Trifluridine/ Tipiracil Plus Panitumumab Versus Trifluridine/ Tipiracil Plus Bevacizumab as First-line Treatment of Metastatic Colorectal Cancer

NCT05007132 | Recruiting Phase 2 DMC

• 2 other identifiers: FIRE-82019-004223-20
• Study Type: interventional
• Target: 153
• Locations: 1 country
• Sites: 1

Brief Summary

FIRE-8 is a prospective, randomized, open label, multicenter phase II clinical trial. To evaluate the effecacy of trifluridine / tipiracil and panitumumab (Arm A) compared to trifluridine / tipiracil and bevacizumab (Arm B), participants will be randomly assigned to either Arm A or Arm B for the treatment of metastatic colorectal cancer. The primary objectives of this study is to compare the effecacy of treatment with trifluridine / tipiracil plus panitumumab versus trifluridine / tipiracil plus bevacizumab.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response rate according to RECIST 1.1

  36 months

Secondary Outcomes (2)

• Overall survival

  36 month

• Progression-free survival

  36 months

Study Arms (2)

Arm A

EXPERIMENTAL

Trifluridine/tipiracil, 35 mg/m² body surface area (BSA), twice daily, orally on days 1-5 and 8-12 Panitumumab at 6 mg/kg bodyweight, intravenous infusion on days 1 and 15

Biological: Panitumumab 20 milligram/ML; Drug: Trifluridine/Tipiracil Hydrochloride

Arm B

ACTIVE COMPARATOR

Trifluridine/tipiracil, 35 mg/m² body surface area, twice daily, orally on days 1-5 and 8-12 Bevacizumab at 5 mg/kg bodyweight, intravenous infusion on days 1 and 15

Biological: Bevacizumab; Drug: Trifluridine/Tipiracil Hydrochloride

Interventions

Panitumumab 20 milligram/ML BIOLOGICAL

Participants receive Panitumumab at 6mg/ kg intravenously (IV) on Day 1 and 15 of each 28-day cycle. Treatment is continued until occurrence of progression according to RECIST 1.1 criteria as evaluated by the investigator or unacceptable toxicity.

Arm A

Bevacizumab BIOLOGICAL

Participants receive bevacizumab at 5 mg/ kg intravenously (IV) on Day 1 and 15 of each 28-day cycle. Treatment is continued until occurrence of progression according to RECIST 1.1 criteria as evaluated by the investigator or unacceptable toxicity.

Arm B

Trifluridine/Tipiracil Hydrochloride DRUG

Participants receive Trifluridine/tipiracil at 35 mg/m² BSA, twice daily, orally on days 1-5 and 8-12

Also known as: Lonsurf

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient's signed informed consent
• Patients ≥ 18 years at the time of signing the informed consent
• Histologically confirmed adenocarcinoma of the colon or rectum
• 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 (Rat Sarcoma) wild-type (Kirsten rat sarcoma (KRAS), exons 2, 3, 4 and Neuroblastoma RAS viral oncogene homologue (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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate bone marrow, hepatic and renal organ function, defined by the following laboratory test results:
• Absolute neutrophil count ≥ 1.5 x 109/L (1500/μL)
• Hemoglobin ≥ 80 g/L (8 g/dL)
• Platelet count ≥ 75 x109/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 formula ≥ 30 mL/min or serum creatinine ≤ 1.5 x ULN

You may not qualify if:

• 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 antimetastatic therapy and does not preclude study participation
• 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.
• 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
• Transient ischaemic attack or cerebrovascular accident within 6 months prior to randomization, history of cerebral or aortic aneurysm or dissection
• 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.
• Severe bleeding event within the last 6 months before randomisation (except tumor bleeding surgically treated by tumor resection)
• Evidence of bleeding diathesis or significant coagulopathy
• Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or diastolic ≥ 100 mm Hg under antihypertensive medication
• Severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture.
• 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

Sponsors & Collaborators

• Dominik Paul Modest: lead

Study Sites (1)

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Related Publications (1)

• Sommerhauser G, Kurreck A, Stintzing S, Heinemann V, von Weikersthal LF, Dechow T, Kaiser F, Karthaus M, Schwaner I, Fuchs M, Konig A, Roderburg C, Hoyer I, Quante M, Kiani A, Fruehauf S, Muller L, Reinacher-Schick A, Ettrich TJ, Stahler A, Modest DP. Study protocol of the FIRE-8 (AIO-KRK/YMO-0519) trial: a prospective, randomized, open-label, multicenter phase II trial investigating the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer. BMC Cancer. 2022 Jul 27;22(1):820. doi: 10.1186/s12885-022-09892-8.

  PMID: 35897060 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Trifluridine; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Dominik Paul Modest, Prof.

CONTACT

+49 30 450 553840; dominik.modest@charite.de

Sebastian Stintzing, Prof.

CONTACT

+49 30 450 513002; sebastian.stintzing@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: Prospective, randomized, open, multicenter Phase II trial with two parallel arms

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 16, 2021
• Study Start: December 17, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2032
• Last Updated: February 15, 2024

Record last verified: 2024-02

Locations

DE (1)