Pharmaceutical Company Completes Enrollment for Phase 1B Trial for Mesothelioma

ResearcherIf you attended our International Symposium on Malignant Mesothelioma in March of this year, you may recall the buzz of excitement that coursed throughout the scientific sessions. This buzz sparked excitement throughout the entire mesothelioma community, as we discussed advances in science, the needs of those affected by this disease, and the work being done to spur the movement of drugs through the clinical trial process.

Recently, Aduro Biotech issued a press release announcing the completion of enrollment in the Phase 1b clinical trial of its novel immunotherapy, CRS-207. I took the opportunity to call and congratulate Steve Isaacs, the chairman, president, and CEO of Aduro Biotech, on his initial trial results and his plan to move this drug along quickly and offer it globally in the Phase 3 setting.

It is exciting to see plans to jump from a Phase 1b directly to Phase 3 based on what was agreed to be compelling data by the FDA.

Patients treated on the Phase 1b study received 2 doses of CRS-207, a vaccine that utilizes the listeria virus and mesothelin as a target to gain entry into the cell. Patients then went on to receive standard of care pemetrexed/cisplatin every three weeks for 6 courses. If patients were stable or responded to the aforementioned therapy, they were then placed on a maintenance regimen of vaccinations every 8 weeks until progression.

Interim data was presented at a large scientific conference and demonstrated that in the 32 evaluable patients treated on this clinical trial, disease control was observed in 94%, which included a 60% partial response, and 34% experiencing stable disease.

The study will remain open to chemotherapy naive patients (patients who have never received chemotherapy for their mesothelioma) while the plans for the Phase 3 trial continue.

To read more about the CRS-207 study results, click here. To listen to an interview that we held with Steve Isaacs regarding the CRS-207 clinical trial, click here.

Using Herbs and Dietary Supplements During Mesothelioma Treatment

SpicesOver the last several year or so, a number of people have posted information about various supplements they favor, both for general health and, occasionally, as specific alternative remedies meant to bolster cancer treatment or prevention.  A number of our mesothelioma warriors have used yoga or stretching regimens to aid in post-surgical tissue relaxation, and others employ meditation or focused cognition to aid in mood and pain management. These non-invasive techniques have conferred varying levels of positive results, and pose no particular interactive problems with standard oncology therapy. Others, however, use one or more complementary therapies (e.g., naturopathy, homeopathy) or supplements (e.g., ginseng, green tea extracts), which could cause interactions with standard treatment if the proper care is not taken. Here, we provide some reference material to help anyone considering using such therapies or supplements.

A wealth of reputable and relevant information is easily available. For example, the professionals at Memorial Sloan Kettering Cancer Center (MSKCC) have a botanical expert pharmacist who monitors current science regarding herbs, botanicals, and other supplements. This is part of MSKCC’s Integrative Medicine Services. More information is available here.

TALK TO YOUR PHYSICIAN
Some herbs and dietary supplements are known to be detrimental to standard cancer treatment efficacy. One thing all reliable sources agree upon is that, before you start using any form of supplement or complementary medical treatment, you should tell your physician what you are considering.

MSKCC writes: “It’s important to tell your doctor or another qualified professional that you are using a dietary supplement. The reason for this is that an active ingredient in the product could interact with — increase or lessen — the effect of other medicines you’re taking.  People undergoing treatment for cancer should not receive any dietary supplements unless they’re prescribed by a doctor or given as part of a clinical trial that’s received [IRB] approval.”

NCI, in its Complimentary Alternative Medicine material, agrees: “Tell your doctor if you’re taking any dietary supplements, no matter how safe you think they are. This is very important. Even though there may be ads or claims that something has been used for years, they do not prove that it’s safe or effective.”

MD Anderson is in line in this herbal supplements article: “[Y]ou should approach herbal supplements with caution and speak with your doctor before taking any, whether you’re considering a pill, capsule, tablet or liquid form.”

DO NOT RELY SOLELY ON LABELS OR PRODUCT CLAIMS
The second important thing each of these expert facilities makes clear is that supplements – including herbs, vitamins, manufactured powdered weight controls, steroids, and all other over-the-counter materials are unregulated. The FDA treats supplements as foods. This means it does not verify any label claims (other than prohibiting specific disease prevention assertions). These materials are not subjected to clinical trials as they are understood in pharmaceutical development, and there is no control over additives, purity or the production methods.

