Launched in 1997, our Clinical Trials Office incorporates experts conducting clinical trials at the Vall d’Hebron University Hospital’s (HUVH) Medical Oncology Department, the Vall d’Hebron Barcelona Hospital Campus. Headed by VHIO’s Director, Josep Tabernero, our team comprises study coordinators, data managers and administrative who coordinate phase I–IV clinical studies and also participate in several translational research projects at VHIO. Organized into 4 groups (start-up unit, oncology study coordinators, oncology data entries, hematology study coordinators and data entries) covering all tumor types and studies, our personnel are managed by the Clinical Trials Office Director, Marta Beltran.
Clinical Trials in Oncology
In 2020 we managed 2 phase 0, 169 Phase I, 26 Basket studies, 148 phase II, and 129 phase III clinical trials with active recruitment throughout the year (Figure I), with patient enrolment totaling at 1084 (Figure II). 178 new trials were initiated, including 7 post-authorization trials, and rollover studies. In addition, we continue to follow up patients who were recruited prior to 2020 and are still enrolled and receiving study treatment (more than 800 patients in total, and more than 1700 in follow -up).
More than half of our patients included in our Phase I Clinical Trials have been referred to us from other Hospitals, which has consequently positioned our Unit as leading reference in early clinical studies. As a reflection of our continued expansion as well as recognition of excellence, VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch directed by Elena Garralda, has been re-accredited by the Generalitat de Catalunya – Government of Catalonia.
As we continue to render personalized medicine more precise by matching therapies to respond to the specificities of each individual patient, each individual tumor, the requirements and selection criteria for inclusion in certain studies are also becoming more complex.
While we are dedicated to expanding our portfolio of trials in order to ultimately establish new treatment models with highly selective drugs, we continue to fine-tune patient selection criteria in order to best identify those patients who are most likely to benefit from novel therapies, including emerging immune-based therapies, tailored to individual patients’ molecular ‘measurements’.
Clinical Studies in Hematology
In 2020 we managed 39 Phase I, 36 phase II, and 45 phase III clinical trials with active recruitment throughout the year (Figure III) with patient enrolment totaling at 153 patients (Figure IV). 50 new trials were initiated, including 7 post-authorization trials, and rollover studies. In addition, we continue to follow up patients who were recruited prior to 2020 and are still enrolled and receiving study treatment (more than 122 patients in total, and more than 74 in follow-up).
The prestige of HUVH's Medical Oncology Department, led by VHIO's Director, Josep Tabernero, is increasingly recognized by pharmaceutical as well as biotechnology companies. It has also become a reference program and selected by the industry to carry out complex clinical trials for which the number of participating centers is highly restricted.
Clinical sites are selected based on the highest standards of quality and capacity for carrying out state-of-the-art research. We have participated in early phase trials of different drugs, ultimately enabling the pharmaceutical industry to market novel anti-cancer medicines. We are involved in studies promoted by the pharmaceutical industry as well as those developed by us in collaboration with other hospitals. We have also conducted more than 10 Investigator-Initiated Trials (IITs) in oncology.
Contribute to the development of novel therapies against cancer.
Consolidation as an international reference for clinical trials in oncology and hematology.
Guide patients enrolled in clinical trials to comply with the protocol requirements and help them with daily life throughout the duration of their participation.
Standardize clinical trial processes to ensure optimal quality and the compliance of Good Clinical Practice (GCP).
We continue to report important numbers of clinical trials performed and respective patient recruitment.
Appropriate management of the complexity of protocols which are increasingly demanding.
We have provided tailored training for our staff in order to further improve the quality of our work and expand related skill sets.
Implementation of new tools and procedures to increase the quality and efficiency of research.
Reorganization of the clinical trials office to implement transversal work
Reorganization during the Sars-CoV-2 pandemic to guarantee the continuity of treatments while maintaining quality standards.
Adaptation of monitoring systems to achieve remote source data verification by 2021.
RESEARCH UNIT FOR MOLECULAR THERAPY OF CANCER (UITM) – CaixaResearch
Inaugurated in June 2010, thanks to the support received from the ”la Caixa” Foundation, the Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch is dedicated to complex clinical trials with drugs in early development (phase I and early phase II trials), focusing on novel targets. Occupying a total surface area of 1000 m2 our Unit is located within the General Area of the Vall d’Hebron University Hospital (HUVH), the Vall d’Hebron Barcelona Hospital Campus.
