Mesothelioma Clinical Trials
Mesothelioma Clinical Trials
Until recently, clinical trials for mesothelioma were difficult to conduct. The disease had a rapid onset and progression, leading to a relatively short survival period in which to conduct clinical trials. Also, there was a lack of basic understanding about the clinical biology of the disease and how the disease changed during progression.
Specific clinical measures were difficult to obtain in order to demonstrate the response to treatment. Recently, as part of the Alimta clinical trial, researchers developed new metrics that included factors other than just pleural thickening or abnormal breathing capability. A number of new clinical trials are now underway, many of them using these new measurement techniques. Hopefully these trials will lead to ways to stop or reverse the progression of mesothelioma.
Mesothelioma Trial Phases
Clinical trials for evaluating mesothelioma treatments are broken into four parts or phases. These Phases are described below (Source FDA).
Phase I
Researchers evaluate a drug or treatment in a small group of people/patients (20 to 80) for the first time to evaluate a drug's safety, determine the appropriate dosage range and identify side effects.
Phase II
Researchers treat a larger group of people/patients to determine if the drug treatment is effective and safe for the dosage levels determined in Phase I.
Phase III
Researchers administer the drug or treatment to a large group of people/patients to confirm the effectiveness of the drug and evaluate the drug's side effects. In this phase, the drug under evaluation will be compared to commonly used treatments. Additionally, researchers use Phase III trials to determine the proper protocol for the use of the drug when it is released for routine treatment.
Phase IV
Researchers perform follow-up studies from Phase III, primarily to obtain information that can be used when marketing the drug, such as drug risks, benefits and optimum use.
Historically, cancer has been treated with drugs that inhibit the inner workings of cells. Many of these treatments, including chemotherapy medications, can have devastating side effects due to the fact that they also interrupt the processes of non-cancerous cells. Gene therapy research is aimed at developing treatments to overcome this obstacle by targeting the specific proteins that cause cells to mutate and become cancerous.
Mesothelioma occurs when a protein or set of proteins allow cells to grow in an uncontrolled manner. One such protein called mesothelin was found by researchers looking for differential expression of proteins between normal cells and mesothelioma cells. The increased presence of mesothelin on certain cells is thought to enable their growth and spread (metastasis), leading to cancers such as mesothelioma and pancreatic cancer. As a result, much of the mesothelioma research currently underway is focused on developing gene therapies or biopharmaceutical products that can directly block mesothelin function. In March 2009, biopharmaceutical company Morphotek announced the commencement of a Phase II clinical trial to evaluate MORAb-009 as a new therapeutic approach to treat mesothelioma. MORAb-009 is a monoclonal antibody — a replica of an antibody produced by the human body normally used to fight infectious disease.
Why MORAb-009?
MORAb-009 is a monoclonal antibody that tackles mesothelioma in two ways: by stimulating the body's immune system and by blocking the function of mesothelin. Monoclonal antibodies are a relatively new type of therapy cancer treatment. They are developed by identifying antibodies known to have a specific purpose and adapting them in the laboratory in such as way as to develop the exact characteristics needed to attack the proteins causing or involved in maintaining the disease.
Goals of the Clinical Trial
The MORAb-009 study is designed to provide patients with mesothelioma therapy that goes beyond the normal standard of care. Participants will receive a mesothelioma treatment consisting of MORAb-009 in combination with chemotherapy drugs Alimta (pemetrexed for injection) and cisplatin. The company's objectives are twofold: to assess the efficacy of MORAb-009 and to gain further evidence of its safety.
The company is hopeful that patients will be able to continue taking MORAb-009 for a matter of months, if not longer. While the scheduled treatment duration is one year, patients will have access to the treatment for as long as they respond to the therapy and need treatment. The entire clinical trial is scheduled to last approximately four years. After the first 33 patients enroll, the company along with expert independent oncologists will determine if their response was any better than would be expected for patients taking Alimta and cisplatin alone. If that is the case, an additional 45 patients will enroll in order to give the study statistical power to demonstrate efficacy.
