The National Cancer Center Hospital, Japan: Cutting-edge Drug Discovery in the Modality-Driven Era

How the MASTER KEY Project Solves Challenges in Rare Cancer Clinical Trials

According to the National Cancer Center, 'rare cancers' are defined as 'malignant tumors with an incidence rate of less than 6 cases per 100,000 individuals'. Since the number of patients with these rare cancers is extremely small, it can be extremely difficult to conduct large-scale clinical trials and collect medical data. Although the Japanese government provides strong support from a regulatory perspective, medical and drug development companies are not necessarily enthusiastic about treatments for rare cancers due, in part, to their low cost-effectiveness.

Against this backdrop, the National Cancer Center launched the MASTER KEY (MK) project in 2017, aiming to establish a rare cancer registry. This registry would then promote the efficient development of rare cancer drugs through collaboration between industry, academia, and patients.

The initial research phase of this project accumulated a large database of rare cancer patients and the characteristics of rare cancers – including biomarkers. The next phase involved clinical trials, with registered patients receiving the most appropriate clinical sub-trial according to their own biomarker results. More than 3,000 rare cancer patients have already been registered as part of the MK project, and 27 clinical trials are underway.

Figure 1: Overall view of the MASTER KEY project

The number of facilities participating in the project has already expanded to seven across Japan, but these are all concentrated in urban areas. To date, this has made it difficult for patients living in rural areas to participate in the clinical trials. That is why the MK project's recent focus has been on the introduction of decentralized clinical trials (DCTs).

We have consulted with Dr. Nakamura to explain the background behind the introduction of DCTs.

"Recently, cancer gene panel tests have been covered by patients' insurance policies. However, even if patients undergo these panel tests, very few will be given the therapeutic drugs for their rare cancers – only 8.1%. The main reason for this low percentage is due to the limited opportunities that patients in rural areas have for participation in clinical trials. For example, the National Cancer Center Hospital conducts 525 oncology trials, but that number drops to single digits at regional university hospitals. However, that doesn't mean that we should force patients to travel long distances to participate." – Dr. Nakamura

What is the 'Full-Remote DCT' Scheme?

This new decentralized clinical trial scheme introduced by the MK project is called 'full-remote DCT'. Dr. Nakamura summarised for us how this scheme works.

"Suppose there is a patient who lives in a rural area and wishes to take a clinical trial. Under the full-remote DCT scheme, the patient can undergo the tests required for the clinical trial at a partner facility near his or her home. The test results are shared with the National Cancer Center Hospital via the cloud, and the patient is then connected to the hospital for online medical care to complete the trial.

"The online clinic will be conducted in the presence of the attending physician at the partner facility. The partner facility also serves as the patient's family doctor, providing a great sense of security for the patient. The partner site is provided with a touchpad with the online clinical trial system installed, and patients sign their names digitally on the touchpad after receiving an explanation of the trial via videoconference. The study drug is delivered directly from the hospital to the patient's home." – Dr. Nakamura

Figure 2: Full remote DCT scheme (Japan)

The MK project is expanding the number of partner facilities signed up to the program so that patients in a wider area can receive clinical trials, but there are two technical points to be considered for the nationwide expansion of DCTs in the future.

"First, we need to ensure smooth data sharing between facilities. Medical information is extremely sensitive, and it is true that there are regulatory hurdles when it comes to sharing it on the cloud. Each hospital has a different approach to security, so we must clear that first. In this sense, DDC (Direct Data Capture, direct collection of electronically recorded data), which is being used in the medical and pharmaceutical fields, must be promoted in parallel.

"Another is the maturation of DCT platforms. Currently, each vendor has each elemental technology of DCT in pieces. There is no integrated platform. If a truly unified platform can be created, it will be a catalyst for the rapid progress of DCT." – Dr. Nakamura

How We Can Expand the Use of Cross-Border DCTs

Furthermore, Dr. Nakamura would like to expand this scheme beyond its domestic use in Japan and across national borders. He is already working on concrete steps toward this goal of 'cross-border DCTs'.

