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

Charite Universitaetsmedizin Berlin KöR37 sites in 1 country153 target enrollmentOctober 16, 2024

DrugsLonsurf 20 mg/8.19 mg film-coated tablets Lonsurf 15 mg/6.14 mg film-coated tablets TRIFLUOROTHYMIDINE BEVACIZUMAB, BEVACIZUMAB Lonsurf 15 mg/6.14 mg film-coated tablets, Lonsurf 20 mg/8.19 mg film-coated tablets Vectibix 20 mg/ml concentrate for solution for infusion BEVACIZUMAB

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Charite Universitaetsmedizin Berlin KöR
Enrollment: 153
Locations: 37
Primary Endpoint: Objective response rate (ORR) according to RECIST 1.1 (assessment at the local trial center)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To compare the efficacy of treatment with trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab

Registry

euclinicaltrials.eu

Start Date

October 16, 2024

End Date

TBD

Last Updated

last year

Investigators

Sponsor

Charite Universitaetsmedizin Berlin KöR

Responsible Party

Principal Investigator

Sponsor Delegated Person

Scientific

Charite Universitaetsmedizin Berlin KöR

Eligibility Criteria

Inclusion Criteria

•Patient’s signed informed consent
•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.
•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.
•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 plus an additional contraceptive method that together result in a failure rate of <1% per year during the treatment period and for 6 months after the last dose of study treatment. In this regard, double barrier methods are not considered to have a failure rate of < 1%. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of study medication to avoid exposing the embryo. 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.
•Patients ≥ 18 years at the time of signing the informed consent
•Histologically confirmed adenocarcinoma of the colon or rectum (appendix carcinoma is excluded)
•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
•Metastases are primarily unresectable or patient is unable/unwilling to undergo surgery
•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.
•Patient is not eligible to undergo combination chemotherapy according to investigator’s assessment or unwilling to undergo combination chemotherapy.

Exclusion Criteria

•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
•History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or intra-abdominal abscess -unrelated to surgery- within 6 months prior to randomisation.
•Acute or subacute bowel obstruction, active chronic inflammatory bowel disease or chronic diarrhea
•History of keratitis, ulcerative keratitis or severe dry eye.
•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
•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 > 2 x 250 mg/day, clopidogrel > 75 mg/day, and cilostazol. Combination of these drugs are not allowed.
•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
•Core biopsy or other minor surgical procedure, excluding placement of a vascular access devices, within 3 days prior to the first dose of bevacizumab
•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
•Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.

Outcomes

Primary Outcomes

Objective response rate (ORR) according to RECIST 1.1 (assessment at the local trial center)

Secondary Outcomes

Overall survival (OS)
Progression-free survival (PFS)
Objective response rate (ORR) according to RECIST 1.1 (assessment by central review)
Depth of response (DpR) (assessment by central review)
Early tumor shrinkage ([ETS]; assessment by central review)
QoL as assessed with the QoL questionnaire EQ-5D-5L
Type, incidence, severity, and causal relationship to IMPs of non-serious adverse events and serious adverse events (severity evaluated according to CTCAE version 5.0)
Subsequent anti-tumor treatment lines (monotherapy and combination therapy treatment lines including medicinal products [chemotherapeutics, antibodies and targeted therapy] and investigator reported efficacy of subsequent treatment lines
Identification of biomarker for treatment efficacy and toxicity