This privileged environment with direct access to patients, coupled with VHIO’s translational approach to research and superb scientific framework, has enabled our Unit to rapidly establish itself as one of the few comprehensive facilities in Europe to rapidly transform latest discovery into benefits for patients.
By promoting tight connectivity between oncology care and research we establish novel treatment models for patients with highly selective drugs, and advance insights into tumor diseases and how to treat them in an individualized way – getting the right therapy to the right patient at the right time. As the figures show, we are gradually doing so for an increasing number of patients.
This year has been particularly challenging due to the COVID 19 pandemic. All our efforts have focused on successfully maintaining our clinical research activities and continuing to include patients in our clinical trials. During 2020, our Unit participated in 195 ongoing phase I clinical trials, 26 of which are Basket trials (a 20% increase compared with 2019). Our facilities, coupled with our multidisciplinary clinical teams, enable us to continue to expand our portfolio of phase I studies. This year we opened 71 new trials; 4 as Baskets, with 521 patients enrolled.
Research carried out at our Unit by VHIO’s Early Clinical Drug Development Group, directed by Elena Garralda, centers on the development of new drugs based on the molecular profile of each tumor as well as the optimization of treatment regimens using combinations of new agents with those that already exist.
Reflective of VHIO’s purely translational model, our studies are also linked to several research lines led by other VHIO groups, thus connecting molecular biology and optimal tumor models with pharmacology and innovative clinical research. VHIO scientists also collaborate closely in our trials to facilitate biomarker development, a deep understanding of the mechanism of action, as well as research into mechanisms of cancer drug resistance.
We also participate in VHIO’s Molecular Prescreening Program, that performs molecular analyses of patients’ tumors to select the best possible treatment with the experimental therapeutics available. Thanks to our Cancer Genomics Group’s, the development of existing applications for faster results including an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and two NextGen Sequencers; MiSeq and HiSeq2500 (Illumina), enable us to drive faster and more precise mutational analyses of tumor suppressor genes as well as translocations and gene amplifications.
UITM – CaixaResearch incorporates a multidisciplinary team comprised of medical oncologists, clinical trial coordinators and data managers, nurses and nurse technicians, pharmacists, as well as administrative personnel.
Excellent patient treatment and care as well as pioneering research is also made possible thanks to the collaboration of many other oncology professionals including our team of Clinical Research Oncology Nurses led by Mª Angeles Peñuelas, pathologists from the Vall d’Hebron University Hospital’s Molecular Pathology Department, radiologists and interventional radiologists, our Clinical Trials Office, directed by Marta Beltran, Database Management, Clinical Research Oncology Pharmacy Unit headed by Maria Queralt, our Quality & Processes Unit, managed by Gemma Sala, as well as many other healthcare specialists including dermatologists, cardiologists, and ophthalmologists.
Early clinical drug development and translational research led by UITM – CaixaResearch clinical investigators and VHIO researchers: expansion of our broad portfolio of promising novel anticancer therapies, across a balanced spectrum of studies, with special focus on first-in-human studies, novel-novel combinations, best-in-class compounds, and a new class of drugs.
Perform complex trials such as organ dysfunction trials, Octopus as well as Basket studies, and link clinical research at UITM to VHIO's preclinical and translational projects. Our Unit also collaborates with the various partners involved in drug development and translational research.
Genomic medicine trials in early drug development: perform molecular analysis of patients' tumors in order to select the best possible treatment with the experimental treatments available, co-develop medical informatics applied to genomic medicine, and integrate preclinical and clinical research by incorporating novel drugs, new insights, and study design together with customized molecular diagnostics.
Immunotherapy: our Unit's Task Force in early drug development of immunotherapeutics and cell signaling focuses on second generation immunotherapies, including new cytokines, bispecifics, intratumoral agents, immunomodulatory, and immune checkpoint inhibitors and combinations, as well as translational research in immuno-oncology.
We have performed some of the most complex phase I trials, including those focused on molecularly-selected patient populations (trials in complex molecularly-selected patient populations Basket/Octopus trials) as well as trials in immuno-oncology.
We have expanded our expertise in drugs targeting developmental pathways, cell signaling (ERK, MET, FGFR, RET, NOTCH, NTRK), and immunotherapy (LAG3, TIGIT, OX40, CD40, IDO, arginase inhibitors and engineered antibodies).