"It is clear that Japan, with its declining population, has a limit to how much it can do on its own in terms of clinical trials and clinical studies. It is clear from the development of the vaccine for the coronavirus infection that Japan needs the help of other countries as well. With such a sense of crisis, the Japanese government has been promoting the creation of clinical trial networks across Asia in the fields of infectious diseases and oncology. Against this background, we have launched the Asia Clinical Trials Network for CancerS (ATLAS) with the support of the government and AMED. ATLAS was launched with the support of the government and AMED." – Dr. Nakamura

There have been some concerns about the joint development of drugs in Asia, which ATLAS will be responsible for. These include concerns about safety if each country has little experience in clinical trials, as well as the potential for increased costs when compared to domestic trials. However, the introduction of cross-border DCTs will eliminate these obstacles.

"I came up with this idea on April Fool's Day, April 1, 2022. People say that new ideas are a combination of existing ideas. At that time, I happened to be on a mission to create an online clinical trial and build a clinical trial network in Asia. I thought it would be interesting to cross these ideas together. The scheme for online clinical trials in Japan can be deployed directly across Asia, so new system development is minimal." – Dr. Nakamura

Figure 3: Full-remote DCT scheme (Cross-border)

However, the implementation of cross-border DCTs was not without challenges. The biggest hurdle was not the system but the regulatory aspect. Specifically, the issue of medical licenses.

"For example, discussions with the Thai Ministry of Health revealed that a Japanese doctor who does not have a medical license to practice online in Thailand would not be able to provide online medical care to a patient living in Thailand. If that remained the case, cross-border DCTs could not be realized." – Dr. Nakamura

Fortunately, a solution was soon found. There was a system in place that allowed doctors with special skills to be issued a special license to practice medicine in Thailand.

"With the cooperation of the government and the Ministry of Health, I went to the Thai Ministry of Health, and after repeated negotiations, we concluded a memorandum of understanding to promote online clinical trials. Recently, we obtained an agreement to issue a license. Now that the partnership with Thailand has been realized, other countries that had previously shied away from the scheme are showing interest.

"The biggest hurdle has been removed, so all that remains is to do it. If this scheme is realized, it will be a win-win-win-win for everyone, including patients, medical institutions, and pharmaceutical companies, so we are determined to make it happen." – Dr. Nakamura

As a vendor contributing to the future of healthcare and pharmaceuticals

The utilization of advanced technology in various fields has been accelerating, as introduced so far. The backbone supporting this advancement is undoubtedly the presence of development vendors. From the vendor's perspective, Mr. Shikou Sekine from the Pharmaceutical and Chemical Business Division in NTT DATA, summarized as follows:
"As reported in June 2023 by Nikkei Japanese newspaper, Japan ranks at the forefront globally when calculating the competitiveness of patents for innovative cancer treatments. While Europe and the United States have dominated global cancer research in the past, we could expect that pharmaceutical and anticancer drug development in Asia would become a hot topic in the future just as the growth of Asian countries in the world economy. If these initiatives continue to expand, Clinical Trials for patients would become as more accessible options. We're almost there to see such a world where better healthcare would be delivered to ass many patients as possible. NTTDATA, as an IT vendor, aims to contribute in various ways to build platforms that connect healthcare, pharmaceuticals, and patients.

Profile of Kenichi Nakamura
Director of the Department of International Clinical Development at National Cancer Center Hospital, Japan

Dr. Nakamura is the director of the Department of International Clinical Development and the project leader of the ATLAS project. He also serves as the director of the Japan Clinical Oncology Group (JCOG) Operatins Office. He has a lot of experience to manage various types of clinical trials ranging from early-phase investigator-initiated registration directed trials to large-scale pragmatic trials. As a specialist of clinical trial operation and regulation, he engages in several international projects such as the revision of ICH-GCP, collaborative studies with EORTC and IRCI, research ethics project on CRIGH.

Profile of Shikou Sekine
Senior Manager of Pharmaceutical & Chemical Division, Industry Business Sector at NTT DATA Corporation

After working in a major pharmaceutical company, Sekine joined NTT DATA in 2003. He has an experience in leading and directing a wide range of pharmaceutical process transformations, including new business development for the pharmaceutical industry, clinical development, distribution, sales, and PMS (Post-Marketing Surveillance) as Project Manager and Director.