RAS/BRAFV600E Mutation-Positive Refractory Advanced Colorectal Cancer
Conditions
Interventions
RAS mutation cohort:HL085 + Fruquintinib + HCQ
BRAFV600E mutation cohort:HL085 + Fruquintinib + HCQ
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Signed informed consent; ECOG 0-2, aged between 18 and 75 years, regardless of gender; Histologically or cytologically confirmed recurrent or metastatic adenocarcinoma of the colon or rectum; Tumor biopsy and genetic testing confirm RAS mutation (NRAS or KRAS Q61 mutation), or BRAF V600E mutation-positive; For patients with RAS mutations, prior standard therapy including oxaliplatin, irinotecan, and fluorouracil; For BRAF V600E Patients with mutations, previously treated with drugs containing oxaliplatin and fluorouracil; At least one measurable lesion as assessed according to RECIST v1.1; Estimated survival > 3 months; Able to take medication orally; Laboratory tests within 7 days prior to randomization showed that the patient had good bone marrow function, liver and kidney function; (1) Routine blood count: hemoglobin >=80 g/L (no blood transfusion within 14 days), absolute neutrophil count>=1.5×10^9/L, platelet count>=100×10^9/L; (2) Electrolytes: there is no uncorrected electrolyte imbalance; (3) Liver function: total bilirubin 60 mL/min; (5) Cardiac function: left ventricular ejection fraction (LVEF) >=55%, ECG QTcF=2, 24-hour quantitative urine protein examination should be carried out, such as quantitative examination=1 g/24 h can not be enrolled, such as urine protein >=2 Cannot be enrolled without quantitative examination; Women of childbearing potential must have a negative pregnancy test (serum or urine) result within 14 days prior to enrollment and voluntarily use an appropriate method of contraception during the observation period and within 3 months after the last dose of study drug; For males, should be surgically sterile or agree to use an appropriate method of contraception during the observation period and for 3 months after the last administration of study drug; Able to cooperate in the observation of adverse events and efficacy, and voluntarily sign a written informed consent form.
Exclusion criteria
Exclusion criteria: Those who are allergic to the drugs in this regimen, and those who are known to have contraindications that affect the use of therapeutic drugs that affect the investigator's choice of treatment (in accordance with the latest drug instructions); Patients with a history of other malignancies within the past 5 years, with the exception of patients with completely cured basal cell carcinoma of the skin or squamous cell carcinoma of the skin and carcinoma in situ of the cervix and/or patients with any malignancy whose cancer has been cured without disease or have been disease-free for at least 5 consecutive years; Patients with no other evaluable lesions other than cancerous seous effusions (pleural effusion/ascites/pericardial effusions) or bone metastases (including identifiable soft tissue lesions); Subjects with symptomatic or untreated brain metastases, meningeal metastases, or spinal cord compression, with the following exceptions: subjects with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms due to brain metastases, no need for corticosteroids or antiepileptic medications, and stable lesions confirmed by imaging >=4 weeks); Patients treated with stereotactic brain radiotherapy or surgery without brain progression over a period of > = 3 months may be enrolled; Receipt of any investigational therapy, including chemoradiotherapy, biologic therapy, and immunotherapy, within 4 weeks prior to treatment (except for subjects who have had palliative radiotherapy with bone metastases within 2 weeks, but have received bone marrow irradiation within 2 weeks with an area >= 30% treatment is not allowed to enroll); Before the administration of the study drug, all relevant anti-tumor treatment toxicities (except alopecia, skin pigmentation, grade 2 chemotherapy-related peripheral neurotoxicity, etc.) did not recover to the level of =3 grade (CTC-AE), such as imaging during the screening period showing that the tumor surrounds important blood vessels or there is obvious necrosis and cavitation, and the investigator believes that participation in the study may cause bleeding risk; Has a history of active gastric/duodenal ulcer, ulcerative colitis, active bleeding from the digestive tract, perforation, or fistula; or any condition judged to be likely to cause bleeding or perforation in the digestive tract; Thrombotic events, including deep vein thrombosis (DVT), pulmonary embolism (PE), or arterial embolism, within 6 months prior to the study; History of stroke or transient ischemia within 12 months prior to the study; Patients with G6PD deficiency, severe psoriasis, porphyria, macular degeneration; Patients with rare genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption; Patients who are allergic to 4-aminoquinolines; Retinal diseases in the past or at screening, such as: retinal vein occlusion (RVO), retinal artery occlusion, retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal telangiectasia (Costs d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival;Disease control rate;Overall survival;Duration of Response;Safety; | — |
Countries
China
Contacts
Public ContactXicheng Wang
Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College
Outcome results
None listed