A Prospective, Single-arm, Single-center, Phase II Clinical Study of Ivosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer: Efficacy and Safety Assessment
Overview
- Phase
- Phase 2
- Intervention
- Ivosidenib (AK112)
- Conditions
- CRC
- Sponsor
- Fudan University
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- PFS
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a prospective, single-arm, single-center Phase II clinical study. In this study, participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. The treatment regimen is as follows: participants will first receive Ivosidenib in combination with CapeOX chemotherapy during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If extensive primary and metastatic lesions cannot be treated with radiotherapy initially, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered.
Assessments will be conducted every 2 treatment cycles after treatment initiation, with multidisciplinary team (MDT) discussions to determine if No Evidence of Disease (NED) is achieved. Patients achieving NED may undergo surgery or local treatment, while those with stable or partial responses will continue combination therapy. Patients with disease progression will discontinue study treatment. Patients ineligible for surgical treatment will continue combination therapy until disease progression or until they exit the study for surgical treatment.
During the study period, participants will undergo safety monitoring. The safety follow-up period is defined as 90 days after the last dose of Ivosidenib. Safety data will be collected from the time of informed consent signing until the end of the safety follow-up period or initiation of new anti-tumor treatment (whichever occurs first).
Detailed Description
This is a prospective, single-arm, single-center Phase II clinical study. In this study, participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. The treatment regimen is as follows: participants will first receive Ivosidenib in combination with CapeOX chemotherapy during the first cycle, followed by radiotherapy starting 2 weeks after medication. Depending on the dose limits of normal tissue radiation, Stereotactic Ablative Radiotherapy (SABR), large fraction radiotherapy, or high-dose combined with low-dose radiotherapy will be administered to primary and metastatic lesions. One week after completing radiotherapy, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment. If extensive primary and metastatic lesions cannot be treated with radiotherapy initially, participants will continue to receive Ivosidenib in combination with CapeOX systemic treatment until the lesions shrink, at which point radiotherapy may be considered. Assessments will be conducted every 2 treatment cycles after treatment initiation, with multidisciplinary team (MDT) discussions to determine if No Evidence of Disease (NED) is achieved. Patients achieving NED may undergo surgery or local treatment, while those with stable or partial responses will continue combination therapy. Patients with disease progression will discontinue study treatment. Patients ineligible for surgical treatment will continue combination therapy until disease progression or until they exit the study for surgical treatment. During the study period, participants will undergo safety monitoring. The safety follow-up period is defined as 90 days after the last dose of Ivosidenib. Safety data will be collected from the time of informed consent signing until the end of the safety follow-up period or initiation of new anti-tumor treatment (whichever occurs first).
Investigators
LI XIN-XIANG
professor
Fudan University
Eligibility Criteria
Inclusion Criteria
- •ECOG performance status of 0-
- •Initial diagnosis confirmed by colonoscopy and pathology as colorectal adenocarcinoma.
- •Imaging confirmation of multiple measurable metastases, deemed unresectable initially after MDT discussion.
- •No prior treatment or more than 1 year since completion of initial untreated/post-operative adjuvant chemotherapy, and no previous anti-tumor therapy thereafter.
- •With good organ function, without contraindications for surgery or chemotherapy.
- •Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, and international normalized ratio (INR) ≤ 1.5 × ULN (if not receiving anticoagulant therapy).
- •Urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein quantitative test must show ≤ 1g protein.
- •Left ventricular ejection fraction (LVEF) ≥ 55%. 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) \< 470 msec.
- •Expected survival \> 6 months.
- •Clear status of KRAS, NRAS, BRAF, and HER2 genes.
Exclusion Criteria
- •Age \<18 years or \>75 years.
- •History of any other malignancy within 5 years, except adequately treated cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma that has been effectively controlled.
- •Malignant pleural or peritoneal effusion.
- •Severe internal medical complications preventing chemotherapy or surgery.
- •Clinical or radiological evidence of spinal cord compression, or tumor within 3 mm of the spinal cord on MRI.
- •Imaging-confirmed brain, ovarian, or peritoneal metastases.
- •Patients deemed suitable for aggressive systemic treatment to achieve conversion after MDT discussion.
- •Pathologically diagnosed signet ring cell carcinoma.
- •Patients with microsatellite instability or mismatch repair protein deficiencies.
- •Patients with intestinal obstruction, perforation, bleeding requiring emergency surgical resection.
Arms & Interventions
AK112 combined with CapeOX and radiotherapy
Participants will receive Ivosidenib in combination with CapeOX chemotherapy and radiotherapy. Participants will first receive Ivosidenib in combination with CapeOX during the first cycle, followed by radiotherapy starting 2 weeks after medication.
Intervention: Ivosidenib (AK112)
Outcomes
Primary Outcomes
PFS
Time Frame: The time from the start of treatment until disease progression (PD) or death from any cause，whichever came first, assessed up to 100 months
Progression-Free Survival (PFS)