Treatment Centers
Mesothelioma is a fatal form of cancer affecting the lining of body cavities; most frequently the chest (pleural mesothelioma), but the abdomen (peritoneal mesothelioma) and occasionally the heart (pericardial mesothelioma) are affected. At present time, the prognosis of mesothelioma patients is quite grim: 60 percent of patients die within one year of diagnosis. This is why studies such as the MORAb-009 clinical trial are so important. Patients diagnosed with mesothelioma should carefully weigh all options with their doctors to determine whether or not to participate in a clinical trial.
The treatment centers currently planning to participate in Morphotek's clinical trial are located in the U.S., Canada, Germany, Spain and the Netherlands, and additional treatment centers may be added. For the latest information on the MORAb-009 clinical trial and participating treatment centers, visit www.clinicaltrials.gov and type in: NCT00738582 or contact: 1-888-522-4743.
Editor’s Note: The clinical trials listed below are specific to mesothelioma and have participating centers in North America. The website of the National Cancer Institute lists additional mesothelioma trials being conducted abroad, as well as cancer clinical trials that include but are not specific to mesothelioma. For updated information on recruitment for any of the trials discussed in this article, visit clinicaltrials.gov.
Due to the ineffectiveness of single chemotherapy agents for the treatment of mesothelioma, most ongoing clinical trials now focus on evaluating combination treatments. Most of these trials attempt to assess the efficacy of drug therapies, although some involve surgery or other treatment combination modality combinations.
The following are typical strategies used by investigators when selecting combinations of drugs to test in clinical trials for the treatment of mesothelioma.
Different drug classes. Each drug in the combination must individually have at least some anti-tumor activity. Drugs belonging to different classes often have different mechanisms and are therefore more potent and more effective for combination treatment than drugs of the same class. For example, an alkylating agent, such as Platinol, in combination with an antimetabolite agent, such as Alimta, has a synergistic effect for fighting malignant mesothelioma. Using two types of alkylating agents would not be expected to have such a synergistic effect.
Different mechanisms. While using two types of the same agent may not be effective, when drugs within the same class function through different mechanisms, they may work well together. For example, antimetabolite drugs are designed to block the synthesis of DNA by impeding the nutrients and other chemicals needed for DNA metabolism. Two antimetabolite drugs that block different kinds of nutrients may be able to work together in a synergistic manner.
Different toxicity levels. Drugs that have different levels of toxicity dosage may also be evaluated for combination therapy. Drug combinations that can be given intermittently allow time for the patient to recover from the short-term side effects of the treatment.
Active Clinical Trials Involving Combination Treatments
The following is a list of ongoing clinical trials involving combination chemotherapy and other types of “combination treatments” for mesothelioma. Click on the links below each trial for updated information on eligibility and recruitment status.
Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients with MPM
This mesothelioma clinical trial will assess the effectiveness of combination therapy involving Carboplatin, Bevacizumab (Avastin) and Pemetrexed (Alimta) in treating patients with malignant pleural mesothelioma (MPM). (Click here to learn more about eligibility and recruitment.)
Study of CBP501 + Pemetrexed + Cisplatin in Patients with Solid Tumors (Phase I) and Patients with Malignant Pleural Mesothelioma (Phase II)
This malignant pleural mesothelioma clinical trial will combine full doses of cisplatin and pemetrexed with escalating doses of CBP501. The study is open to patients with confirmed solid malignant mesothelioma that has spread (metastasized) or is unable to be removed through surgery. (Click here to learn more about eligibility and recruitment.)
Short Neoadjuvant Hemithoracic IMRT for MPM
Though radiation treatment reduces the recurrence of tumors in the area treated by more than 90 percent, most mesothelioma patients treated with radiation succumb to the disease anyway. Researchers have suggested this paradox may occur as a result of tumor cells contaminating adjacent areas during surgery. This study will attempt to determine the effectiveness of sterilizing these cells through short, intense doses of radiation to the chest prior to surgery. (Click here to learn more about eligibility and recruitment.)
Pleurectomy/Decortication with Intraoperative Intrathoracic/Intraperitoneal Heated Cisplatin with Sodium Thiosulfate
This mesothelioma trial will assess the viability of administering cisplatin as well as Alimta in patients undergoing surgery with heated cisplatin. (Click here to learn more about eligibility and recruitment.)
