Status: New
| Name & address of the Laboratory/Organization | Tata Memorial Centre | |
| Website address | https://tmc.gov.in | |
| Affiliated to which Department/Ministry | Department Of Atomic Energy (DAE) | |
| CSR Registration Number | CSR00001287 | |
| Registration under 12A | INS/12128 Provisional approval no.- AAATT3620RE20214 | |
| Registration under 80G | DIT(E)/ITO(Tech)/80G/2010-11 Provisional approval no.- AAATT3620RF20241 | |
| Name of the CSR Nodal | Dr Heena Shaikh | |
| Contact information of CSR Nodal | +91-22 -68735000 Extn: 5483, hshaikh@actrec.gov.in | |
| Principal Investigator | Dr Vanita Noronha, hshaikh@actrec.gov.in | |
| Co- Principal Investigator (Co-PI) | ||
| Objective on the basis of need | To develop cost-effective treatment for patients with advanced lung cancer that carries the ALK gene alteration |
| Executive summary of the proposed project (In 250 words) | Advanced lung cancer with a genomic change (ALK-positive) can be effectively treated with targeted drugs called ALK inhibitors. Newer ALK inhibitors like lorlatinib are more effective than earlier ALK inhibitors like crizotinib. Lorlatinib, however, causes severe side effects in 72% patients. The approved dose of lorlatinib (100 mg tablets daily) is probably higher than the dose required to shrink the tumor. In the earliest dose-finding study, all dose levels of lorlatinib, even 25 mg daily led to tumour shrinkage. The investigators also found no connection between lorlatinib dose and effectiveness, but there was a clear relationship between lorlatinib dose and side effects. This means that a lower dose of lorlatinib would lower the side effects and would likely remain effective. Lorlatinib is very expensive and unaffordable for almost all patients. Crizotinib is also expensive, and only approximately 40% of our patients can afford to buy crizotinib. We therefore propose a randomized clinical trial in patients who have not received previous ALK-targeted therapies. Participants will be randomly assigned to receive either reduced-dose lorlatinib (25 mg tablets daily) or crizotinib (250 mg tablets twice a day). Treatment will continue until disease progression. If we are able to show that in patients who have not yet received any treatment with an ALK inhibitor, a much lower dose than the standard approved dose can effectively control the disease, and results in less toxicity, this would be of great value to patients and society. |
| Technology Readiness Level (If not a new project but an advancement of existing know how) | Testing for ALK rearrangement is done routinely at our institution by immunohistochemistry, fluorescence in situ hybridization, and next generation sequencing. Testing for ALK gene rearrangement has been a standard practice for patients with advanced lung cancer for many years. In terms of clinical trial expertise, our team at the Tata Memorial Centre has done multiple clinical trials over the past few decades and is skilled at all aspects of clinical trial implementation. Our institution has an independent ethics committee, data safety monitoring committee, biostatisticians, and access to clinical trial data entry software like RedCap. |
| Outomes or Deliverables | The study will monitor patients for disease progression, response to treatment, and side effects. The study aims to evaluate if a lower dose of lorlatinib (25 mg daily) can be more effective than standarddose crizotinib in treating advanced ALK-positive lung cancer. We hope that this will show that disease control is better with this low dose lorlatinib with increase in life while maintaining quality of life. The hope is that reduced-dose lorlatinib will be effective, safer, and more affordable for patients in need. |
| Project aligned with which most relevant UN SDGs | Goal 10 - Reduced Inequalities |
| Duration (In years) | 3 years |
| Expected Impact | Most patients in India cannot afford treatments for ALK-positive advanced lung cancer. One month of lorlatinib costs Rs 2,60,000. Thus, very few patients can afford lorlatinib. At Tata Memorial Hospital, the cost of lorlatinib 100 mg orally daily (with the patient assistant program) is Rs 15 lakhs for the first year, Rs 10 lakhs for the second year, Rs. 10 lakhs for the third year. The cost of lorlatinib without the patient assistance program is double what has been provided above. The median income in India is Rs 27,300 per month, or Rs 3,27,600 per year . Thus, even if the entire income of the family were to be utilized only for the purchase of medicines, lorlatinib would not be affordable for the average Indian. In an audit of the standard treatment taken by the patients at our institution, less than 5% of our ALK positive patients are able to take lorlatinib on their own. Once we prove this low dose of lorlatinib is useful than this can be used by majority of the ALK positive non-small cell lung cancer patients in this country. Cost of lorlatinib at low dose will be one third of the cost today. The cost will be within the limits of national and many state insurance program by the government of India or state government schemes, ensuring that almost everyone gets access to this treatment. Considering the drugs used, this has potential to get implemented with limited resources. This has potential of significantly increasing life of these patients. If these treatments are not provided, then average life of these patients is around 10-12 months. With these treatments, we expect that almost 65% patients will have disease control at 5 years and almost 80% patients may remain alive at 5 years. These patients are usually adults, and they support their family financially and logistically, they are usually employed contributing to society and economy. Improvement and increase in life of these patients also impacts the family of the person and contributes to the economy of the country. |
| Implementation model (self- implemented/ outsourced partnership) | Self-implemented. We will conduct the study at Tata Memorial Centre. |
| Total Budget (Recurring +Non-Recurring Expenses) | Rs 4,58,08,288/- |