A Phase II Single-Arm Trial to Evaluate the Efficacy of Low-Dose Nivolumab (40 mg) as Neoadjuvant Treatment in MSI-High Locally Advanced Rectal Cancer (LARgE CLOuD)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Primary objective: To evaluate the clinical complete response (cCR) rate of low-dose nivolumab (40 mg) as neoadjuvant therapy in MSI-H locally advanced rectal cancer.
研究概览
简要总结
The study is led by Dr. Vikas Ostwal and a team of doctors at Tata Memorial Hospital, Mumbai. This study will be conducted in Tata Memorial Centre, Mumbai.
This study is testing a cancer medicine called Nivolumab in patients with locally advanced rectal cancer. The goal is to see if a low dose (40 mg) of this medicine can help shrink the tumor before surgery, reducing the need for chemotherapy and radiation.
Most rectal cancer patients get chemotherapy and radiation before surgery, but this can have many side effects like bowel and bladder problems. Some rectal cancers, especially those with a specific genetic feature (MSI-High), may respond better to immunotherapy instead. This study is testing a lower dose of Nivolumab to make treatment more affordable, effective, and safer.
- 53 patients will receive low-dose Nivolumab (40 mg) through an IV every 2 weeks for 6 monthly
- After treatment, doctors will check if the cancer has completely disappeared (called clinical complete response or cCR).
- If the tumor is gone, patients will be closely monitored instead of having immediate surgery (a "watch-and-wait" approach).
- If the tumor is still present, patients will receive standard chemotherapy and surgery.
The main goals of the study are :
- To check how many patients achieve a complete response after Nivolumab treatment.
- To evaluate how long patients remain cancer-free (progression-free survival and overall survival).
- To monitor side effects and safety of the low-dose treatment.
- To assess patients’ quality of life during and after treatment.
Who can participate?
- Adults (18+ years) with MSI-High rectal cancer that has not been treated before.
- Patients in good overall health, with normal organ function.
- Women of childbearing age must use contraception during treatment.
Who cannot participate?
- Patients who already had treatment for rectal cancer.
- Patients with spreading (metastatic) cancer.
- Patients with severe medical conditions or active infections like Hepatitis or HIV.
- Pregnant or breastfeeding women.
What are the benefits of this study?
- If successful, patients may avoid surgery and chemotherapy while still being cancer-free.
- Low-dose treatment reduces costs and side effects, making it more accessible.
- This research can improve cancer care worldwide, especially in resource-limited countries.
How long will the study last?
The study will run for 4 years, with regular check-ups and follow-ups.
Are there any risks?
Nivolumab can cause immune-related side effects like skin rash, fatigue, diarrhea, or changes in hormone levels. These will be closely monitored during the study.
What will be provided to patients?
- Free Nivolumab treatment and necessary tests.
- Financial support for travel expenses.
- Patients must cover the cost of surgery if needed.
Conclusion
This study aims to prove that low-dose Nivolumab can effectively treat rectal cancer while reducing costs and side effects. If successful, it may change how rectal cancer is treated, offering a less aggressive but equally effective approach.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 85.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Subjects must have histologically confirmed MSI-H locally advanced rectal cancer 2.Male or female subjects aged more than or equal to 18 years.
- •3.Patients who have not received any treatment for rectal cancer.
- •4.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–
- •5.Subjects must have normal organ and marrow function.
- •6.Patients with HIV are potentially eligible, as long as they have a CD4 count more than 200, are on concurrent HAART (highly active antiretroviral therapy), and have no active AIDS-defining conditions.
- •7.Negative serum or urine pregnancy test at screening for women of childbearing potential.
- •8.Contraception.
- •9.Both men and women of all races and ethnic groups are eligible for this study.
- •10.Willing and able to comply with all study requirements, including treatment and regular follow-up assessments.
- •11.Ability to understand and willingness to sign a written informed consent document.
排除标准
- •1.Patients with metastases 2.Previously treated rectal cancer patients 3.Patients on other investigational agents 4.Chemotherapy within 3 weeks 5.Current use of immunosuppressants except low-dose steroids or specific short-term uses 6.Active autoimmune disease requiring immunosuppressants 7.Prior organ or stem cell transplant 8.Active infection needing systemic treatment 9.Active hepatitis B or C 10.Vaccination within 4 weeks before or during study (except inactivated vaccines) 11.Severe hypersensitivity to study drug or monoclonal antibodies 12.Significant cardiovascular disease (stroke, MI, heart failure, arrhythmia within 6 months) 13.Unresolved toxicity from prior therapy unless mild and not risky 14.Severe medical or psychiatric conditions or abnormal labs that increase study risk 15.Pregnant women excluded; effective contraception required 16.Breastfeeding not allowed during and for 1 month after treatment 17.No prior immunotherapy use.
结局指标
主要结局
Primary objective: To evaluate the clinical complete response (cCR) rate of low-dose nivolumab (40 mg) as neoadjuvant therapy in MSI-H locally advanced rectal cancer.
时间窗: every 2 months upto 3 years
cCR can be defined as no evidence of active disease as per rectal examination, sigmoidoscopy and radiological evaluation
时间窗: every 2 months upto 3 years
次要结局
- 1.Pathological complete response (pCR) rate in patients undergoing surgery.(2.Disease -free survival (PFS) in patients undergoing surgery..)
研究者
Dr Vikas Ostwal
Tata Memorial Hospital, Mumbai