nresectable metastatic colorectal cancer Colorectal cancer, Unresectable colorectal cancer, Advanced colorectal cancer, Recurrent colorectal cancer, Metastatic colorectal cancer, FTD/TPI, Trifluridine/tipiracil, Fruquintinib, Phase I clinical trial, Dose-limiting toxicity
Conditions
Interventions
To administer combination therapy with trifluridine/tipiracil and fruquintinib.
D000077324/D000086002
Trifluridine/tipiracil, FTD/TPI, Fruquintinib, Combination therapy, Oral chemotherapy, Anti-angiogenic agent
Sponsors
Shinozaki Eiji
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient has been histologically diagnosed based on a surgical or biopsy specimen with adenocarcinoma as defined in the Japanese Classification of Colorectal Carcinoma 9th Edition including papillary adenocarcinoma tubular adenocarcinoma poorly differentiated adenocarcinoma mucinous carcinoma signet ring cell carcinoma or medullary carcinoma. 2. The primary tumor is located in the cecum C ascending colon A transverse colon T descending colon D sigmoid colon S rectosigmoid RS upper rectum Ra or lower rectum Rb. 3. The patient has been diagnosed with unresectable Stage IV or recurrent colorectal cancer based on contrast enhanced CT of the chest abdomen and pelvis. If contrast enhanced CT cannot be performed due to contrast allergy renal dysfunction or bronchial asthma non contrast CT is acceptable. 4. The patient is 18 years of age or older at the time of registration. 5. The patient has an ECOG performance status of 0 or 1. 6. The patient has measurable disease. 7. The patient has received at least one prior regimen of standard systemic therapy for colorectal cancer and is refractory or intolerant to such therapy. Standard systemic therapy includes fluoropyrimidine oxaliplatin and irinotecan and at least one anti angiogenic agent such as bevacizumab ramucirumab or aflibercept. For RAS wild type tumors at least one anti EGFR antibody such as cetuximab or panitumumab is required. For BRAF V600E mutant tumors one BRAF inhibitor and one anti EGFR antibody with or without a MEK inhibitor are required. For MSI high tumors one immune checkpoint inhibitor such as pembrolizumab or nivolumab is required. For HER2 positive tumors both trastuzumab and pertuzumab are required. Perioperative systemic therapy is considered ineffective if recurrence or progression occurs during treatment or within 6 months after the final dose and is counted as first line therapy. Intolerance to perioperative therapy is defined regardless of the interval between the last dose and recurrence or progression. 8. The patient has no prior treatment with FTD TPI regorafenib or fruquintinib. 9. The patient is able to take oral medications. 10. The patient has not undergone surgery requiring general anesthesia within 28 days prior to registration. For stoma creation registration is allowed if at least 14 days have elapsed after surgery. 11. Laboratory values obtained within 7 days prior to registration meet all of the following criteria absolute neutrophil count greater than or equal to 1500 per mm3 hemoglobin greater than or equal to 8.0 g per dL with no blood transfusion within 14 days platelet count greater than or equal to 100000 per mm3 total bilirubin less than or equal to 1.5 mg per dL AST less than or equal to 100 U per L or 200 U per L in patients with liver metastases ALT less than or equal to 100 U per L or 200 U per L in patients with liver metastases serum creatinine less than or equal to 1.5 mg per dL urine protein 1 plus or less by dipstick test or urine protein to creatinine ratio less than or equal to 2.0. 12. Written informed consent for participation in the study has been obtained from the patient.
Exclusion criteria
Exclusion criteria: 1. The patient has active multiple primary malignancies defined as synchronous multiple cancers metachronous multiple cancers with a disease free interval of less than 5 years or multicentric cancers. The following malignancies are not considered active multiple primary malignancies even if the disease free interval is less than 5 years because they are associated with an approximately 95 percent or greater 5 year relative survival rate and have been adequately treated. These include gastric cancer adenocarcinoma common type Stage 0 to I colon cancer adenocarcinoma Stage 0 to I rectal cancer adenocarcinoma Stage 0 to I esophageal cancer squamous cell carcinoma adenosquamous carcinoma or basaloid carcinoma Stage 0 breast cancer including non invasive ductal carcinoma or non invasive lobular carcinoma Stage 0 and invasive ductal carcinoma invasive lobular carcinoma or Paget disease Stage 0 to IIA endometrial cancer endometrioid adenocarcinoma or mucinous adenocarcinoma Stage I prostate cancer adenocarcinoma Stage I to II cervical cancer squamous cell carcinoma Stage 0 thyroid cancer papillary carcinoma or follicular carcinoma Stage I to III renal cell carcinoma clear cell carcinoma or chromophobe carcinoma Stage I and other lesions equivalent to intraepithelial or mucosal carcinoma such as superficial oropharyngeal or hypopharyngeal cancer. Cancer staging should be based in principle on the UICC TNM Classification 7th Edition or equivalent Japanese cancer classification systems. 2. The patient has an active infection requiring systemic treatment. 3. The patient is pregnant potentially pregnant within 28 days postpartum or breastfeeding or is a male patient wishing to conceive with a partner. 4. The patient has a psychiatric disorder or psychiatric symptoms that interfere with daily life making participation in the study difficult to judge. 5. The patient is receiving continuous systemic treatment with corticosteroids or other immunosuppressive agents administered orally or intravenously. 6. The patient has poorly controlled hypertension. 7. The patient has ischemic heart disease with onset or worsening of symptoms within the past 3 weeks. 8. The patient has poorly controlled valvular heart disease dilated cardiomyopathy or hypertrophic cardiomyopathy. 9. The patient has active or persistent bleeding. 10. The patient has brain metastases or leptomeningeal or malignant meningeal metastases. In patients with central nervous system symptoms absence of metastases must be confirmed by contrast enhanced CT or MRI. 11. The patient has ascites pleural effusion or pericardial effusion requiring drainage within the past 4 weeks. 12. The patient has current or prior interstitial lung disease. 13. The patient shows obvious interstitial abnormalities active radiation pneumonitis or inflammatory changes due to infectious pneumonia on chest imaging. 14. The patient has unstable thromboembolic disease. This excludes catheter related thrombosis not requiring intervention or adequately treated cases and lower extremity thrombosis that is stable under treatment with direct oral anticoagulants or other anticoagulant therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Dose-Limiting Toxicities | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate, Duration of Response, Progression-Free Survival, Overall Survival, Incidence of Adverse Events | — |
Contacts
Public ContactToshiharu Hirose
National Cancer Center Hospital (Japan)
Outcome results
None listed