Developed by VHIO's Cancer Genomics Group, PI: Ana Vivancos, we benefit from applications for faster results including an n-Counter (Nanostring) platform, two digital PCR platforms (BEAMing Sysmex and ddPCR, BIO-RAD), and two NextGen Sequencers; MiSeq and HiSeq2500 (Illumina). We also co-develop customized molecular tests for VHIO's Molecular Prescreening Program: disease-oriented mutation panels for our NGS platforms.
We have successfully implemented the Basket of Baskets (BoB) trial which is a novel study in personalized medicine integrating cutting-edge molecular prescreening, the development of new diagnostic tests such as circulating DNA or Nanostring, with the testing of targeted therapies in populations of patients with identified molecular alterations in their tumors and a high probability of benefiting from the selected treatments. This is an academic study, endorsed by the Cancer Core Europe (CCE) Consortium, and co-funded by pharmaceutical companies. We are engaged in ongoing and advanced negotiations with pharmaceutical companies to increase the number of modules.
We have introduced Molecular Tumor Board meetings to discuss the most relevant genomic features of complicated cases to evaluate possible treatment options.
We have started an advanced cell-based therapy program, and are participating in several pharma sponsored trials to evaluate the role of TIL therapy as well as exploring an academic TIL product in collaboration with Alena Gros, PI of VHIO’s Tumor Immunology & Immunotherapy Group.
Clinical trials in oncology are essential for the identification of novel, more effective targeted therapies against cancer as well as improving survival, side effect profiles and the quality of life of patients. Advances in oncology care and the development of more powerful anti-cancer medicines are driven by optimal processes in clinical trials.
Our expert clinical research oncology nurses assume a central role by undertaking a variety of roles including identifying trends in side effects, closely collaborating with multidisciplinary teams to develop and evaluate patient management, contributing to clinical studies by collating samples and quality data, as well as providing excellence in nursing care and symptom management for all patients enrolled in clinical trials.
While the COVID-19 pandemic naturally presented new challenges which demanded adaptive procedures, structures and where possible, our clinical teams and oncology nurses had, in many cases, to re-think conventional patient care.
With the safety of our patients as the highest priority, Angeles Peñuelas led her team in working tirelessly together with VHIO’s medical oncologists and clinical investigators to swiftly establish adaptive circuits
and approaches to ensure the optimal running of clinical studies, while delivering, as always, the highest levels of quality patient care. Newly introduced measures in response to COVID-19 –whenever/wherever possible- included remote monitoring as well as dispensation of medication for certain patients receiving orally administered therapies, and telematic clinical consultations.
Supporting these teams comprised of medical oncologists, molecular pathologists, oncology pharmacists, clinical researchers, and study coordinators, VHIO's oncology nurses are key to ensuring the delivery of optimal care for patients who receive the full range of expertise, guidance, and the necessary follow-up throughout the course of their participation in a clinical study. As importantly is the psychological support they provide, alongside the other superbly trained oncology care givers and specialists including psychologists.
Our nurses also provide patients and their families with the information and professional guidance they need to make fully informed decisions concerning their treatment options. In 2020, across the 474 actively recruiting trials in oncology patient enrollment totaled at 1084. Regarding clinical studies in hematology, across the 120 trials, a total of 153 patients were enrolled. Our clinical teams also continue to follow up patients that were recruited prior to 2020 who are still enrolled and receiving treatment.
As VHIO continues to expand its portfolio of clinical trials to ultimately establish novel treatments with highly selective drugs, and fine-tune patient selection criteria in order to identify those patients who are most likely to benefit from them, we can expect a steady increase in patient recruitment across our clinical studies in the future.
Clinical Research Oncology Pharmacy Unit
Maria Queralt Gorgas
Clinical Director of the Clinical Research Oncology Pharmacy Unit
Our Unit is ISO 9001:2015 certified and is part of the Medical Oncology Department of the Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus. As noted in our highlights above, it is thanks to the funding received from the ”la Caixa” Foundation, that our new Facility, the Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch- Clinical Research Onco-Hematology Unit opened this year. Equipped with all the very latest technologies, it enables us to provide even higher quality in pharmaceutical care and continue to respond to all regulatory requirements.
We focus on two main areas of clinical research
Oncology Pharmaceutical Care Program
Our team of expert pharmacists are specialized in hospital and oncology pharmacy. The Unit’s laboratory technicians prepare cytostatics and other parenteral therapies used in clinical trials, as well as closely monitor and follow-up our patients.
