Rational Anti-EGFR therapy Selection for the first-line treatment of patients with metastatic KRAS/NRAS wild type colorectal cancer based on the use of molecular predictor miR-31-5p (RASmiR)
- Conditions
- inoperable, untreated, wild type RAS (wt KRAS/wtNRAS), metastatic colorectal cancer (mCRC)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001210-15-CZ
- Lead Sponsor
- Masarykuv onkologický ústav
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 375
1.The subject, prior to any study-related procedures, has provided Independent Ethics Committee approved written Informed Consent as per national regulations
2.The subject is male or female, aged 18 years or older.
3.The subject has histologically confirmed wild type KRAS and NRAS (at least in codons: 12, 13, 59, 61, 117, 146 / both genes) mCRC.
4.The subject has metastatic lesion measurable by RECIST 1.1.
5.The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and life expectancy > 3 months.
6. If subject is female of childbearing potential, subject has documentation of negative pregnancy test prior to enrollment.
7. Subject (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the ICF until at least 90 days after the last dose of systemic drugs.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75
1.The subject must not receive prior systemic anticancer treatment in adjuvant administration for colorectal cancer in the previous 6 months.
2.Disorders of intestinal patency:
a) Acute or sub-acute ileus
b) Therapy-insensitive diarrhea of grade G3 and above, especially due to short bowel syndrome
3.Patients who at the time of diagnosis of mCRC are indicated for surgical treatment, because their primary tumor and/or metastases are radically resectable.
4.The subject has primary Central Nervous System (CNS) malignancies or CNS metastases; exception: subjects with brain metastasis treated with radiotherapy or surgery will be allowed if their ECOG status is 0-1.
5.The subject has any of the following hematologic abnormalities:
•ANC 1,5 x 109/L
•Platelet count < 100 x 109/L
6.The subject has any of the following serum chemistry abnormalities:
•Total bilirubin > 2.5 x ULN
•Serum albumin < 20 g/L
•Calculated creatinine clearance < 30mL/min/1.73m2
•Proteinuria > 2+; protein greater than 2+ must have 24 hour urine collection
7.Cardiovascular disease limiting the overall condition of the patient (PS 2 and above): symptomatic heart failure, uncontrolled hypertension G2 and more (systole> = 140-159 mmHg / diastole> = 90-99 mmHg, or signs of hypertensive crisis), uncontrolled / symptomatic cardiac arrhythmia.
8.Acute thromboembolic disease or untreated and/or clinically symptomatic thromboembolic disease occurring 6 months before screening for the study
9.Significant bleeding disease of severity> G2 6 months before the first medication in the study.
10.Female subject is pregnant or lactating.
11.The subject has peripheral neuropathy > Grade 2.
12.The subject is participating in another interventional protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: •Progression-Free Survival (PFS) in patients with low verus high miR-31-5p expression: Compare the predictive value of miR-31-5p expression as measured progression free survival. PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed according to RECIST 1.1 or death due to any cause. Subjects who die without a reported prior progression will be considered to have progressed on the date of their death. Subjects who did not progress or die will be censored on the date of their last tumor assessment. Subjects who started any subsequent anti-cancer therapy without a prior reported progression will be censored.;Secondary Objective: •Progression-Free Survival (PFS) in all groups<br>•Overall Survival (OS) in all goups<br>•Overall Response Rate (ORR) in all groups;Primary end point(s): PFS A vs PFS B (PFS A > PFS B with = 25 %);Timepoint(s) of evaluation of this end point: with ending of follow-up period
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Median PFS in all groups<br>Median OS in all groups<br>Percentage of participants with an ORR in all groups;Timepoint(s) of evaluation of this end point: with ending of follow-up period