Q1: Briefly describe your background & experience, and how you came to work on the RAIDs project


Dr. Suzy Scholl: My first experience with the biology of cervical cancer was in Cambridge. Working as a junior doctor at the Addenbrookes clinic in the gynaecology and obstetrics department I also became involved in laboratory research under the supervision of Paul Farrell at the Ludwig Institute in Cambridge. Using Southern blot analysis we were able to demonstrate the integration of papillomaviruses in the tumor DNA. We have studied the incidence of HPV16 DNA in cervical tissue samples from patients with cervical carcinoma, severe dysplasias and normal controls. Five out of 11 invasive squamous carcinomas of the cervix, 3/4 dysplasias and 0/12 normal samples were positive in Southern blot assays for HPV16 DNA. Some of the tissue samples had as many as 500 copies of HPV16 DNA per cell. The amount of HPV16 DNA present correlated with the aggressiveness of tumour growth {Scholl, 1985}.
Subsequently, after joining Institut Curie in 1987, I became involved in vaccine clinical trials in breast cancer as well as cervical precancerous lesions (HPV vaccines in poxviral vectors) {Brun, 2011} while also pursuing translational research into the presence of the myelocytic compartment within tumors {Scholl, 1994}. With increasing knowledge on mutational aspects of cancers it became obvious that a large scale project integrating all these parameters was mandatory in order to allow a clearer vision of new alleys for therapy.


Q2: Please tell us about your position at Institut Curie and the involvement of your organization within the RAIDs project?


Dr. Suzy Scholl: I am a member of the clinical Oncology department and as such I have patient clinics where I see patients with early and late stage gynaecological and breast tumors. Institut Curie is a vast enterprise with many clinical trials mostly sponsored by industry, but the numbers of Curie sponsored trials is growing. The RAIDs project has been classified “top priority”; however this type of large scale project and its international dimensions are new to us. We have to rise to the challenge and constant adaptations are needed. While the brainpower of talented and creative academics is a principal contributor to clinical progress, new adaptations are needed to help creative developments such as platforms involving translational aspects (biobanking, electronic CRF) but also clinical trial methodology and supervision in different countries with different cultures and different visions. I am pleased to say that my colleagues from the gynaecology group take part in RAIDs, they recruit actively patients to our BioRAIDs trial, they accept to visit centres and exchange views and share expertise and they do find the experience very gratifying.

 

Q3: What are your expectations for the RAIDs project & for Institut Curie: (scientific  results, exploitable results, EU networking…)


Dr. Suzy Scholl: Basically my expectations are in all three domains.

  • Principally I would love to see improvements in the control of late stage disease. Cervical cancer being HPV driven (90%) but also showing mutations in the PI3KCA pathway in up to 40%, these are the principal targets to go for. It is my feeling that we shall have to adapt the micro environmental dysfunction in order to become more effective in antitumor vaccines. Checkpoint blockage is another very interesting aspect to be associated with vaccines, in particular since the viral antigen in cervical cancer is not a self antigen. Importantly, present standard therapies do not achieve complete clinical responses in patients with either PI3KCA pathway mutations as well as with tumor micro environment dysfunction (with “stromal signatures”).

  • Several small companies have been associated with this project with the aim to foster economic progress and we do hope that there will be exploitable results in terms of predictive markers of treatment success as well as new combinations of reagents. We have had so far little interest from larger pharma but that may change as we progress and have results to show.

  • The EU networking has taken on dimensions which I had not anticipated. It is a great pleasure to be able to interact with clinicians and biologists from many different centers. The networking in the gynae field has been broadened by the EORTC gynae group and I have been invited to participate in ENGOT as well as in International Gynaecology Cancer Society meetings.


Q4: As project coordinator, what are the most difficult or critical aspects of managing partners, and the most thriving aspects?


Dr. Suzy Scholl: The most difficult part is undoubtedly trying to avoid over feeding the partners with long emails while trying to feed the necessary information in a timely manner, leaving time for a reply. But there are deadlines to meet… Another aspect to which I had not given much thought is the inherent specificity of each partner and the relevance they see (or not) in an administrative task. Without specific help in their respective institutions they may find this interaction very challenging. Furthermore there is sometimes a gap between expectations and reality and the expectations cannot be turned into reality at the right speed.
The most thriving aspects are the great variety in opinions and “know how” and the excellent social and cultural interactions. We do learn from each other and by month 18 we do know each other sufficiently well to share expertise.


Q5: The RAIDs project comprises 2 targeted therapy based clinical trials and one multicenter European study. Can you please describe the challenges you faced in organizing the trials and how you believe the RAIDs experience can help future projects?


Dr. Suzy Scholl:
Ideally one would hope that the next large scale multicenter trial could be run through a single EU submission with one trial insurance. This is still in the planning stage. While setting up a “fool proof” biobanking system and installing all the necessary controls for the eCRF took us a little bit of (well spent) time, the regulatory/legal aspects between centers were trying and we have the feeling that we wasted a lot of time.
The two targeted therapy trials (antiviral reagent or HPV vaccine) are planned on a national scale in the Netherlands and in France. The problem here is the availability of the products for different reasons. But the outlook is good.
Finding other targeted reagents for patients who will not be in complete response following standard therapy remains an endless quest. One can wonder whether there might be a place for a greater flexibility between the EU and academic partners, including potential investors and drug companies through the creation of ‘micro enterprises”  allowing investigator sponsored trials into which the pharma companies contribute post phase 1 targeted reagents, free of charge and off licence.
Q6: Would you wish to participate in another European project?
Dr. Suzy Scholl: This project has definitely been and still is both very challenging and very exciting. The administrative part is immense; not so much as a result of the rather complex EU bureaucratic follow up but more to the fact that running a large clinical trial in several EU countries is extremely complicated due to constantly varying legal, regular as well as cultural and financial (trial insurance) aspects and I could not have faced those without the help of principal actors such as Maud Kamal from Institut Curie as well as the devotion of our clinical trials team and more recently with Ksenia Bagrintseva. We have gained experience, allowing to speed-up administrative as well as coordination tasks, thanks to the help of Alma.