A Phase Ib/II study of Fruquintinib and FTD/TPI in Patients with Colorectal Cancer and Gastric Cancer

JRCT ID: jRCT2031240630

Registered date:24/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Unresectable Metastatic Colorectal Cancer and Gastric Cancer
• Date of first enrollment: 26/02/2025
• Target sample size: 66
• Study type: Interventional

Intervention(s)

[Phase Ib]
The RD of Fruquintinib will be determined based on the presence or absence of dose limiting toxicity (DLT) following the dosage and administration of 1 course. DLT will be evaluated in course 1 and if until the start of course 2.
- Level 0
Fruquintinib (5mg/body, once daily, Day1-21, orally, q4w)
FTD/TPI (35mg/m2, twice daily, Day1-5, 8-12, orally, q4w)
- Level -1
Fruquintinib (4mg/body, once daily, Day1-21, orally, q4w)
FTD/TPI (35mg/m2, twice daily, Day1-5, 8-12, orally, q4w)
[Phase II]
The RD determined on the results of tPhase Ib part will be administered.

Outcome(s)

Primary Outcome

[Phase Ib] Incidence of DLT
[Phase II] Disease control rate (DCR) assessed by the investigator or subinvestigator

Secondary Outcome

- Disease control rate (DCR) (evaluated in phase Ib)
- Objective response rate (ORR)
- Progression-free survival (PFS)
- Duration of response (DoR)
- Overall survival (OS)
- Adverse event rate

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Histologically confirmed as colorectal adenocarcinoma or gastric adenocarcinoma.
2. The patient was 18 years of age or older on the date of enrollment.
3. The patient had evaluable or measurable lesions as specified in the New Guidelines for Evaluation of Response to Treatment in Solid Tumors [Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1].
4. The patient had previously received at least 1 regimen of standard chemotherapy for mCRC or advanced gastric cancer. The patient was unresponsive to or intolerable to the chemotherapy.
a. Standard chemotherapy for mCRC must include all of the following agents:
i. Patients who are refractory or intolerant to at least one regimen of chemotherapy including fluoropyrimidines, oxaliplatin, and irinotecan (with or without anti-VEGF antibody)
ii. Patients with wild-type RAS, at least one anti-EGFR monoclonal antibody (cetuximab or panitumumab, etc.)
iii. Patients with microsatellite instability-high (MSI-H) or mismatch repair (MMR) deficient, at least one immune checkpoint inhibitor (nivolumab, pembrolizumab, and ipilimumab, etc.)
iv. Patients with BRAF V600E mutation-positive, who are refractory or intolerant to at least one regimen of chemotherapy including encorafenib, a BRAF inhibitor
v. Patients with HER2-positive, at least one anti-HER2 antibody (trastuzumab or pertuzumab, etc.)
b. Standard chemotherapy for unresectable advanced gastric cancer must include all of the following drugs.
i. Patients who are refractory or intolerant to at least one regimen of chemotherapy including fluoropyrimidines, platinum agents, and taxanes (with or without ramucirumab, etc.)
ii. Patients with HER2-positive, at least one anti-HER2 antibody (trastuzumab or trastuzumab deruxtecan, etc.)
iii. Patients with MSI-H or MMR deficient, at least one immune checkpoint inhibitor (nivolumab, pembrolizumab, etc.)
5. ECOG performance status (PS) of 0 or 1.
6. Has met all of the following criteria on laboratory test within 14 days before enrollment (Inspection on the same day of the week two weeks before the date of registration is permitted.)
i. Neutrophil count >= 1,500/mm3
ii. Hemoglobin >= 8.0 g/dL (excluding measurements within 7 days after transfusion of packed red blood cells or whole blood
iii. Platelet count >= 100,000/mm3 (excluding measurements within 7 days after platelet transfusion
iv. Total bilirubin <= 1.5 mg/dL
v. AST (GOT) <= 100 IU/L (<= 200 U/L if liver metastases are present)
vi. ALT (GPT) <= 100 IU/L (<= 200 U/L if liver metastases are present)
vii. Serum creatinine <= 1.5 mg/dL
viii. Urine protein < 2.0 g/24h or proteinuria <= 2+, or urine protein/creatinine ratio < 2
ix. PT-INT <= 1.5 or aPTT <= 60 sec
7. Grade 1 or no residual side effects from previous treatment (Alopecia is excluded.).
Participants with any of the following grade2 chronic toxicities that are determined by the investigators to be related to prior treatment may be enrolled (not worse than grade 2 for at least 3 months prior to enrollment, defined as manageable with standard therapy).
- Chemotherapy-induced neuropathy
- Fatigue
8. No blood transfusion within 7 days before enrollment. (Transfusions on the same day of the week before enrollment are acceptable.)
9. Women of childbearing potential have a negative pregnancy test within 7 days before enrollment. Both men and women agree to use appropriate contraception during the study and up to specified period (90 days for men and 180 days for women) after discontinuation of study drug.
10. Oral administration is possible.
11. Written consent to participate in the study was obtained from the patients.

Exclude criteria

1. Simultaneously active malignant disease (Synchronous double cancers and metachronous double cancers with a disease-free interval of 2 years or less. However, carcinomas in situ and lesions corresponding to carcinoma in situ that are considered curable with local treatment are not included in active double cancers.)
2. Metastasis to the central nervous system has been confirmed. (Confirmation by brain CT scan or MRI is mandatory at screening only when central nervous system metastases are clinically suspected.)
3. Uncontrolled hypertension
4. Patients with serious complications (Intestinal paralysis, intestinal obstruction, pulmonary fibrosis, difficult-to-control diabetes mellitus, renal failure, hepatic failure, psychiatric disorder, ulcer requiring blood transfusion, etc.) requiring hospitalization at the time of enrollement.
5. Those who have had a stroke or transient ischemic attack within 6 months prior to enrollment.
6. Patients with clinically significant cardiovascular disease (including but not limited to acute myocardial infarction or coronary artery bypass surgery), unstable angina, or New York Heart Association class III or IV congestive heart failure within 6 months prior to enrollment.
7. Patients with the following infections:
- HBs antigen positive
- HBs antibody or HBc antibody positive and HBV-DNA positive
- HCV antibody positive
- HIV positive
- Other treatable active infections
8. Patients received antineoplastic therapy such as chemotherapy, radiotherapy, or immunotherapy or any investigational treatment within 2 weeks before study drug enrollment.
9. Patients have received Fruquintinib and/or FTD/TPI (Participants in placebo-controlled trials involving Fruquintinib and/or FTD/TPI could not be enrolled.).
10. The patient is pregnant or breastfeeding.
11. The patient is unwilling or unable to comply with the protocol.
12. The investigator or subinvestigator judged the patient to be unsuitable for investigator-initiated clinical trials.

Related Information

• Primary Sponsor: Bando Hideaki