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Capecitabine and Bevacizumab With Radiotherapy After 3-6 Months Chemotherapy for Patients With Oligometastatic Colorectal Cancer (OLGA Trial)

Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer, Metastases

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Trial Information

Capecitabine and Bevacizumab With Radiotherapy After 3-6 Months Chemotherapy for Patients With Oligometastatic Colorectal Cancer (OLGA Trial)

Combining chemoradiation with an antiangiogenic agent has a strong biological rationale, and
preclinical studies consistently show an increase in radiosensitization with combined
treatment. It is well described that hypoxia or HIF-1 expression is associated with a lower
radiation response and progression in solid tumors. Radiation itself induces transient tumor
hypoxia, which in turn stimulates VEGF production and VEGFR-2 expression what may also serve
as a paracrine proliferative stimulus that promotes out-of-field growth. The combination of
radiotherapy with an antiangiogenic agent (e.g. bevacizumab) thus offers the potential to
enhance the effect of radiation, and avoid further spread of disease. Furthermore, targeting
tumor vasculature improves the delivery of cytotoxic drugs (e.g. capecitabine) leading to
increased efficacy of chemoradiation. Combination with cytotoxic drugs could additionally
limit treatment-induced hypoxia (Senan and Smit 2007; Mazeron, Anderson et al. 2011).

Inclusion Criteria:

1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer

2. Oligometastatic disease, defined as at least one measureable lesion with size > 1cm
(RECIST v1.1) to a maximum of 3 sites and 5 lesions suitable for radiotherapy
according to the dose constraints for normal tissue

3. Patients being neither progressive nor resectable after 3-6 months of first line
chemotherapy (combination chemotherapy, at least chemo-doublet) 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 109/L, platelets ≥ 75 x109/L

9. INR < 1.5 within 7 days prior to starting study treatment. aPTT < 1.5 ULN within 7
days prior to starting study treatment

10. adequate liver function as measured by serum transaminases (AST & ALT) ≤ 5 x ULN and
a 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

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

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

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.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival rate

Outcome Description:

Progression free survival rate at 12 months after start of induction treatment (PFSR@12)

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Cordula Petersen, Prof.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Universitätsklinikum Hamburg-Eppendorf


Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

May 2013

Completion Date:

January 2018

Related Keywords:

  • Colorectal Cancer
  • Metastases
  • colorectal cancer
  • metastases
  • non resectable
  • chemoradiation
  • Colorectal Neoplasms
  • Neoplasm Metastasis