Adjuvant chemotherapy for ctDNA positive patients- Randomized phase II study of comparing FOLFOX6 with FOLFOXIRI+Bevaxcizumab

JRCT ID: jRCT1071220087

Registered date:11/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: patients with positive ctDNA after curative resection for metastasis of colorectal cancer
• Date of first enrollment: 11/01/2023
• Target sample size: 74
• Study type: Interventional

Intervention(s)

At enrollment, each subject will be assigned to one of the following treatment groups
<mFOLFOXIRI +BV Group>
mFOLFOXIRI + BV therapy every 2 weeks for up to 8 cycles, followed by maintenance therapy for a total of up to 12 cycles.
<mFOLFOX6 Group>
mFOLFOX6 therapy every 2 weeks for up to12 cycles.

Outcome(s)

• Primary Outcome: the percentage of ctDNA negative conversion

Secondary Outcome

1) Time to ctDNA negative change
2) Recurrence free survival; RFS
3) Overall survival; OS
4) Adverse Events; AE

Key inclusion & exclusion criteria

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

Include criteria

1.The patient is diagnosed with colorectal cancer based on histological diagnosis of the primary lesion.
2. The patient is participated in COSMOS-CRC-03 study and has been performed surgical resection of the metastatic lesions.
3. The surgical resection is diagnosed as R0 pathologically.
4. ctDNA is positive at 28 days postoperatively, or positive during one-year follow-up period without recurrence at CT/MRI imaging.
5.Within 6 weeks after positeve ctDNA.
6. Patients will be eligible only if the history of chemotherapy or radiotherapy for the primary or distant metastases meets either of the conditions 1) or 2) below.
1) Prior chemotherapy for the primary or metastatic lesion was performed, and at least 28 days have passed since the final dose of chemotherapy at the time of enrollment.
2) Preoperative radiotherapy was administered for the primary or previous metastatic lesion.
7.If metastases to the liver or lungs are present, the patient has no history of cryotherapy or thermocoagulation therapy such as radiofrequency cauterization (including concomitant administration at the time of resection of metastases to the liver).
8.Being aged 18 years or above at the time of obtaining written consent.
9.ECOG Performance Status (PS) of 0 or 1. For patients aged 75 years or above, only a PS 0 is acceptable.
10.The patient has fulfilled all of the following test findings. (The latest test results within the period of 14 days before enrollment should be used. The day 1 week before the enrollment is acceptable)
1)Neutrophil count >= 1,500 / mm3
2)Platelet count >= 10 x 10^4 / mm3
3)GOT =<100 IU/L (If liver metastases are present, GOT =<150 IU/L)
4)GPT =< 100 IU/L (If liver metastases are present, GOT =<150 IU/L)
5)T. Bil =< 1.5 mg/dL
6)Cr =< 1.4 mg/dL
7) urinary protein =< 2+
11.wild-type (ie, *1/*1) or single heterozygous (ie, *1/*6 or *1/*28) UGT1A1 genotype.
12.Written consent to participate in the study has been provided by the patient himself/herself.

Exclude criteria

1)The patient has active multiple cancers .(synchronus multiple cancers, and metachronus multiple cancers with a disease-free period of 5 years or less. However, patients with intraepithelial or intramucosal cancer in any organ that is determined to have been cured with localized therapy can be enrolled)
2)In the case of female patients, the patient is possibly pregnant or is breastfeeding.
3)The patient has concurrent interstitial pneumonia, pulmonary fibrosis or severe emphysema.
4)The patient has concurrent psychiatric disease or psychiatric symptoms determined to make it difficult for the patient to participate in the clinical trial.
5)The patient is receiving continuous systemic steroid therapy (oral or intravenous).
6) The patients who have uncontrolled anticoagulant therapy.
7) The patient with non-healing wound (except for central venous port)
8) Surgery, biopsy with skin incision and suture procedure for traumatic injury within 28 days prior to the enrollment. (except for central venous port)
9) Requiring the continuous treatment of flucytosine, phenytoin, or warfarin potassium
10)The patient has concurrent diabetes mellitus that is being treated with continuous insulin administration or is poorly controlled.
11)Grade 2 or higher diarrhea or sensory neuropathy
12)The patient has concurrent poorly controlled hypertension.
13)The patient has a history of one or more of the following: serious heart disease, cardiac failure, myocardial infarction within the past 6 months or angina attacks within the past 6 months.
14)Patients whom the PI or investigators decided as inappropriate for the clinical trial.

Related Information

• Primary Sponsor: Oki Eiji
• Source(s) of Monetary Support: Guardant Health AMEA, Inc.