Meso Foundation Clinical Trial Consortium for Faster Advancement of Mesothelioma Research

by Lee M. Krug, MD

At the International Mesothelioma Interest Group Meeting in Boston, a group of investigators convened at a Clinical Trials Design Workshop to discuss the challenges of conducting trials in this disease. The rarity of mesothelioma poses various issues with regards to proper study design, accrual, and interest by pharmaceutical companies. One theme that emerged from that workshop was the need to establish a clinical trials consortium. This concept has been quite successful with other rare cancers such as pediatric tumors and sarcoma. I propose that the Meso Foundation would provide the optimal mechanism to initiate such a consortium for mesothelioma trials.

The Meso Foundation Trials Consortium (MFTC) would offer the following advantages:

  • It would provide scientific input to ensure that the trials are scientifically sound. The investigators involved in the Consortium best understand the biologic underpinnings of the disease. They would have important insight into the optimal design of the trials. Trials could be prioritized based on scientific merit and promise. This would ensure that valuable resources would not be wasted on trials unlikely to be successful.
  • It would establish an international network of participating institutions with the highest volume of mesothelioma patients. This would have drastic effects on speeding accrual to complete trials in a timely fashion. The vorinostat phase III trial took over 5 years to complete enrollment, despite enlisting 125 institutions in 23 countries. The majority of those sites enrolled only 1 or 2 patients over that time. Typically, pharmaceutical companies hire Contract Research Organizations (CROs) who identify sites to conduct trials and collect the data. CROs do not know which institutions will have the appropriate patients for the trial.
  • It would offer a referral mechanism to boost accrual. Patients look to the Meso Foundation as the primary source for medical advice, so they could be steered toward institutions that are participating in the designated studies.

Of course, the Meso Foundation does not have the resources to conduct clinical trials itself. The funding will initially need to come from the pharmaceutical industry. The process would work as such: Pharmaceutical companies interested in conducting large trials in mesothelioma would formulate an agreement to work with the Meso Foundation. Their protocols would be reviewed by a subcommittee of the Science Advisory Board who would provide feedback on the design and technical aspects. The Meso Foundation would solicit key institutions with strong research programs and high patient volumes to open the trial at their sites. Patients would be preferentially referred to these studies for participation. Once the success of this mechanism has been established, other companies will surely look to the Foundation for assistance. Ultimately, investigator-initiated trials could even be considered.

This year, more pharmaceutical companies than ever are planning clinical trials for patients with mesothelioma. This heightens the urgency to develop this consortium. As a research community, we cannot wait any longer. Let’s work together to make this happen.

Lee M. Krug, MD, is an Associate Attending Physician in the Division of Thoracic Oncology, Department of Medicine at Memorial Sloan-Kettering Cancer Center in New York, NY. Dr. Krug is also the Director of the Mesothelioma Program at Memorial Sloan-Kettering Cancer Center and Chair of the Science Advisory Board of the Mesothelioma Applied Research Foundation.

FROM THE MESOTHELIOMA APPLIED RESEARCH FOUNDATION’S “MEET THE EXPERTS” SERIES: Introducing a New Clinical Trial with Dr. Julie Brahmer

Tonight, as part of the “Meet the Experts” podcasts presented exclusively by the Meso Foundation, Dr. Julie Brahmer, Associate Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, sat down with Mary Hesdorffer, Nurse Practitioner and Medical Liaison for the Meso Foundation, to discuss her new trial targeting pleural mesothelioma. In her talk “NGR-hTTNF: A New Multi-Center Drug Trial for Pleural Mesothelioma”, Dr. Brahmer discussed a new chemotherapy treatment, designed specifically for pleural mesothelioma patients.

To participate in the trial, one prior treatment regimen is required (for example Alimta and Cisplatin) which usually consists of 4 to 6 treatments. The NGR-hTTNF trial can then be offered in the second line setting. Patients will receive an active chemotherapy agent, and plus or minus the experimental drug NGR-hTTNF. This trial is available worldwide. In the United States, it can be obtained at Johns Hopkins in Baltimore, Maryland, as well as a few others sites in Texas, California, and New York. According to Dr. Brahmer, it consists of a weekly treatment, with the most common side effects resulting in fatigue, nausea, headaches, and generalized weakness. The enrollment process into the NGR-hTTNF trial begins with an appointment with an investigator in trial.

The investigator reviews whether or not the patient is eligible based on treatments already received, the patient’s stage of mesothelioma, and his or her general physical well-being. Following this appointment, the patient must sign the consent form, after which eligibility is finalized through a few additional tests. If patients have responded positively or remain stable, chemotherapy will be discontinued after six cycles and patients will be extended an opportunity to receive NGR-hTTNF as a maintenance therapy. The primary end point of this trial will be to extend survival rates with secondary endpoints of improving quality of life and diminished symptoms of mesothelioma.

