 x ULN (in case of liver metastases < 5 x ULN)
13) Serum Creatinine = 1.5 x ULN
14) Urine dipstick for proteinuria < 2+. If urine dipstick is = 2+, 24- hour urine must demonstrate = 1 g of protein in 24 hours
15) Negative serum pregnancy test within 7 days of starting study treatment in pre- menopausal women and women < 2 years after the onset of menopause. This test has to be reconfirmed by a urine test, should the 7 days window be exceeded. Fertile women (<2 years after last menstruation) and men must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile).

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 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1) Prior chemotherapeutic treatment for metastatic CRC
2) Symptomatic CNS metastases
3) Significant vascular disease (e.g. aortic aneurysm potentially requiring surgical intervention, pulmonary embolism or recent peripheral arterial thrombosis) within 6 months prior start of study treatment.
4) History of haemoptysis (= ½ teaspoon of bright red blood per episode) within 1 month prior start of study treatment
5) Past or current history (within the last 2 years prior to treatment start) of other malignancies (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).
6) Clinically significant cardiovascular disease, for example CVA (= 6 months before treatment start), myocardial infarction (= 6 months before treatment start), unstable angina, NYHA = grade 2 CHF, arrhythmia requiring medication, or uncontrolled hypertension.
7) Prior history of hypertensive crisis or hypertensive encephalopathy
8) Treatment with any other investigational agent or any other biological agent (e.g.cetuximab), or participation in another clinical trial within 30 days prior to entering this study.
9) Known hypersensitivity to any of the study drugs
10) Current or recent (within 10 days of first dose of study treatment) chronic use of aspirin (> 325 mg/day)
11) Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic (as opposed to prophylactic) purposes.
12) Evidence of bleeding diathesis or coagulopathy.
13) Serious, non healing wound, ulcer, or bone fracture.
14) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment, or anticipation of the need for major surgery during the course of the study. If CVAD is required for chemotherapy administration, it should be inserted within 2 days prior to study treatment cycle.
15) Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior start of study therapy
16) History of abdominal fistula, tracheo-oesophageal fistula or any grade 4 non gastrointestinal fistula, gastrointestinal perforation or intraabdominal abscess before 1st line therapy.
17) History or evidence upon physical/neurological examination of CNS disease (unrelated to cancer) (unless adequately treated with standard medical therapy) e.g. uncontrolled seizures
18) Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
19) Patients with contraindication for cross over chemotherapy (e.g. patients treated with irinotecan based first line therapy and serious polyneuropathy > grade 1, not feasible for oxaliplatin based cross over second line therapy, or patients treated with oxaliplatin based first line therapy and hereditary fructose intolerance not feasible for Irinotecan based cross over second line therapy)
20) Pregnancy or lactation
21) Fertile women (<2 years after last menstruation) and men not willing to use effective means of contraception.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified