JOURNAL ONKOLOGIE – STUDIE
MoLiMoR - A Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab
Rekrutierend
NCT-Nummer:
NCT04554836
Studienbeginn:
Dezember 2020
Letztes Update:
29.04.2021
Wirkstoff:
Cetuximab
Indikation (Clinical Trials):
Adenocarcinoma
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 2
Sponsor:
TheraOp
Collaborator:
-
Kontakt
Kontakt:
Phone: +49 641-94436-100
E-Mail: info@theraop.de» Kontaktdaten anzeigen
Studienlocations
(3 von 20)
Bochum
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Coburg
(Bayern)
GermanyRekrutierend» Google-Maps
Dachau
(Bayern)
GermanyRekrutierend» Google-Maps
Dessau
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
Prüfeninger Straße 86
93049 Regensburg
(Bayern)
DeutschlandRekrutierend» Google-Maps
Dortmund
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Beurhausstraße 40
44137 Dortmund
DeutschlandRekrutierend» Google-Maps
Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Frankfurt (Oder)
(Brandenburg)
GermanyRekrutierend» Google-Maps
Alte Rothenfelder Straße 23
49124 Georgsmarienhütte
DeutschlandRekrutierend» Google-Maps
4103 Leipzig
DeutschlandRekrutierend» Google-Maps
Lübeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Birkenallee 34
39130 Magdeburg
DeutschlandRekrutierend» Google-Maps
Minden
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Oldenburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Südring 81
18059 Rostock
DeutschlandRekrutierend» Google-Maps
Böheimstraße 37
70199 Stuttgart
DeutschlandRekrutierend» Google-Maps
Wiesbaden
(Hessen)
GermanyRekrutierend» Google-Maps
Feldkirch
AustriaRekrutierend» Google-Maps
Studien-Informationen
Brief Summary:This is an open-label, prospective, randomized, multicenter phase II trial that will evaluate
the efficacy and safety of intermittent addition of cetuximab to a FOLFIRI-based first line
therapy to patients with RAS (Rat sarcoma)-mutant mCRC (Metastatic colorectal cancer)
diagnosis who convert to RAS wild-type using monitoring of the RAS mutation status by liquid
biopsy.
Ein-/Ausschlusskriterien
Inclusion Criteria:- Histologically confirmed, UICC stage IV adenocarcinoma of the left-sided colon or
rectum with metastases (metastatic colorectal cancer), primarily non-resectable,
confirmed RAS mutations proven in the primary tumor or metastasis (KRAS ans NRAS exon
2, 3, 4)
- Age ≥ 18 years on day of signing informed consent
- No previous chemotherapy for metastatic disease (1- 2 cycles FOLFIRI or mFOLFIRI are
permitted before enrolment until RAS status is determined)
- Patients suitable for chemotherapy administration
- ECOG (Eastern Cooperative Oncology Group) status 0-1
- Consent to liquid biopsy and mutation analysis
- Estimated life expectancy > 3 months
- Presence of at least one measurable reference lesion according to the RECIST 1.1
criteria (chest CT and abdominal CT 4 weeks or less before enrollment)
- Adequate bone marrow function defined as: Leukocytes 3.0 x 10 9/L with neutrophils 1.5
x 10 9/L, Thrombocytes 100 x 10 9/L, Hemoglobin 9 g/dL
- Adequate hepatic function defined as: Serum bilirubin 1.5 x ULN (Upper limit of
normal), ALAT (Alanine-aminotransferase (= SGPT = serum glutamate pyruvate
transaminase) and ASAT (aspartate-aminotransferase (= SGOT = serum glutamate
oxalacetate transaminase) 2.5 x ULN (Upper limit of normal) (in the presence of
hepatic metastases, ALAT and ASAT 5 x ULN)
- Adequate renal function: Creatinine clearance ≥ 50 mL/min
- Adequate cardiac function defined as Normal ECG and echocardiogram with a left
ventricular ejection fraction (LVEF) of 55%
- INR (International normalized ratio) < 1.5 and aPTT (activated Partial thromboplastin
time) < 1.5 x ULN (patients without anticoagulation). Therapeutic anticoagulation is
allowed if INR and aPTT have remained stable within the therapeutic range for at least
2 weeks.
- Time interval of at least 6 months since last administration of any previous
neoadjuvant/adjuvant chemotherapy or radiochemotherapy of the primary tumor in
curative treatment intention to start of 1st line treatment
- Any relevant toxicities of prior treatments must have resolved to grade ≤ 1 according
to the CTCAE (version 5), except alopecia
- Women of childbearing potential (WOCBP) should have a negative urine pregnancy test
within 72 hours prior to receiving the first dose of study medication.