Some manufacturers’ studies assert benefits in cancer treatment from use of their supplements. However, these are not the randomized, double blind studies we know as the gold standard for scientific study of new therapies. NCI and the National Center for Complementary and Integrative Health have begun clinical trials on a limited number of complementary therapies, but that data is still in development. The list and overview of these studies is available here.

CONSIDER MODERATION
If your research and medical team’s review lead you to try any of the hundreds of supplements advertised as health support, it is sensible to begin with a minimum dose. If the herb or compound neither helps nor hurts, you can slowly increase the amount or frequency of use. A measured approach will give you, and the physicians checking your blood analyses and scans, a better opportunity to detect any adverse effects before they become severe. Similarly, you can determine whether positive effects are amplified by increased dosage.

REFERENCES
The following resources can provide you with additional information:

To read more about complementary and alternative medicine pertaining to mesothelioma patients, click here.

A Summary of Mesothelioma Studies from ASCO 2015

MicroscopeBy Hedy Lee Kindler, MD,  University of Chicago

The American Society of Clinical Oncology meeting was held from May 29 – June 2, 2015 in Chicago. About 30,000 attendees from across the world gathered to discuss the latest research advances in all types of cancer, making this the largest, most important oncology meeting of the year. This was a particularly exciting meeting for those of us interested in mesothelioma. I’ve summarized 3 of the most prominent studies below.

MAPS: A randomized trial of pemetrexed, cisplatin with or without bevacizumab. This oral abstract, presented by Dr. Gerard Zalcman on behalf of the French Cooperative Thoracic Intergroup (IFCT), was clearly the star of the show for those of us who care about mesothelioma. This study is important because it is the first randomized trial in over a decade to show that a new drug improves survival in mesothelioma patients. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), which is highly expressed on mesothelioma. Think of it as a drug that targets the blood vessels that feed tumors (angiogenesis). Bevacizumab (the trade name is Avastin) is already FDA approved in multiple cancers, including colon cancer and lung cancer. In the MAPS trial, all 448 patients received standard chemotherapy with pemetrexed plus cisplatin, and half of the patients were randomized to also receive bevacizumab with each dose of chemotherapy. After completing 6 cycles of chemotherapy, patients on the bevacizumab arm also received bevacizumab by itself, every 3 weeks until their cancer started to grow. The time for cancer growth to occur (progression-free survival) was about 2 months longer in the bevacizumab arm (9.59 vs. 7.48 months). Patients treated with bevacizumab also lived almost 3 months longer (18.82 vs. 16.07 months). The addition of bevacizumab did not make patients feel worse (it did not worsen quality of life), although it did cause increased side effects such as bleeding, high blood pressure, and blood clots. Because there was an improvement in survival with the experimental treatment, it is possible that this trial could lead to FDA approval of bevacizumab for mesothelioma—stay tuned!

NGR015: Randomized trial of investigator’s choice of chemotherapy with or without NGR-hTNF. Oral presentations at ASCO are only for the large randomized trials. At most ASCO meetings there are no mesothelioma presentations; this year, there were two! The second oral presentation was by Dr. Rabab Gaafar from Cairo, Egypt on behalf of an international group of investigators. All 400 patients on this trial previously received pemetrexed. They were randomized to receive either NGR-hTNF (another drug that targets angiogenesis) or placebo (sugar water).  In addition, patients could receive chemotherapy either with gemcitabine, vinorelbine, or doxorubicin, or no chemotherapy at all. Unfortunately, the addition of NGR-hTNF to chemotherapy did not affect how long the cancer was controlled, or how long the patients lived. Data is being analyzed to see if certain characteristics might predict which patients might benefit from this drug.

