How Is the Big Ten CRC Reshaping Early-Phase Breast Cancer Trials?

As the number of novel agents for patients with breast cancer continues to grow, investigators are reconsidering when, how, and for whom phase 1 trials are designed and opened.

CancerNetwork® spoke with Oana Danciu, MD, associate director of clinical research at the University of Illinois Cancer Center, professor in the Division of Hematology and Oncology at the University of Illinois College of Medicine Chicago, and steering committee chair of the Big Ten Cancer Research Consortium (Big Ten CRC), about the evolving landscape of early-phase breast cancer research.

She began by outlining the consortium’s strengths in launching investigator-initiated trials, including cross-institutional mentorship and centralized review processes. Danciu then discussed how the profile of patients entering phase 1 breast cancer trials has shifted and how the FDA’s Project Optimus has influenced dose-finding design. She also described the operational barriers to opening early-phase trials and the University of Illinois Cancer Center’s efforts to expand access for patients who are underserved. She concluded by highlighting the drug classes she is most excited to see advance into later-stage testing.

CancerNetwork: As a steering committee chair of the Big Ten CRC, what do you see as the consortium’s biggest strengths in getting investigator-initiated trials off the ground?

Danciu: I really love working with the Big Ten CRC. I have been part of the consortium since my junior years as faculty…It is a wonderful experience to work together with my colleagues from all the other institutions. One of the strengths is the collaborative nature of our work together. The mission of the steering committee is to create a highly functioning infrastructure based on collaboration, with the final goal of developing clinical trials that are activated in a very timely manner and offer the ability to enroll patients in an active and efficient way.

The Big Ten CRC Steering Committee has put together several initiatives. This is the committee that puts together the policies that adjust the infrastructure guiding how the Big Ten [CRC] functions. One of the strengths is offering senior mentorship throughout the years. We encourage junior investigators from one institution to work together with senior investigators from other institutions, and that has been tremendously successful in several ways: first, by mentoring junior faculty, and second, by having more institutions committed to a given trial from time zero. That leads to a very successful trial overall.

We are also looking at centralizing the review process. When we look at scientific review and institutional review boards [IRBs], every one of these steps [adds] time to activation, and the steering committee has been working very carefully toward centralizing this process, which ultimately expedites trial activation.

How has the profile of patients with breast cancer entering phase 1 trials changed in recent years, especially with antibody-drug conjugates [ADCs] and newer targeted agents in later lines of therapy?

Phase 1 trial participants come with very selective characteristics. Traditionally, patients participate in phase 1 clinical trials after they have gone through multiple lines of therapy and reach a point where standard of care is no longer available.

What we have seen in the breast cancer space, and in many other disease sites, is tremendous growth in new agents available for our patients. With that, we have so many lines of treatment for patients with breast cancer. If we stick with the traditional approach of enrolling patients in phase 1 studies after multiple lines of treatment, we risk not being able to offer those trials to our patients.

A strategy for enrolling patients in phase 1 trials is to look at their disease characteristics. Ideal patients for phase 1 trials are those with longer stability of their disease. Patients whose tumors are growing or progressing rapidly are generally not great candidates for phase 1 trials. Ideally, you want someone who has time on study so you can see how they react to these new agents. Phase 1 trials are looking at safety, and to do that, you need some stability in their disease.

What has changed is that we are bringing phase 1 trials earlier in the course of treatment for our patients because we need to maximize our chance to look at investigational agents earlier on vs waiting until late stages of the disease. That requires a strategic approach to enrolling and selecting patients for phase 1 trials.

How has dose optimization, such as through the FDA’s Project Optimus, changed the way you run phase 1 studies?

That was an initiative from the FDA several years ago that looked at the traditional design of phase 1 trials. We have moved somewhat away from the so-called 3 + 3 design, with the idea that we want to maximize patients’ ability to be treated in phase 1 trials while also giving them the chance to reach the dose that would eventually be effective for them.

Phase 1 trials are designed by a collaborative team that includes a statistician and the principal investigator. It is not one approach for all trials. We customize based on the type of agent we are studying and what we know about that agent from the preclinical data. The goal is to have fewer patients at a suboptimal dose. We do not want to expose too many patients to a dose that will not be efficacious, and we also want to minimize adverse effects and toxicity for these patients. We want less risk. With that, we have switched toward adaptive statistical designs to reach an efficacious dose in an expedited way while making sure safety is assured.

What are the biggest operational barriers to opening and enrolling early-phase trials today, and how are they being addressed?

When we look at opening clinical trials in general, and specifically phase 1 trials, there are new regulations and multiple steps in the process. Contract and budget negotiations between sponsors and institutions tend to be more complex nowadays, especially for a multi-institution trial.

Looking early on at the trial design, at its goal, and at how many institutions are involved tends to make the process more efficient; [you must have] very close communication among sponsors, investigators, and institutions that have a strong research infrastructure. It does not have to be only those with historical capabilities; newer institutions are great in their ability to support phase 1 trials. The key is knowing ahead of time what the infrastructure is and who is in charge, along with clear communication.

What really expedites the process once a trial is open is making sure the investigators and sponsors meet regularly. We generally have weekly meetings with updates on patient enrollment: How are patients doing? When do we escalate? Planning ahead and close communication are the first strategies to improve this.

You have also studied disparities in estrogen receptor–positive breast cancer. How do you make phase 1 trials more accessible to underrepresented patients?

The University of Illinois Cancer Center primarily serves an underserved patient population, and we are fortunate to offer these patients novel agents and new cancer treatments that they otherwise would not have access to.

To reach the community, we have a very strong community outreach and engagement program, and there is very close collaboration between our clinical trials office [CTO] and the community outreach and engagement office. We are able to promote our trials out in the community through that office, explain to patients what is available, and have our investigators discuss our trials with community members and community physicians. That has been very successful in bringing patients to our institution for clinical trials.

Website design and clear information on our website about what is available also matter. We have several modules to educate patients about what is available, what a clinical trial is, and what an investigational trial is. There is very strong collaboration among everyone in our cancer center to bring these new agents to our community. It is very important that patients are aware, know how to access us, and know how to identify a trial that matches their disease.

Which novel mechanisms or drug classes in breast cancer are you most excited to see move from phase 1 trials into later-stage testing?

We have recently been fortunate in the breast cancer field because so many new drugs have made it out or are in development. I generally like to look at breast cancer by subtype: hormone receptor [HR]–positive, triple-negative, and HER2-positive disease.

CDK inhibition is something I am still very excited about. A lot of my work has been dedicated to CDK4/6 inhibition in the HR-positive subtype. Now, looking at more selective CDK inhibitors, such as CDK2 and CDK4 inhibitors, I am really excited to see these new agents and the role they will play in the breast cancer landscape. That is probably what I am most excited about.

Reference

Project Optimus: reforming the dose optimization and dose selection paradigm in oncology. FDA. Updated December 6, 2024. Accessed October 20, 2026. https://tinyurl.com/mryuc8zm