Lessons Learned from Running Clinical Trials in Rare Cancers

How to Accelerate Recruitment in Rare Tumor Studies

By Patricio Ledesma, Founder & CEO, Sofpromed

Throughout my career managing oncology clinical trials across Europe, North America, and Asia-Pacific, some of the most challenging studies I have worked on involved rare cancers.

These include (among others):

• Soft tissue sarcomas
• Bone sarcomas
• Ovarian clear cell carcinoma
• Endometrial serous carcinoma
• Pediatric leukemias
• Pediatric brain tumors

Many biotech companies assume that recruitment difficulties are unavoidable because the disease itself is uncommon.

My experience tells me otherwise.

While incidence certainly matters, poor planning is often a larger obstacle than rarity itself.

Over the years, I have seen rare cancer studies recruit ahead of schedule while others targeting more common tumors struggled significantly.

The difference usually comes down to strategy.

In this article, I would like to share the most important lessons I have learned from running rare oncology studies, particularly in sarcoma, gynecologic oncology, and pediatric oncology programs.

Why Are Rare Cancer Trials So Difficult?

Rare cancers present several recruitment challenges simultaneously:

For example, many soft tissue sarcoma subtypes represent only a small fraction of overall cancer diagnoses, and some individual sarcoma histologies may be encountered only occasionally even in large referral centers.

Similarly, rare gynecologic cancers are often concentrated within specialized academic networks.

Pediatric oncology studies face an additional challenge: investigators must balance research participation with very strict safety and ethical requirements.

Lesson #1: Inclusion and Exclusion Criteria Can Make or Break Recruitment

This is probably the most important lesson I have learned.

Many protocols unintentionally exclude patients who could safely participate.

A biotech company may spend years developing a promising therapy, only to discover that only a small proportion of real-world patients qualify.

I always encourage sponsors to evaluate:

• How many patients are lost because of laboratory thresholds?
• How many are excluded due to previous therapies?
• How many fail because of arbitrary washout periods?
• Are all exclusion criteria clinically justified?

I have seen studies reduce projected enrollment timelines by months simply by revising overly restrictive criteria.

Example

Instead of:

"Patients must have received exactly one prior line of therapy."

Consider:

"Patients must have received one or more prior lines of therapy."

That simple modification can dramatically increase the eligible population.

Lesson #2: Conduct Feasibility Assessments Using Actual Patient Data

One of the biggest mistakes in rare oncology studies is relying on investigator optimism.

Almost every investigator believes they can recruit more patients than reality allows.

Successful feasibility requires:

• Historical patient counts
• Molecular subtype prevalence
• Competing trial assessment
• Referral network evaluation
• Screening failure estimates
• Geographic accessibility analysis

I always ask sites:

"How many patients meeting all protocol criteria were treated during the last 12 months?"

Not:

"How many patients do you think you can recruit?"

The first question generates useful data.

The second often generates wishful thinking.

Table 1. Recruitment Risk Assessment Framework

In my experience, studies with three or more "high-risk" categories almost always require additional countries, more sites, or broader inclusion criteria.

Lesson #3: Partner With Patient Advocacy Groups Early

This is one of the most underestimated opportunities in rare cancer research.

Patients with rare tumors are often highly engaged.

Many actively search for:

• Emerging therapies
• Expert centers
• Clinical trial opportunities
• Patient communities

Advocacy organizations can help raise awareness among patients and caregivers long before site activation.

Examples include:

• Sarcoma Foundation of America
• Sarcoma UK
• EURORDIS
• National Organization for Rare Disorders (NORD)
• Ovarian Cancer Research Alliance
• St. Baldrick's Foundation

When sponsors collaborate appropriately with advocacy groups, study awareness often increases substantially.

I have personally seen patient organizations become one of the most effective recruitment channels in rare cancer programs.

Lesson #4: Focus on Centers of Excellence

Many sponsors attempt to open large numbers of average-performing sites.

In rare cancers, this strategy often fails.

For sarcoma studies, I would much rather activate:

• 20 highly specialized sarcoma centers

than

• 80 non-specialized oncology sites.

The same principle applies to:

• Pediatric oncology
• Ovarian cancer
• Endometrial cancer
• Rare molecular tumor subtypes

Expert centers see concentrated patient volumes and maintain extensive referral networks.

Table 2. Typical Recruitment Performance by Site Type

For rare oncology studies, site quality almost always matters more than site quantity.

Lesson #5: Open Countries Strategically

Sponsors sometimes select countries based on regulatory convenience alone.

For rare cancers, patient availability should drive country selection.

Key considerations include:

• Established referral systems
• National cancer networks
• Rare tumor registries
• Investigator reputation
• Existing advocacy infrastructure

Countries frequently performing well in rare tumor studies include:

This is especially true for sarcoma research, where patients are frequently referred to national reference centers.

Lesson #6: Use Centralized Pre-Screening Programs

Many patients never reach clinical trial sites because they are never identified.

One highly successful approach involves:

• Central molecular screening
• Referral databases
• Early patient identification
• Registry partnerships

Sponsors who implement centralized pre-screening initiatives often identify eligible patients months earlier than traditional recruitment methods.

Lesson #7: Molecular Eligibility Can Become the Biggest Bottleneck

Precision oncology has transformed cancer drug development.

However, biomarker-driven eligibility can significantly reduce the available population.

Consider a hypothetical scenario:

This illustrates why protocol assumptions frequently overestimate recruitment potential.

The pool shrinks at every stage.

Lesson #8: Speed Matters

In rare oncology studies, delays are particularly damaging.

A three-month delay in activation can mean:

• Missed referral opportunities
• Patients enrolled into competing studies
• Lost investigator momentum

That is why I strongly recommend:

• Accelerated feasibility
• Early contracting
• Faster ethics submissions
• Rapid site activation
• Proactive recruitment planning

The most successful rare cancer trials begin recruitment activities long before first-patient-in.

Practical Strategies That Consistently Improve Enrollment

Table 3. What Works Best in Rare Cancer Recruitment

My Top 10 Recommendations for Sponsors

If I were advising a biotech company preparing a rare oncology study tomorrow, I would recommend:

1. Design recruitment-friendly eligibility criteria.
2. Challenge every exclusion criterion.
3. Conduct feasibility using actual patient data.
4. Prioritize expert referral centers.
5. Engage patient associations early.
6. Develop country-specific recruitment strategies.
7. Understand competing trial activity.
8. Invest in centralized pre-screening programs.
9. Activate sites rapidly.
10. Continuously monitor recruitment assumptions.

Final Words

Having worked on numerous rare cancer studies, particularly in sarcoma, gynecologic oncology, and pediatric oncology, I have learned that rarity itself is not the main reason trials fail to recruit.

The real challenges are usually operational.

Protocols become too restrictive.

Feasibility assessments become too optimistic.

Patient advocacy groups become an afterthought.

Referral networks are underestimated.

The sponsors who succeed are those who plan for recruitment strategically from day one.

In my experience, the winning formula for rare cancer trials is straightforward:

Develop realistic eligibility criteria, perform data-driven feasibility assessments, partner with patient advocacy organizations, select true centers of excellence, and identify potential patients as early as possible.

When these elements are executed well, even studies targeting very rare tumor populations can recruit efficiently, deliver high-quality data, and bring innovative therapies to patients much faster.