Having just returned from the annual Annual Meeting of the American Society for Clinical Oncology (ASCO) conference in Chicago, IL, where another expert from our “Meet the Experts” series — Dr. Lee M. Krug — gave his own summary of the event, Dr. Brahmer feels optimistic and excited about possibilities ahead. “I think a lot of the things we’re learning in lung cancer research may affect patients with mesothelioma,” she states. “There are some therapies being developed that stimulate the immune system, and I hope those types of drugs will have some type of role in combatting mesothelioma, as well.”

Dr. Brahmer’s research and clinical practice focuses on the development of new therapies for the treatment and prevention of lung cancer and mesothelioma. Dr. Brahmer has published several papers in this area of research and is a member of the American Society of Clinical Oncology and the Eastern Cooperative Oncology Group (ECOG) Thoracic Committee and Cancer Prevention Steering Committee. She is one of the founding Board members for the National Lung Cancer Partnership (formerly Women Against Lung Cancer). Within the National Lung Cancer Partnership she currently serves as a member and the Chairman of the Scientific Executive Committee. She serves on the medical advisory board of the Lung Cancer Research Fund and is a former member of the Mesothelioma Applied Research Foundation’s Science Advisory Board.

More information about this trial is available at the Meso Foundation by emailing mary@curemeso.org or by calling (703) 879-3820. If you missed tonight’s “Meet the Experts” presentation, you can replay Dr. Brahmer’s talk and find out more about our other mesothelioma research resources at curemeso.org.

FROM THE MESOTHELIOMA APPLIED RESEARCH FOUNDATION’S “MEET THE EXPERTS” SERIES: An Evening of Research Breakthroughs with Dr. Raffit Hassan

Tonight, as part of the “Meet the Experts” podcasts presented exclusively from the Meso Foundation, Dr. Raffit Hassan, Senior Investigator and Chief of the Solid Tumor Immunotherapy Section in the Laboratory of Molecular Biology at the National Cancer Institute (NCI) and former Chair of the Meso Foundation’s Science Advisory Board, sat down with Mary Hesdorffer, Nurse Practitioner and Medical Liaison for the Meso Foundation, to discuss his research into mesothelin and development of  clinical trials  using mesothelin as a target for epithelial malignant mesothelioma, providing both pleural and peritoneal mesothelioma patients with the potential of much-needed new treatment options.

In his talk “Mesothelin: A New Target for Immunotherapy” Dr. Hassan discussed the novel therapies for the treatment of mesothelioma. Laboratory investigation, carried out by Dr. Ira Pastan, Dr. Hassan, and colleagues at the NCI, has demonstrated that mesothelin, a tumor antigen which was discovered at the NCI, is a useful target for tumor-specific therapy of malignant mesothelioma. Morab 009, a chimeric anti mesothelin monoclonal antibody, has completed a multi center trial and we expect to hear the results at the Annual  ASCO Meeting taking place in early June. (American Society of Clinical Oncology).

This evening, in his talk, Dr. Hassan outlined the approval process by which patients can become part of this trial.

Good candidates for this trial are generally those patients who have already had some type of treatment. For example, patients who are not good candidates for surgery or those who have had surgery in the past and patients who have had at least Alimta-based therapy would be considered good candidates.

The first step is an initial screening, beginning with the patient’s doctor and then a face-to-face interview with Hassan, his team, and all data from the patient’s physician. If, following the initial tests, the patient is found a suitable candidate, NCI will help with travel expenses to enable the patient to participate in the trial. “At no time,” Dr. Hassan assured, “either in the initial screening or in the trail itself is the patient charged for treatments.”

Some side effects have included weight gain and leg swelling, mainly coming from fluid retention, and a decrease in albumin, a blood protein. However, Dr. Hassan commented, “These side effects usually disappeared by the time of the patient’s discharge from the hospital.”

More information about this trial is available at the Meso Foundation by emailing mary@curemeso.org or by calling (703) 879-3820.

Mesothelin, defined by MedicineNet.com, is a protein found on cell surfaces. Certain antibodies bind themselves to mesotheliomas and other tumors, so soluble mesothelin-related proteins (SMR) are used to identify mesothelioma patients and to monitor the cancer’s progression of their disease. SMR concentrations tend to run higher with mesothelioma patients than patients battling other cancerous or pleural diseases, and SMR concentrations often correlate with tumor size and progression.

A 2011 recipient of the Meso Foundation’s Pioneer Award for breakthroughs in mesothelioma research, Dr. Hassan has focused his own trials on targeting mesothelin as a potential treatment of patients with mesothelioma. Dr. Hassan’s research began in the NCI laboratory and continues to this day.

If you missed tonight’s “Meet the Experts” presentation, you can replay Dr. Hassan’s talk or download it as one of our podcasts at our website.