Clinical Trials Involving Combination Treatments

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 combination treatment modalities.

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.

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.)

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.)

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.)

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.)

Phase I/II Randomized Study of Pemetrexed Disodium and Cisplatin With Versus Without Cediranib Maleate in Patients With Malignant Pleural Mesothelioma

The drug cediranib maleate is sometimes used in combination with cisplatin and pemetrexed disodium to treat malignant mesothelioma. This study seeks, among other objectives, to establish how much of these drugs should be administered in phase II, as well as the maximum dose of this combination drug therapy. It also seeks to compare the survival rate with different combinations of these drugs, as well as their safety and toxicity. (Click here to learn more about eligibility and recruitment.)

Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas

Certain types of cancers have antigens (protein molecules) on their surfaces. Research has shown that administering a vaccine containing these antigens sometimes causes a beneficial immune response. The purpose of this clinical trial is to assess, in patients with cancers of the chest such as mesothelioma, the safety and effectiveness of vaccines used to attack tumor cells when combined with the cancer drugs cyclophosphamide and delecoxib. (Click here to learn more about eligibility and recruitment.)

Phase II Randomized Study of Pemetrexed Disodium Maintenance Therapy Versus Observation in Patients With Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy

This study will attempt to establish whether observation or maintenance therapy with pemexetred improve progression-free survival time of patients suffering from pleural mesothelioma whose disease is stable or better following first-line treatment with a combination of pemetrexed disodium and either carboplatin and cisplatin. The study also seeks to determine the toxicity of this regimen. (Click here to learn more about eligibility and recruitment.)

Randomized Study of Adjuvant WT-1 Analog Peptide Vaccine in Patients With Malignant Pleural Mesothelioma (MPM) After Completion of Combined Modality Therapy

This clinical trial will attempt to determine if mesothelioma is delayed or prevented from growing back after administration of a Wilms Tumor-1 (WT1) vaccine. WTI is a protein found in cancer cells. It causes cells to grow and regulates gene expression. (Click here to learn more about eligibility and recruitment.)

Sunitinib and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors That Have Not Responded to Chemotherapy

Researchers believe sunitinib may halt the growth of tumor cells by obstructing enzymes involved in cell growth, and by obstructing the flow of blood to the tumor. Administering sunitinib along with hydroxychloroquine could increase the number of tumor cells killed. This trial will attempt to determine the correct dosage of sunitinib with hydroxychloroquine, as well as the side effects of this regimen in patients with advanced tumors that have not responded well to chemotherapy. (Click here to learn more about eligibility and recruitment.)

Radical Pleurectomy/Decortication (PD) and Intensity Modulated Radiotherapy (IMRT)

This clinical research study will attempt to identify the highest dose of radiation that can be administered directly to the outer lining of the lungs (the pleura). The study will involve patients with malignant mesothelioma who have undergone pleurectomy and will be conducted using intensity modulated radiation therapy (IMRT). (Click here to learn more about eligibility and recruitment.)

Tumor Cell Vaccines With ISCOMATRIX(Trademark) Adjuvant and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers and Malignant Pleural Mesotheliomas

Research has demonstrated that triggering an immune response to tumor cells may slow or halt tumor growth. One method of doing this is to collect and alter tumor cells in a lab and then reintroduce these cells to the patient in the form of a vaccine; this encourages an immune response. In this clinical trial, researchers will attempt to add an experimental drug called ISCOMATRIX to such a vaccine in order to determine if doing so might trigger a stronger response. They will also assess the efficacy of administering celecoxib (an anti-inflammatory drug) with the vaccine. (Click here to learn more about eligibility and recruitment.)

SS1P and Pentostatin Plus Cyclophosphamide for Mesothelioma

This study will assess the effectiveness of administering a cancer drug called SS1P in combination with cyclophosphamide and pentostatin. SS1P is designed to attack a protein called mesothelin, which is found in certain types of cancer cells, including mesothelioma cells. Cyclophosphamide and pentostatin inhibit the immune system and it is thought that they may render SS1P more effective. (Click here to learn more about eligibility and recruitment.)

SS1(dsFV)PE38 Plus Pemetrexed and Cisplatin to Treat Malignant Pleural Mesothelioma

A combination therapy consisting of the drugs cisplatin and pemetrexed is often administered to patients with malignant mesothelioma. However, this treatment’s effects are limited. Researchers hope that adding a genetically engineered drug called SS1(dsFV)PE38 will help. SS1(dsFV)PE38 contains an antibody that attaches to a protein found on mesothelioma cells, as well as a toxin stemming from the bacterium Pseudomonas aeruginosa. The researchers hope that the antibody will attach itself to the mesothelioma cancer cells and allow the toxin to enter and destroy the cells. (Click here to learn more about eligibility and recruitment.)

Combination Gene Transfer and Chemotherapy

This clinical trial will attempt to assess the safety of a combination therapy consisting of chemotherapy and gene therapy when administered to patients with pleural mesothelioma. First a catheter will be placed and then the patients will receive two doses of interapleural vector. This will be followed by four to six cycles of frontline or second line chemotherapy every 21 days. (Click here to learn more about eligibility and recruitment.)

Early Palliative Care With Standard Oncology Care Versus Standard Oncology Care Alone in Advanced Lung and Non-colorectal Gastrointestinal Malignancies

In this study researchers hope to determine whether patients and families of patients with mesothelioma or certain other cancers have a better experience with standard oncology care or the same care combined with palliative care that begins shortly after diagnosis. Participants will be given questionnaires to help the researchers assess factors such as mood, coping, understanding of the illness, and quality of life. (Click here to learn more about eligibility and recruitment.)

See Also:

» Treatments Under Investigation

[Page updated January 2012]