- Highly effective contraception for both male and female patients throughout the study
and for at least 3 months after last dose of study medication administration if the
risk of conception exists. Highly effective contraception has to be in line with the
definition of the CTFG (Clinical Trial Facilitation Group) recommendation
- Signed written informed consent and capacity of understanding the informed consent
Exclusion Criteria:
- Right sided mCRC
- Primarily resectable metastases
- Previous chemotherapy for the colorectal cancer with the exception of adjuvant
treatment, completed at least 6 months before entering the study (1- 2 cycles FOLFIRI
or mFOLFIRI are permitted before enrolment)
- Patients with known brain metastases
- Symptomatic peritoneal carcinosis
- Progressive disease before randomization
- History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune
colitis or chronic diarrhea
- Grade II heart failure (NYHA classification), Myocardial infarction, balloon
angioplasty (PTCA) with or without stenting, and cerebral vascular accident/stroke
within the past 12 months before enrollment, unstable angina pectoris, serious cardiac
arrhythmia according to investigator's judgment requiring medication
- Active infection with hepatitis B or C
- Medical or psychological impairments associated with restricted ability to give
consent or not allowing conduct of the study
- Additional cancer; Exceptions include adequately treated basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has
undergone potentially curative therapy without evidence of recurrence
- Uncontrolled hypertension
- Marked proteinuria (nephrotic syndrome)
- Arterial thromboembolism or severe hemorrhage within 6 months prior to randomization
(with the exception of tumor bleeding before tumor resection surgery)
- Hemorrhagic diathesis or tendency towards thrombosis
- Participation in a clinical study or experimental drug treatment within 30 days prior
to study
- Known hypersensitivity or allergic reaction to any of the study medications
- Severe, non-healing wounds, ulcers, bone fractures or an infection requiring systemic
therapy
- Known history of alcohol or drug abuse
- Complete dihydropyrimidine dehydrogenase (DPD) deficiency (phenotype and/or genotype
test) (Patients with partial DPD deficiency may be included in this clinical trial at
the discretion of the investigator and should receive a reduced starting 5-FU dose)
- Known glucuronidation deficiency (Gilbert's syndrome) (specific screening not
required)
- Absent or restricted legal capacity
- For female patients only: Pregnancy (absence to be confirmed by ß-HCG test) or
lactating
Studien-Rationale
Primary outcome:1. Progression free survival (PFS) (Time Frame - From date of randomization up to 24 months):
Evaluation of efficacy in terms of progression free survival (PFS)
Secondary outcome:
1. Overall survival (OS) (Time Frame - From date of randomization up to 24 months.):
In experimental and control arms
2. Time to failure of treatment strategy (TFTS) (Time Frame - After randomization up to 24 months.):
In experimental and control arms
3. PFS (progression free survival) rate (Time Frame - 1 year after date of randomization):
In experimental and control arms
4. Depth of response (Time Frame - From the start of the first line treatment in the study up to 24 months.):
In terms of reduction of tumor mass in experimental and control arms
5. Metastasis resections. (Time Frame - From the start of the first line treatment in the study up to 24 months.):
In experimental and control arms.
6. Objective response rate (ORR) (Time Frame - From the start of the first line treatment in the study up to 24 months.):
Defined as patients with partial or complete response (CR or PR) in experimental and control arms
7. Safety profile (Time Frame - From the date of signature of Informed Consent to 24 months.):
According to CTCAE (Common Terminology Criteria of Adverse Events), Version 5.0 criteria in experimental and control arms.
8. Identification of driver mutations. (Time Frame - From the start of the first line treatment in the study up to 24 months.):
In patients with progressive disease (PD) under cetuximab therapy who remain RAS (Rat sarcoma) wild-type in liquid biopsy.
9. Comparison the efficacy in terms of progression free survival (PFS) (Time Frame - From the start of the first line treatment in the study up to 24 months.):
In patients with conversion to RAS (RAt sarcoma) wild-type in both ddPCR (Droplet Digital PCR) BEAMing with those patients showing conversion to RAS wild-type in ddPCR but not in BEAMing.
Studien-Arme
- Experimental: FOLFIRI + cetuximab
Patients in Arm A will receive FOLFIRI + cetuximab until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first. The recurrence of RAS-mutation without PD to switch back to FOLFIRI. In case of repeated conversion to RAS wild-type without PD, treatment will shift to FOLFIRI + cetuximab again, and so on. Switches of treatment will proceed until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first. [FOLFIRI = Irinotecan, Folinic acid (racemic), Fluorouracil (5-FU)] - Other: FOLFIRI
Patients in Arm B will continue therapy with FOLFIRI until PD, unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first.
Geprüfte Regime
- Cetuximab:
Patients in Arm A will receive FOLFIRI +cetuximab. - FOLFIRI:
Irinotecan, Folinic acid (racemic), Fluorouracil (5-FU)
Quelle: ClinicalTrials.gov
Das könnte Sie auch interessieren