Mesothelin targeted immunotherapy CRS-207, plus pemetrexed/cisplatin chemotherapy. Dr. Raffit Hassan from the National Cancer Institute updated the results of this ongoing trial in a poster presentation. Mesothelin is highly expressed on the surface of mesothelioma. CRS-207 is a vaccine that increases the immune response against mesothelin, and may enhance the activity of chemotherapy. In this study, 2 doses of CRS-207 were given before pemetrexed and cisplatin, as well as after completion of 6 cycles of chemotherapy. Encouraging activity was observed: 60% of patients had tumor shrinkage, and another 34% had disease that did not grow. Thus 94% of patients had disease that was controlled with this experimental vaccine plus chemotherapy. This is much better than would be expected with chemotherapy by itself. Based on these encouraging results, a randomized study to test this combination compared with standard chemotherapy is in development.

Hedy Lee Kindler, MD, an internationally recognized authority on the treatment of mesothelioma, is a Professor of Medicine and the Director of the Mesothelioma and Gastrointestinal Oncology Programs at the University of Chicago. Dr. Kindler is a Past President of the International Mesothelioma Interest Group. She was a member of the Science Advisory Board of the Mesothelioma Applied Research Foundation from 2001-2014, and remains active with the Foundation.  Dr. Kindler chairs the Mesothelioma Subcommittee of the Alliance for Clinical Trials in Oncology, a national cancer clinical trials group. Her research focuses on the investigation of novel agents for the treatment of mesothelioma. Patients from throughout the United States come to Dr. Kindler’s Mesothelioma Clinic at the University of Chicago for her expert care and to participate in her many clinical trials. Dr. Kindler has been listed repeatedly in Best Doctors in America, America’s Top Physicians, America’s Top Doctors for Cancer, and Best Doctors in Chicago.

Updates from ASCO: CRS-207 Vaccine Study Results

MicroscopeAduro BioTech is conducting a clinical trial to test an investigational new immunotherapy for malignant pleural mesothelioma (MPM). This therapy, called CRS-207, is given to a patient in combination with chemotherapy in hopes of encouraging the body’s normal defense mechanisms to fight off the cancer. This trial aims to enroll up to 60 patients at 5 U.S. clinical sites. The company presented data at the American Society of Clinical Oncology (ASCO) conference this week showing that of the 32 patients with MPM treated with CRS-207 and chemotherapy, MPM tumors reduced in size for 19 patients, and tumors remained the same size (stable) in an additional 11 patients. CRS-207 is given prior to and after chemotherapy (cyclophosphamide, pemetrexed and cisplatin) for patients who have not received prior treatment or surgery for their disease.

If you are interested in participating in a clinical trial for this investigational new therapy, please click here.

The 2015 ASCO Annual Meeting, one of the largest oncology meetings of the year, was held from May 29 to June 2 in Chicago, Illinois. The Meso Foundation will be providing more information on studies presented at ASCO in the coming weeks.

LISTEN: Meet the Mesothelioma Experts Interview with Drs. Simone and Alley Now Available

Penn MedicineOn Thursday, May 14, the Meso Foundation interviewed Dr. Charles Simone and Dr. Evan Alley of the University of Pennsylvania Medicine during the Meet the Mesothelioma Experts series. The session was part of a series of interviews focusing on mesothelioma centers of excellence. Drs. Simone and Alley were interviewed by the Meso Foundation’s executive director, Mary Hesdorffer, with whom they discussed the mesothelioma program at the University of Pennsylvania Medicine.

The full interview is now available on demand on the Meso Foundation’s website at curemeso.org/experts.

Drs. Alley and Simone are the co-directors of the Penn Mesothelioma and Pleural Program. Dr. Alley is a medical oncologist and is the leading investigator in the PD-1 inhibitor trial that has recently made big news in mesothelioma. Read more about the trial here. Dr. Simone treats patients with malignant pleural mesothelioma with photon and proton radiation therapy and photodynamic therapy (PDT). He is a National Institutes of Health and Department of Defense funded investigator who performs clinical and translational research investigating the novel use of proton therapy and PDT as definitive therapy and as part of multi-modality therapy for mesothelioma.

As part of the Meet the Mesothelioma Experts series, the Meso Foundation invites specialists in the field of mesothelioma to discuss their current research interests as well as promising developments in the treatment of mesothelioma.

You can listen to this interview and other previous Meet the Mesothelioma Experts sessions at curemeso.org/experts.