Prospective, randomized, open, multicenter Phase II trial to investigate the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment of metastatic colorectal cancer: FIRE-8; AIO-KRK/YMO-0519
- Conditions
- Colon carzinomaC19Malignant neoplasm of rectosigmoid junction
- Registration Number
- DRKS00027086
- Lead Sponsor
- Charité Universitätsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 153
1. Patient’s signed informed consent
2. Patients = 18 years at the time of signing the informed consent
3. Histologically confirmed adenocarcinoma of the colon or rectum
4. Metastatic colorectal cancer (mCRC) with at least one measurable lesion according to
RECIST 1.1 in a computed tomography (CT) or magnetic resonance imaging (MRI)
scan performed within 5 weeks prior to randomisation
5. Metastases are primarily unresectable or patient is unable/unwilling to undergo surgery
6. RAS wild-type (KRAS, exons 2, 3, 4 and NRAS, exons 2, 3, 4) mCRC, proven in the
primary tumor or metastasis. The RAS mutational status must be determined by
means of a validated test method.
7. Patient is not eligible to undergo combination chemotherapy according to
investigator’s assessment or unwilling to undergo combination chemotherapy.
8. ECOG performance status 0-2
9. Adequate bone marrow, hepatic and renal organ function, defined by the following
laboratory test results:
? Absolute neutrophil count =1.5 x 10
9
/L (1500/µL)
? Hemoglobin = 80 g/L (8 g/dL)
? Platelet count = 75 x10
9
/L (75,000/µL) without transfusion
? Total serum bilirubin of = 1.5 x upper limit of normal (ULN)
? Aspartate aminotransferase (AST/GOT) and alanine aminotransferase
(ALT/GPT) = 2.5 × ULN; if liver function abnormalities are due to underlying
liver metastasis, AST and ALT = 5 × ULN
? Calculated glomerular filtration rate (GFR) according to Cockcroft –Gault
formula or according to MDRD = 30 mL/min or serum creatinine = 1.5 x ULN
? Urine dipstick for proteinuria < 2+ (within 14 days prior to randomisation), unless
a subsequent 24-hour urine collection demonstrates < 1 g of protein in 24 hours.
10. Patients without anticoagulation need to present with an INR <1.5 x ULN and PTT
<1.5 x ULN. Patients with anticoagulation may be enrolled if the patient receives the
medication at a stable dose for at least 2 weeks before randomisation and provided
that INR and PTT are <1.5 x ULN.
11. For females of childbearing potential (FCBP): negative pregnancy test within 14 days
before randomisation and agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive methods with a failure rate of <1% per year during
the treatment period and for at least 6 months after the last dose of study treatment.
A woman is considered to be of childbearing potential if she is postmenarcheal, has
not reached a postmenopausal state (= 12 continuous months of amenorrhea with no
identified cause other than menopause), and has not undergone surgical sterilization
(removal of ovaries and/or uterus). Examples of contraceptive methods with a failure
rate of < 1% per year include bilateral tubal ligation, male partner’s sterilization,
hormonal contraceptives that inhibit ovulation supplemented with a barrier method, hormone-releasing intrauterine devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical trial and the preferred and usual lifestyle of the patient. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception.
12. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as
defined below:
With female partners of childbearing potential, men must remain abstinent or use a
condom
1. Prior systemic therapy of metastatic disease.
Note: Prior adjuvant chemotherapy is permitted, if completed > 3 months prior to
randomisation. Multimodal treatment of rectal cancer is not considered anti-metastatic
therapy and does not preclude study participation
2. Known brain metastasis. In case of symptoms that are suggestive of brain metastasis,
brain metastasis has to be ruled out by means of cranial CT/MRI.
3. Significant cardiovascular disease such as: New York Heart Association Class III or
greater heart failure; myocardial infarction within 6 months prior to randomisation; balloon
angioplasty (PTCA) with or without stenting within 6 months prior to randomisation;
despite anti-arrhythmic therapy unstable cardiac arrhythmia > grade 2 NCI CTCAE;
unstable angina pectoris
4. Transient ischaemic attack or cerebrovascular accident within 6 months prior to
randomization, history of cerebral or aortic aneurysm or dissection
5. Medical history of deep vein thrombosis or pulmonary embolism within 6 months prior to
randomisation or medical history of recurrent thromboembolic events (> 1 episode of
deep vein thrombosis, pulmonary embolism, peripheral embolism) within the last 2 years.
6. Severe bleeding event within the last 6 months before randomisation (except tumor
bleeding surgically treated by tumor resection)
7. Evidence of bleeding diathesis or significant coagulopathy
8. Uncontrolled hypertension defined as systolic blood pressure =160 mm Hg and/or
diastolic = 100 mm Hg under antihypertensive medication
9. Severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture.
10. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or
intra-abdominal abscess -unrelated to surgery- within 6 months prior to randomisation.
11. Acute or subacute bowel obstruction, active chronic inflammatory bowel disease or
chronic diarrhea
12. History of keratitis, ulcerative keratitis or severe dry eye.
13. Hypersensitivity to trifluridine/tipiracil or panitumumab or bevacizumab or any of the
excipients, known hypersensitivity to Chinese hamster ovary cell products, known
hypersensitivity to human or humanized antibodies
14. Current or recent (within 10 days of randomisation) use of or anticipated need for
continuous treatment during study treatment with acetylsalicylic acid > 325 mg/day or
treatment with dipyramidole, ticlopidine > 2x250 mg/day, clopidogrel > 75 mg/day, and
cilostazol. Combination of these drugs are not allowed.
15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to randomisation, or abdominal surgery, abdominal interventions or significant
abdominal traumatic injury within 28 days prior to randomisation or anticipation of need
for major surgical procedure during the course of the study or non-recovery from side
effects of any such procedure
16. Core biopsy or other minor surgical procedure, excluding placement of a vascular
access devices, within 3 days prior to the first dose of bevacizumab
17. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis/interstitial pneumonia, or idiopathic
pneumonitis/interstitial pneumonia, or evidence of active pneumonitis or pulmonary
fibrosis on screening chest imaging
18. Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use o
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate according to RECIST 1.1, Restaging will be performed every ten weeks
- Secondary Outcome Measures
Name Time Method Overall survival, Progression-free survival, Objective response rate according to RECIST 1.1 performed evry ten weeks; Depth of response, Early tumor shrinkage; Quality of life as assessed with QoL, Identification of biomarker for treatment efficacy and toxicity