JOURNAL ONKOLOGIE – STUDIE

MoLiMoR - A Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04554836

Studienbeginn:
Dezember 2020

Letztes Update:
19.01.2021

Wirkstoff:
Cetuximab

Indikation (Clinical Trials):
Adenocarcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
TheraOp

Collaborator:
-

Kontakt

Hanno Härtlein
Kontakt:
Phone: +49 641-94436-100
E-Mail: info@theraop.de» Kontaktdaten anzeigen

Studienlocations (3 von 8)

Universitätsklinikum Knappschaftskrankenhaus
Bochum
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Onkologisches Zentrum (Dachau II)
Dachau
(Bayern)
GermanyRekrutierend» Google-Maps

Onkologisches Zentrum - Krankenhaus Barmherzige Brüder Regensburg
Prüfeninger Straße 86
93049 Regensburg
(Bayern)
DeutschlandRekrutierend» Google-Maps

Kliniken-Essen-Mitte Evang. Huyssens-Stiftung
Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Brustzentrum am Klinikum Magdeburg
Birkenallee 34
39130 Magdeburg
DeutschlandRekrutierend» Google-Maps

Klinikum Oldenburg, Onkologie
Oldenburg
(Niedersachsen)
GermanyRekrutierend» Google-Maps

Brustzentrum Stuttgart am Marienhospital
Böheimstraße 37
70199 Stuttgart
DeutschlandRekrutierend» Google-Maps

Helios Dr. Horst Schmidt Kliniken
Wiesbaden
(Hessen)
GermanyRekrutierend» Google-Maps

Alle anzeigen

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

- Patients suitable for chemotherapy administration

- ECOG (Eastern Cooperative Oncology Group) status 0-1

- Consent to liquid biopsy and RAS 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

- 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

- 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

- Known dihydropyrimidine dehydrogenase (DPD) deficiency or 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 the start of the first line treatment in the study up to 24 months.):
Evaluation of efficacy in terms of progression free survival (PFS)

Secondary outcome:

1. Overall survival (OS) (Time Frame - From the start of the first line treatment in the study up to 24 months.):
In experimental and control arms

2. Time to failure of treatment strategy (TFTS) (Time Frame - From the start of the first line treatment in the study up to 24 months.):
In experimental and control arms

3. PFS (progression free survival) rate (Time Frame - 1 year after the start of the first line treatment.):
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 start of the first line treatment in the study up 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