Three NCT trials enter recruitment

RATIONALE: Precision oncology for rare cancers

Participating sites:
NCT Heidelberg, NCT Dresden, DKFZ, NCT Berlin, NCT SouthWest, NCT WERA, NCT West

Rare cancers are defined as diseases with an incidence of no more than six cases per 100,000 people per year. Taken together, however, they account for approximately 24% of all newly diagnosed cancers in Europe. Many of these diseases remain poorly understood biologically, making them difficult to treat clinically and often associated with an unfavorable prognosis.

The RATIONALE clinical trial investigates in a randomized design how comprehensive molecular analyses - including genome, transcriptome, and epigenome profiling - can be integrated into clinical decision-making for patients with rare tumors.

Approximately 950 patients will be enrolled over three years. A central component of the trial is a cross-site molecular tumor board in which experts from all six NCT sites and the DKFZ jointly develop treatment recommendations.

Prof. Stefan Fröhling (NCT Heidelberg), principal investigator (PI) of the trial, describes the objective:

“With RATIONALE, we aim to demonstrate that molecularly guided therapy can double progression-free survival in patients with advanced rare cancers compared with standard treatment.”

For Prof. Hanno Glimm (NCT Dresden), also a PI of the trial, the project also promises important structural insights:

“We are convinced that the innovative RATIONALE trial will generate new insights into rare tumors. For many patients who previously lacked treatment options for practical or economic reasons, we may now be able to make a real difference.”

Prof. Dominik Modest (NCT Berlin) emphasizes that such a structure can only succeed through close coordination across sites:

“The cross-site structure of the NCT with six locations offers clear advantages for this demanding research field. We combine the expertise of colleagues across sites, reach high patient numbers quickly, and can optimally involve patient representatives in both trial design and implementation.”

Molecular analyses generated at the participating centers are integrated within the trial workflow and evaluated rapidly.

Richard Schlenk, PI and Director of the NCT Clinical Trial Center in Heidelberg, describes the strength of this infrastructure:

“With our interdisciplinary teams, we can generate meaningful data from tissue and blood samples within four weeks and quickly recommend a tailored therapy to patients.”

RATIONALE is therefore not only a scientifically ambitious clinical trial but also a test of the NCT’s cross-site collaboration - from molecular diagnostics and tumor board structures to coordinated patient recruitment.

LEONORA: Systematically investigating quality of life after colorectal cancer surgery

Participating sites:
DKFZ, NCT Heidelberg, NCT SouthWest, NCT WERA, NCT West

While RATIONALE focuses on molecular precision in rare tumors, LEONORA addresses another clinically relevant aspect: quality of life after curative colorectal cancer surgery. Despite major advances in oncologic treatment, many patients experience long-term diarrhea, inflammation, or functional impairments that significantly affect their daily lives.

With 206 patients enrolled, LEONORA is the largest randomized placebo-controlled clinical trial worldwide and the first trial from Germany specifically investigating whether synbiotics can improve gastrointestinal quality of life after colorectal cancer surgery. In addition to clinical parameters, the trial also analyzes changes in the microbiome as well as immunological and metabolic markers.

Privatdozentin Dr. Lena Biehl, co-lead investigator of the trial, played a key role in developing LEONORA and oversees its implementation at NCT West in Cologne. For her, the start of recruitment marks the transition from conceptual work to clinical practice. Digestive problems or dietary restrictions are among the long-term consequences many patients experience after colorectal cancer surgery. Biehl explains the rationale behind the trial:

“Many patients experience digestive problems after such surgery or tolerate certain foods less well. We suspect that changes in the gut microbiota play an important role and that targeted restoration of the microbiome may lead to improvements.”

From the patient perspective, contributing to research is a central motivation. Trial participant Corinna H. says:

“If there is anything I can do that might help other patients in the future, I’m happy to take part in the trial.”

For the trial’s initiator and lead investigator, Prof. Ben Schöttker (DKFZ), the particular strength of the trial lies in linking a clearly patient-relevant quality-of-life endpoint with research into the underlying molecular mechanisms.

“Because our primary endpoint - gastrointestinal quality of life - is a patient-reported outcome, selecting a validated questionnaire and ensuring careful trial planning to obtain complete datasets are particularly important,” Schöttker explains.

The accompanying molecular research aims to clarify why improvements in patients’ quality of life occur. LEONORA therefore connects preclinical research with translational clinical research, focusing on an outcome that directly reflects patients’ everyday experiences.

A television feature on the LEONORA trial is available in the ZDF media library:
https://www.zdfheute.de/video/volle-kanne/probiotika-gegen-darmkrebs-100.html

DEPECA-2: Evaluating surgical innovation in penile cancer

Participating sites:
NCT SouthWest, NCT Berlin, NCT Dresden, NCT Heidelberg, NCT WERA

In penile cancer, approximately one third of patients develop lymph node metastases. The current standard treatment is open inguinal lymphadenectomy, in which the affected lymph nodes are surgically removed from the groin. However, this procedure is associated with severe complications in up to 50% of patients. Wound-healing disorders, infections, or prolonged recovery periods often delay further treatment.

DEPECA-2 is a randomized clinical trial investigating whether a robot-assisted surgical technique can significantly reduce complication rates while maintaining oncological safety. A total of 80 patients will be enrolled. The trial receives €1.8 million in funding through the NCT OCT2 program.

Trial leader Prof. Igor Tsaur (NCT SouthWest, University Hospital Tübingen) explains the clinical motivation:

“For many patients, not only the cancer itself but also the treatment represents a major physical and psychological burden. We therefore need new surgical approaches that maintain oncological safety while significantly reducing complication rates.”

At the WERA site, Prof. Bernd Wullich (University Hospital Erlangen) contributes his surgical expertise and welcomes the start of the trial:

“I am confident that the DEPECA-2 trial will be a game changer and that robotic techniques will eventually replace conventional lymphadenectomy.”

In addition to clinical endpoints, the trial also collects patient-reported outcomes to systematically evaluate complications, recovery time, and quality of life. Patient representatives were already involved during the development phase to ensure that the patient perspective was incorporated into the trial design from the outset.

Udo Ehrmann, board member of the German Prostate Cancer Self-Help Association (Bundesverband Prostatakrebs Selbsthilfe e. V.), participated as a patient representative in developing the trial protocol. He describes the process:

“I was invited to participate as a patient representative and reviewed the study synopsis and protocol from a patient perspective. I then discussed the identified areas for improvement with the trial initiators, and many of them were incorporated into the protocol. I consider this form of patient involvement very valuable; targeted training opportunities can further help patient representatives contribute their experiential expertise effectively.”

Additional patient representatives will be involved throughout the trial to further support its development.

From building structures to implementation

With RATIONALE, LEONORA, and DEPECA-2, the NCT demonstrates that its cross-site structure is effective. Six sites and the DKFZ collaborate in joint clinical trials, recruit patients nationwide, discuss cases in interdisciplinary settings, and actively involve patients as partners in research.

The first phase focused on building the structure.
Now the implementation is underway.