Pharmacological Research in Oncology Support Program
This program is directed by our team of pharmacists and laboratory technicians specialized in clinical trials. They are responsible for the management of study supplies including storage, dispensation, and traceability control.
In 2020 they managed drugs used in 591 active clinical trials in oncology & hematology, and 10,748 resupply deliveries/clinical trial supplies receptions. Our cutting-edge system for controlling storage temperature -performing electronic temperature recordings every 5 minutes daily- displays readings on computers equipped with audiovisual alarms as well as an around-the-clock SMS alert system for monitoring and reporting temperature deviations.
Regarding the design and validation of our Unit’s drug preparation process traceability system, we ensure qualitative and quantitative quality control of our computerized system.
In 2020 our dispensing staff actively participated in 240 pre-study visits, 245 initial visits, 1,850 monitoring visits, 180 close-out visits, and also successfully passed 5 audits, and 1 ISO inspection.
Additionally, 44,136 clinical trial drugs have been dispensed and validated by our pharmacists, 13,044 of which were for oral administration, 984 for IM/ subcutaneous administration, and 30,108 for IV administration. A total of 204 Standardized Dispensing Procedures for clinical trials have been drawn up and we have performed 684 updates of these procedures due to subsequent amendments to protocols or pharmacy manuals. 156 storage temperature data reports have also been prepared by our dispensing team.
Preparations of cytostatics, monoclonal antibodies and other parenteral antitumor drugs for clinical trials totaled at 30,108. We also included 392 antineoplastic therapeutic schedules in our prescription software.
Our Pharmaceutical Care Program for patients enrolled in phase I clinical trials: we performed 1,248 visits, 348 screenings, 450 C1D1s, and 450 follow-ups, also compiling patient diaries and/or instructions for patients (in the absence of documentation provided by the respective sponsor).
We have also compiled 20 different diaries and 28 instruction manuals for patients enrolled in the phase I studies involving orally administered drugs by our preparation staff. We also prepared 24 diaries and 80 patient manuals for phase II and phase III clinical trials in 2020 for patients enrolled in all phase II and III studies involving orally administered drugs by our dispensing staff.
Excellence in the services that we provide to clinical oncology research programs through optimal efficacy, efficiency and safety.
Management, dispensing, preparation and administration of clinical study drugs according to protocol specifications. Ensure traceability of the entire circuit with the development and implementation of new software.
Maximized control of storage temperature of samples and preparations.
Optimal use of a computerized program, IPharma-FUNDANET®, for the management of clinical trial supplies.
Provision of a pharmaceutical care program for patients in phase I studies treated with orally administered medicines to improve safety, compliance and the efficacy of these therapies.
Provide instructions and indications to patients for orally administered therapies in phase II
and III studies.
Successful sponsor audits as well as inspections carried out by regulatory authorities.
Thanks to the support received from the ”la Caixa” Foundation, we moved into our new facility, the Research Unit for Molecular Therapy of Cancer (UITM) – CaixaResearch- Clinical Research Onco-Hematology Unit. Equipped with cutting edge technologies, it enables us to provide even higher quality pharmaceutical care and continue to meet all regulatory requirements.
Replacing paper medical orders, we have implemented electronic prescription ordering for IV administration medication in our site prescription software.
We have developed new traceability software that includes global pharmacotherapeutic processes; the prescription, validation, dispensing, preparation and administration of drugs in the oncology and hematology clinical trial setting.
Our Unit provides clinical and technical support for the prescription, preparation, and administration of cytostatics in clinical trials, as well as e-records of usage and timings.
Qualitative and quantitative quality control of all parenteral anticancer preparations to guarantee patient safety and protocol compliance.
ISO9001:2015 certification renewed. Successful sponsor audits, regulatory inspections, and participation in the renewal of VHIO’s Phase I Unit reaccreditation.
Molecular Prescreening Program FERO Foundation Advanced Molecular Diagnostics Program (DIAMAV)
Head of Program
VHIO's Molecular Prescreening Program, driven by-FERO’s Institutional Advanced Molecular Diagnostics Program (DIAMAV), catalyzes precision medicine at VHIO. Over the last decade, DIAMAV has provided access to advanced molecular diagnostics to more than 5,000 cancer patients, and is critical in matching targeted therapeutic approaches with hundreds of clinical trial opportunities.
