Combination therapy for advanced colorectal cancer after initial treatment failure

Fruquintinib Plus Camrelizumab and Capecitabine as Salvage Therapy After Progression on FOLFOXIRI-based First-line Treatment in Patients With Unresectable/Metastatic Colorectal Cancer: a Prospective Phase II Study

This study is testing a new combination of three drugs to see if it can help people with advanced colorectal cancer who didn't respond to their first treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: bevacizumab, cetuximab, camrelizumab, fruquintinib, chemotherapy, prednisone
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06148402 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness of a combination therapy involving fruquintinib, camrelizumab, and capecitabine as a salvage treatment for patients with unresectable or metastatic colorectal cancer who have progressed after first-line FOLFOXIRI treatment. The study is open-label and single-arm, meaning all participants will receive the same treatment without a control group. Eligible patients include those who have experienced disease progression or intolerable toxicity from previous treatments. The goal is to determine if this combination can provide a viable second-line treatment option for these patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable or metastatic colorectal cancer who have progressed on FOLFOXIRI or have experienced toxicity from previous treatments.

Not a fit: Patients with colorectal cancer that is resectable or those who have not progressed on first-line therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new salvage therapy option for patients with advanced colorectal cancer who have limited treatment choices.

How similar studies have performed: While this approach is novel in combining these specific therapies for this patient population, similar studies have shown promise in using targeted therapies for colorectal cancer.

Eligibility criteria

Inclusion Criteria:

1. Metastatic or locally advanced, unresectable colorectal cancer confirmed by histology or cytology
2. The occurrence of metastases after radical resection of colorectal cancer does not require additional histological or cytological confirmation unless more than 5 years since surgery for the primary tumor
3. Progression or toxicity intolerance of first-line treatment with or without targeted drugs (bevacizumab or cetuximab) with FOLFOXIRI regimen or the sequential administration of irinotecan, oxaliplatin, and fluorouracil within a year; if patients with BRAF mutations, who have been treated with BRAF inhibitor alone or in combination with MEK inhibitor also can be included.
4. Target lesion defined by the Response Evaluation Criteria in Solid Tumor (RECIST criteria)
5. Age ≥18 years old, performance status (ECOG) score ≤ 2
6. Estimated expectancy life at least 12 weeks
7. Adequate blood, liver and kidney function, as follows:

   1. Hemoglobin ≥8g/dl,
   2. neutrophil absolute count ≥1000/μL,
   3. platelets ≥ 75,000 /μL;
   4. Total bilirubin ≤1.5 x upper limit of normal (ULN),
   5. alkaline phosphatase, aspartate aminotransferase (AST (SGOT) and alanine aminotransferase (ALT (SGPT)) ≤2.5 x ULN (if liver metastasis is present, ≤5 x ULN),
   6. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance \>50mL/min (calculated according to Cockcroft Gault formula),
   7. urinary protein excretion (if protein \>30 mg/dL or 2+, 24-hour urinary protein quantity must ≤1g)
8. International Normalized Ratio (INR) or activated partial thromboplastin time (APTT) \<1.5 x ULN (thromboembolic event must be ruled out if D-dimer is abnormal)
9. Negative pregnancy test within 7 days before enrollment; Pregnancy tests can only be omitted in women who do not have any reproductive potential (e.g., postmenopausal women who had amenorrhea ≥2 years or prior hysterectomy or bilateral oophorectomy). Fertile wo-men and men must consent to the use of appropriate contraception at the time of enrollment and during study participation. If a woman becomes pregnant or suspects that she is pregnant while participating in this study, she must notify her physician immediately; Breastfeeding women must be excluded
10. Consent to provide blood samples for specific relevant analyses
11. Have the ability to understand and sign the written informed consent

Exclusion Criteria:

1. Received antitumor chemotherapy or biotherapy within 28 days prior to the first use of the investigational drug. The exception is a single dose of radiotherapy up to 8Gy for pain relief of non-target lesion during the first 14 days of enrollment
2. Untreated or symptomatic brain metastases
3. The exclusion criteria of fruquintinib are as follows:

   1. History of heart disease: Congestive heart failure (CHF) grade II or higher, according to the New York Heart Association (NYHA); Active coronary artery disease and myocardial infarction within 6 months prior to study initiation; New angina or unstable angina (occurrence at rest) that have not been evaluated within 3 months; arrhythmias that require antiarrhythmic therapy; except in participants who have been treated and who the investigator believes have stable/controlled disease;
   2. Uncontrolled hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg) and a history of hypertensive crisis or hypertensive encephalopathy;
   3. History of arterial thrombosis or embolism events (within 6 months)
   4. Critical vascular diseases (such as aortic aneurysm, aortic dissection, symptomatic peripheral vascular disease)
   5. People with bleeding tendency or coagulation disorder
   6. Had major surgery (including open biopsy, severe trauma, etc.) within 14 days prior to study enrollment, or expected to require major surgery during the study period, and had minor surgery (excluding Implantable Venous Access Port or peripherally inserted central venous catheter) within 7 days prior to study enrollment
   7. Abdominal fistula, gastrointestinal perforation, peptic ulcer or abdominal abscess in the past 6 months
   8. Severe, non-healing wounds, ulcers or fractures
   9. History of posterior reversible encephalopathy syndrome
   10. previous treatment with fruquintinib;
4. Inability to swallow tablets, malabsorption syndrome or any condition affecting gastrointestinal absorption; Patients with incomplete obstruction/obstruction syndrome/intestinal obstruction signs/symptoms at initial diagnosis may be admitted to the study if they have received definitive treatment (such as surgical) to resolve symptoms;
5. Active autoimmune disease or history of autoimmune disease with possible recurrence (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism \[controllable only by hormone replacement therapy can be included\]); Participants with non-systemic skin diseases such as vitiligo, psoriasis, and alopecia, type 1 diabetes controlled with insulin, or asthma in complete remission in childhood without any intervention as adults can be enrolled; Patients with asthma requiring medical intervention with bronchodilators are excluded;
6. Immunosuppressive or systemic hormone therapy for immunosuppressive purposes (dose \>10mg/ day prednisone or other therapeutic hormone) within 14 days prior to initiation of study therapy
7. Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia; Oral or intravenous administration of therapeutic antibiotics within 2 weeks prior to initiation of study treatment (patients receiving prophylactic antibiotics, for example, to prevent urinary tract infections or exacerbation of chronic obstructive pulmonary disease are eligible for study participation)
8. Patients with congenital or acquired immune deficiency (such as HIV infection)
9. Have received live attenuated vaccines within 28 days prior to initiation of study treatment, or are expected to require such vaccines during camrelizumab treatment or within 60 days after the last administration of camrelizumab
10. According to the investigator's judgment, the patient has other factors that may affect the study results or lead to the forced termination of the study, such as alcoholism, drug abuse, other serious diseases，including mental illness，requiring combined treatment, serious laboratory abnormalities, and family or social factors which will affect the safety of the patient

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Qiong Yang, doctor — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Qiong Yang, Doctor

Conditions Unresectable/Metastatic Colorectal Cancer; Fruquintinib; Camrelizumab; Capecitabine; mCRC; salvage therapy