Cisplatin, Pemetrexed and Bevacizumab for Untreated Malignant Mesothelioma
This malignant mesothelioma clinical trial will attempt to determine the effect of a combination therapy on progression of mesothelioma. The therapy consists of cisplatin, pemetrexed and bevacizumab. (Click here to learn more about eligibility and recruitment.)
Study Using Chemotherapy Followed by Intensity Modulated Radiation Therapy to the Pleura in Patients with Locally Advanced But Unresectable Malignant Pleural Mesothelioma
For certain types of mesothelioma, radiation therapy is typically not used due to the risk of severe side effects, including lung damage (pneumonitis). A new radiation technique known as intensity-modulated radiation therapy (IMRT) has shown promise in reducing these side effects. This clinical trial will assess the safety of using chemotherapy followed by IMRT. (Click here to learn more about eligibility and recruitment.)
An Efficacy Study of MORAb-009 in Subjects With Pleural Mesothelioma
This malignant pleural mesothelioma clinical trial will attempt to determine whether combination therapy involving cisplatin and pemetrexed is more effective when administered along with an experimental drug called MORAb-009. (Click here to learn more about eligibility and recruitment.)
Eloxatin® Plus Gemcitabine Chemotherapy for Mesothelioma
This clinical trial will test the response rate of patients treated with chemotherapy involving Oxaliplatin (ELOXATIN) and Gemcitabine. (Click here to learn more about eligibility and recruitment.)
Trimodal Lung-Sparing Treatment of Pleural Mesothelioma
Current treatments for pleural mesothelioma often lead to reduced lung function, ultimately requiring removal of the lung, which can dramatically affect lung function and quality of life. This clinical trial will attempt to show that measures can be taken to prevent the necessity of lung removal. (Click here to learn more about eligibility and recruitment.)
Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation Therapy for Mesothelioma
Investigators in this clinical trial will change the order in which the treatments that make up trimodality therapy (surgery, chemotherapy and radiation) are administered. They believe that treating patients with chemotherapy first, followed by surgery and radiation therapy, may reduce the recurrence of tumors and increase survival times. (Click here to learn more about eligibility and recruitment.)
Decitabine and FR901228 in Treating Patients with Advanced Lung Cancer, Esophageal Cancer, Pleural Mesothelioma, or Lung Metastases
Different chemotherapy drugs attack tumor cells differently; as a result, treatment that involves two different types of chemotherapy drugs may destroy more tumor cells. Investigators in this trial, which focuses on patients with inoperable pleural mesothelioma and other types of cancer, will attempt to determine the best doses of two types of chemotherapy drugs: FR901228 and decitabine. (Click here to learn more about eligibility and recruitment.)
Cisplatin, Pemetrexed, and Imatinib Mesylate in Malignant Mesothelioma
The primary objective of this malignant mesothelioma clinical trial is to determine the maximum tolerable dose of a combination drug therapy comprised of cisplatin, pemetrexed and imatinib mesylate. These drugs attack mesothelioma using three different mechanisms. (Click here to learn more about eligibility and recruitment.)
Immunotoxin Therapy, Pemetrexed, and Cisplatin in Treating Patients with Malignant Pleural Mesothelioma that Cannot Be Removed by Surgery
This mesothelioma clinical trial will study the best dosage and the side effects of a mesothelioma combination treatment consisting of two chemotherapy drugs (cisplatin and pemetrexed) plus immunotoxin therapy, in combination with one another. Each component of the therapy attacks cancer cells in a different manner. (Click here to learn more about eligibility and recruitment.)
Phase I Dose-Escalation Study of Azacitidine in Combination with Temozolomide
This “dose-escalation” clinical trial will attempt to assess the safety and toxicity of a combination drug therapy (Temozolomide and Azacititine) used to treat mesothelioma and advanced soft tissue sarcoma. (Click here to learn more about eligibility and recruitment.)
Extrapleural Pneumonectomy /Pleurectomy Decortication, IHOC Cisplatin and Gemcitabine with Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma
Following removal of pleural mesothelioma tumors, chemotherapy is used to kill tumor cells and stop them from dividing. This malignant pleural mesothelioma clinical trial will attempt to determine the safety of adding gemcitabine to the chemotherapy treatment. In addition, two “cytoprotection agents” will be used in an attempt to counter any potential side effects. (Click here to learn more about eligibility and recruitment.)