This program, also counting on the support and expertise provided through our Research Unit for Molecular Therapy of Cancer (UITM), funded by the ”la Caixa” Foundation and directed by Elena Garralda, is led by Rodrigo Dienstmann (PI of Oncology Data Science – ODysSey – Group), and is based on the activity of VHIO’s Cancer Genomics Group headed by Ana Vivancos, and Molecular Oncology Group directed by Paolo Nuciforo, in collaboration with our Early Clinical Drug Development Group also led by Elena Garralda.
The main objective of the program is to facilitate clinical implementation of emerging cancer biomarkers that help optimize the selection of therapies for patients being considered for enrolment in clinical trials. Our program guides clinicians in selecting novel anti-cancer treatments and facilitates clinical-molecular correlative research at VHIO. Diagnostic tests are developed and validated in-house for the cost-effective and streamlined identification of tumor molecular alterations of major interest in drug development.
Tumor profiling includes a variety of genomic techniques including next-generation sequencing panels for the detection of mutations, copy number variations, gene fusions and RNA expression signatures, as well as histopathological techniques such as immunohistochemistry (IHC) and in situ hybridization (ISH) for protein and gene expression profiling.
In 2020, we have performed tumor molecular profiling in over 1,100 cancer patients that are candidates for enrolment in clinical trials. In total, around 150 patients were treated with biomarker-matched innovative therapies as a result of these efforts.
Interpretation of next-generation sequencing tests and educating clinicians on emerging biomarkers is another of our priority areas. During Molecular Tumor Board and Genetic Tumor Board meetings, we facilitate data exchange among a broad range of experts for the review of patients’ medical histories and cancer molecular profiles in order to more precisely guide treatment decisions and preventive measures.
Clinical implementation of advanced molecular diagnostics to optimize the selection of therapies for patients being considered for enrolment in clinical trials.
Continued medical education on emerging cancer biomarkers for precision cancer therapy.
VHIO is an active member of the AACR Genomics Evidence Neoplasia Information Exchange (GENIE) project, a multi-phase, multi-year, international study that catalyzes precision oncology through the development of a regulatory-grade registry aggregating and linking clinical-grade cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at the participating institutions.
PI paper pick
Dienstmann R, Garralda E, Aguilar S, Sala G, Viaplana C, Ruiz-Pace F, González-Zorelle J, Grazia LoGiacco D, Ogbah Z, Ramos L, Mancuso F, Fasani R, Jimenez J, Martinez P, Oaknin A, Saura C, Oliveira M, Balmaña J, Carles J, Macarulla T, Elez E, Alsina M, Braña I, Felip E, Tabernero J, Rodon J, Nuciforo P, Vivancos A. Evolving landscape of molecular prescreening strategies for oncology early clinical trials. JCO Precis Oncol. 2020. 4:505-513.
Quality & Processes Unit
Headed by Gemma Sala, formerly Director of VHIO’s Clinical Trials Office, VHIO’s Quality and Processes Unit was established this year, 2020, in order to further improve quality and unify processes in clinical trials carried out at VHIO. Our Unit is made up of quality, and transversal support teams including sample management and schedulers.
At VHIO we run numerous tasks related to clinical trials. It is therefore imperative that all these activities - and the personnel who perform them- are carried out by assuring optimal quality and excellence, and that the processes governing them are both homogeneous and the very best.
Quality is key to correctly performing clinical trials. Guaranteeing that all the current regulations of these studies be complied with is therefore essential. These homogeneous efforts follow Good Clinical Practice (GCP) guidelines, with the safety of patients as the top priority throughout.
Cross-support and common clinical trial tasks including scheduling, sample management, and the direction of quality and processes.
Collaborate with all teams participating in our clinical trials, detecting non-conformities and making improvements from the very outset.
Promote prevention versus correction to ensure that the methodologies and improvements implemented.
Successfully pass all audits and site inspections.
Standardize processes and generate a good flow of communication between teams, as a key operating element.
Carry out periodic and predefined quality controls, relating to documentation, circuits and procedures.
Conduct regular training sessions to review and further enhance quality.
Renew and improve the implementation and development of the Government of Catalonia’s Certification of VHIO’s Research Unit for Molecular Therapy of Cancer (UITM) – CaixaReasearch.
Develop and update Standard Work Procedures to standardize circuits, and provide all necessary trainings.
Clinical trials in oncology and hematology trials.
Our Unit collaborated in 500 active trials collectively enrolling a total of 1,200 patients. We have also monitored and managed over 200 patients receiving therapy each month, and successfully passed 18 audits and 1 inspection.