JOURNAL ONKOLOGIE – STUDIE

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

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

Rekrutierend

NCT-Nummer:
NCT05007132

Studienbeginn:
Dezember 2021

Letztes Update:
15.02.2024

Wirkstoff:
Panitumumab 20 milligram/ML, Bevacizumab, Trifluridine/Tipiracil Hydrochloride

Indikation (Clinical Trials):
Colorectal Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Dominik Paul Modest

Collaborator:
-

Kontakt

Dominik Paul Modest, Prof.
Kontakt:
Phone: +49 30 450 553840
E-Mail: dominik.modest@charite.de» Kontaktdaten anzeigen

Sebastian Stintzing, Prof.
Kontakt:
Phone: +49 30 450 513002
E-Mail: sebastian.stintzing@charite.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Charité - Universitätsmedizin Berlin
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Modest Paul Modest, Prof.
Phone: +49 30 450 553840
E-Mail: dominik.modest@charite.de» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Patient's signed informed consent

2. Patients ≥ 18 years at the time of signing the informed consent

3. Histologically confirmed adenocarcinoma of the colon or rectum

4. 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

5. Metastases are primarily unresectable or patient is unable/unwilling to undergo

surgery

6. 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.

7. Patient is not eligible to undergo combination chemotherapy according to

investigator's assessment or unwilling to undergo combination chemotherapy.

8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

9. 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

- Urine dipstick for proteinuria < 2+ (within 14 days prior to randomisation),

unless a subsequent 24-hour urine collection demonstrates < 1 g of protein in 24

hours.

10. Patients without anticoagulation need to present with an INR <1.5 x ULN and partial

thromboplastin time (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 international normalized ratio (INR) and PTT are <1.5

x ULN..

11. 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.

12. 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.

Exclusion Criteria:

1. 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

2. 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.

3. 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

4. Transient ischaemic attack or cerebrovascular accident within 6 months prior to

randomization, history of cerebral or aortic aneurysm or dissection

5. 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.

6. Severe bleeding event within the last 6 months before randomisation (except tumor

bleeding surgically treated by tumor resection)

7. Evidence of bleeding diathesis or significant coagulopathy

8. Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or

diastolic ≥ 100 mm Hg under antihypertensive medication

9. Severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture.

10. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or

intra-abdominal abscess -unrelated to surgery- within 6 months prior to randomisation.

11. Acute or subacute bowel obstruction, active chronic inflammatory bowel disease or

chronic diarrhea

12. History of keratitis, ulcerative keratitis or severe dry eye.

13. 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

14. 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.

15. 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

16. Core biopsy or other minor surgical procedure, excluding placement of a vascular

access devices, within 3 days prior to the first dose of bevacizumab

17. 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

18. 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.

19. Medical history of other malignant disease than mCRC with the following exceptions:

- patients who have been disease-free for at least three years before randomisation

- patients with adequately treated and completely resected basal cell or squamous

cell skin cancer, in situ cervical, breast or prostate cancer, stage I uterine

cancer

- patients with any treated or untreated malignant disease that is associated with

a 5 year survival prognosis of ≥90% and does not require active therapy

20. Known alcohol or drug abuse

21. Pregnant or breastfeeding females

22. Participation in a clinical trial or experimental drug treatment within 28 days prior

to inclusion in the clinical trial or within a period of 5 half-lives of the

substances administered in a clinical trial or during an experimental drug treatment

prior to inclusion in the clinical trial, depending on which period is longest, or

simultaneous participation in another clinical trial while taking part in this

clinical trial.

23. Patient committed to an institution by virtue of an order issued either by the

judicial or the administrative authorities

24. Patient possibly dependent from the investigator including the spouse, children and

close relatives of any investigator

25. Limited legal capacity

Studien-Rationale

Primary outcome:

1. Objective response rate (Time Frame - 36 months):
Objective response rate according to RECIST 1.1

Secondary outcome:

1. Overall survival (Time Frame - 36 month):
time from randomization to date of death from any cause

2. Progression-free survival (Time Frame - 36 months):
time from randomization to progression of death from any cause

Studien-Arme

Experimental: Arm A
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
Active Comparator: Arm B
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

Geprüfte Regime

Panitumumab 20 milligram/ML:
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.
Bevacizumab:
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.
Trifluridine/Tipiracil Hydrochloride (Lonsurf):
Participants receive Trifluridine/tipiracil at 35 mg/m² BSA, twice daily, orally on days 1-5 and 8-12

Quelle: ClinicalTrials.gov

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