E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients neither being progressive nor resectable after 3-6 months chemotherapy for oligometastatic (up to 3 lesions/5 sites) colorectal cancer |
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E.1.1.1 | Medical condition in easily understood language |
Patients neither being progressive nor resectable after 3-6 months chemotherapy for oligometastatic colorectal cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy of chemoradiation with capecitabine and bevacizumab in oligometastatic patients with colorectal cancer neither being progressive nor resectable after chemotherapy in terms of progression free survival. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are safety and tolerability of the treatment as well as time to progression within and outside the irradiated area, overall survival, quality of life, and overall response rate (according to RECIST v1.1). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer 2) Oligometastatic disease, defined as at least one measurable lesion with size > 1 cm to a maximum of 3 sites and 5 lesions. (RECIST v1.1) 3) Patients being neither progressive nor resectable after 3-6 months of first line chemotherapy with bevacizumab. 4) Maximum treatment interruption after induction therapy of 6 weeks 5) ECOG Performance status ≤ 1 6) Life expectancy > 3 months 7) Age ≥18 years. 8) Haematologic function: ANC ≥ 1.5 x 10^9/L, platelets ≥ 75 x 10^9/L 9) INR <1.5 within 7 days prior to starting study treatment. aPTT < 1.5 x ULN within 7 days prior to starting study treatment. 10) Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 5 x ULN and total bilirubin ≤ 1.5 x ULN 11) Adequate renal function: Serum creatinine ≤ 1.5 x ULN 12) Signed, written informed consent 13) Ability to swallow tablets |
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E.4 | Principal exclusion criteria |
1) Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study. 2) Prior radiotherapy for metastatic lesions (prior radiotherapy for primary tumor allowed if followed by complete resection and no sign for local recurrence at the time of enrolment). 3) Pre History or evidence upon physical/neurological examination of CNS disease (unrelated to cancer) (unless adequately treated with standard medical therapy) e.g. uncontrolled seizures. 4) Fertile women (< 2 years after last menstruation) and women of childbearing potential unwilling or unable to use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel or surgically sterile). 5) Pregnancy or lactation. 6) Positive serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 2 years after the onset of menopause. Note: a negative test has to be reconfirmed by a urine test, should the 7-day window be exceeded. 7) Past or current history (within the last 2 years prior to treatment start) of other malignancies except metastatic colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible). 8) Known DPD-insufficiency 9) Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > 4 loose stools per day) 10) Serious, non-healing wound, ulcer or bone fracture. 11) Evidence of bleeding diathesis or coagulopathy. 12) Urine dipstick for proteinuria ≥2+. If urine dipstick is ≥ 2+, 24-hour urine must demonstrate ≤ 1 g of protein in 24 hours for patient to be eligible. 13) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to first treatment with study medication. 14) Clinically significant cardiovascular disease, for example CVA, myocardial infarction (≤ 12 months before treatment start), unstable angina pectoris, NYHA Class II CHF, arrhythmia requiring medication, or uncontrolled hypertension. 15) 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. 16) Concomitant therapy with sorivudin or chemical analogues like brivudin 17) Known hypersensitivity or contraindication to the drugs used in the trial (eg: capecitabine, bevacizumab) 18) Inability or unwillingness to comply with the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival rate at 12 months after start of induction treatment (PFSR@12) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after start of induction treatment |
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E.5.2 | Secondary end point(s) |
• Progression free survival (PFS) • Time to progression (TTP) in 2 cohorts: a) regards only progression within (TTPir) and b) in- and outside irradiated areas (“overall” TTP) • Overall survival (OS) • Efficacy of the investigational therapy shown by the Overall Response Rate (CR and PR) • Safety, Quality of life (QoL) • Prognostic and predictive value of PET scan at baseline and at 2 months after chemoradiation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 months after start of induction treatment 12 months after start of induction treatment 5 years after start of induction treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Study completion will be assessed by clinical visit and/or telephone follow-up for up to five years after last patient out.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |