Purpose: The aim of this study is to identify biomarkers of disease recurrence and prognosis to optimize patient selection for treatment with cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), and through animal models to explore different treatment strategies for peritoneal surface malignancies (PSM).
Peritoneal Mesothelioma
αDC1 Vaccine + Chemokine Modulatory Regimen (CKM) as Adjuvant Treatment of Peritoneal Surface Malignancies
Purpose:
This trial is to determine the safest dose of a triple combination (chemokine modulatory regimen or CKM) of celecoxib, interferon alfa (IFN), and rintatolimod that can be given with a DC vaccine as treatment of peritoneal surface malignancies after standard of care surgery.
The first phase of this study will determine the safest dose of IFN that can be given in combination with celecoxib and rintatolimod along with a DC vaccine. The doses of celecoxib (400 mg) and rintatolimod (200 mg) will be consistent while the dose of IFN will be increased (5, 10, or 20 MU/m2) as participants are enrolled to the trial. The high dose of IFN in combination with celecoxib and rintatolimod will be used for the next phase of the clinical trial. After surgery, participants will receive 2 cycles of the investigational treatment.
The second phase of this study will test if the investigational treatment has any effects on peritoneal surface malignancies. The doses of the combination determined in the first phase will be used in this phase of the clinical trial. After surgery, participants will receive 2 cycles of the investigational treatment, followed by standard chemotherapy as determined by their oncologist, and then 2 more cycles of the investigational treatment.
A Dose Escalation Study to Assess Safety of GSK2256098 (FAK Inhibitor) in Combination With Trametinib (MEK Inhibitor) in Subjects With Advanced Solid Tumors
Purpose: The purpose of this study is to assess the safety of combination treatment of GSK2256098 and trametinib in mesothelioma subjects and subjects with other selected tumor types. Also, the study will identify a maximum tolerated combination dose of GSK2256098 and trametinib. This study is a Phase I, open-label, dose-escalation study to determine maximal tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) and regimens for oral MEK inhibitor trametinib (once daily [OD]dosing) and the oral FAK inhibitor GSK2256098 (twice daily [BID] dosing). The synergy of the combination was observed over a wide range of concentrations and results in several-fold reduction in compound concentration to achieve equivalent biological responses compared to either single agent. The dose and schedule of dosing may be modified based on emerging safety, pharmacokinetic (PK), and pharmacodynamic (PD) data. The study will be conducted in two parts; Part 1 Dose Escalation to determine the MTD and RP2D and Part 2 Expansion Cohort to further evaluate the safety and tolerability of trametinib and GSK2256098 at the RP2D and determine clinical activity. Additionally, in Part 1 Dose Escalation, additional subjects with malignant pleural mesothelioma (MPM) will be recruited at doses that are considered tolerable in order to assess PD in MPM subjects at each dose (the Pharmacodynamic Cohort). The Expansion Cohort will be limited to subjects with MPM who have progressed or are intolerant to first-line therapy.
- Arm: Experimental: Part 1
- Part 1 will determine the MTD and RP2D based on the safety and tolerability of GSK2256098 administered with trametinib. Subject will be administered starting dose of 1.0 mg OD trametinib combined with 500 mg BID GSK2256098. Dose escalation will continue until the MTD is established.
- Assigned Interventions
- Drug: GSK2256098
GSK2256098 250 mg will be supplied as white to off-white, round, biconvex tablets with no markings. GSK2256098 will be administered 30 minutes after a light meal with approximately 240 milliliter of water.
- Drug: Trametinib
Trametinib 0.5 mg will be supplied as capsules with no identifying markings. Trametinib will be administered orally under fasting conditions two hours after a meal.
- Arm: Experimental: Part 2
- Based on determination of combination dose regimen in Part 1, dose expansion cohorts for Part 2 will be opened.
- Assigned Interventions
- Drug: GSK2256098
GSK2256098 250 mg will be supplied as white to off-white, round, biconvex tablets with no markings. GSK2256098 will be administered 30 minutes after a light meal with approximately 240 milliliter of water.
- Drug: Trametinib
Trametinib 0.5 mg will be supplied as capsules with no identifying markings. Trametinib will be administered orally under fasting conditions two hours after a meal.
Tivantinib in Treating Patients With Previously Treated Malignant Mesothelioma
Purpose: This phase II trial studies how well tivantinib works in treating patients with previously treated malignant mesothelioma. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
- Arms
- Experimental: Treatment (tivantinib)
- Patients receive tivantinib PO BID. Treatment continues in the absence of disease progression or unacceptable toxicity.
- Assigned Interventions
- Drug: tivantinib
- Given PO
- Other Name: ARQ 197
- Other: laboratory biomarker analysis
- Correlative studies
Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Subjects With Unresectable Malignant Mesothelioma
Purpose: This is a Phase 2, randomized, double-blind, parallel-group study. Subjects with unresectable pleural or peritoneal malignant mesothelioma will be randomized in a 2:1 ratio to receive either tremelimumab or placebo. Approximately 180 subjects will be enrolled at study centers in multiple countries. The study consists of a screening period, a treatment period, and a 90-day follow-up period.
Arms and Assigned Interventions:
- Experimental: Tremelimumab
- Drug: Tremelimumab
- Tremelimumab is to be administered as an IV solution, followed by observation.
- Placebo Comparator: Placebo
- Drug: Placebo
- Placebo is to be administered as an IV solution, followed by observation.
Safety and Efficacy of Oshadi D and Oshadi R for Malignant Mesothelioma Treatment
Purpose: Malignant mesothelioma is a rare neoplasm that arises most commonly from the mesothelial surfaces of the pleural cavity, occasionally from the peritoneal surface, and rarely from the tunica vaginalis or pericardium. It has an extremely poor prognosis with a median survival of 4 to 13 months for untreated patients 1 and 6 to 18 months for treated patients, regardless of the therapeutic approach.
The anticancer activity of Oshadi D and Oshadi R treatment was tested in preclinical studies and in phase I clinical study. Four metastatic mesothelioma patients are treated for 5 to 12 months. The Oshadi D and Oshadi R combination treatment was generally well-tolerated with no dose-limiting toxicities observed.
Register With Patients in Which Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) Was Performed
Purpose: The purpose of this study is to register the follow-up data of patients who, because of a peritoneal surface malignancy, will undergo cytoreductive surgery and HIPEC.
- Registry
- Patients with peritoneal carcinomatosis of colorectal origin, patients with pseudomyxoma peritonei (type DPAM or PMCA) and patients with peritoneal mesothelioma who are planned to undergo cytoreductive surgery and HIPEC because of a peritoneal surface malignancy
Erlotinib Hydrochloride in Treating Patients With Malignant Peritoneal Mesothelioma
Purpose: The purpose of this study is to test the drug erlotinib (erlotinib hydrochloride) in people with malignant peritoneal mesothelioma who have a specific genetic mutation in their cancer. Erlotinib has been approved by the United States Food and Drug Administration (FDA) for other cancers, but erlotinib has not been approved for malignant peritoneal mesothelioma. This research is being done because there is no current standard treatment for malignant peritoneal mesothelioma and the study doctors want to see how erlotinib affects malignant peritoneal mesothelioma.
- Arms: Experimental: Treatment (enzyme inhibitor therapy)
- Patients receive erlotinib hydrochloride PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Drug: erlotinib hydrochloride
- Given PO
- Other Names:
- CP-358,774
- erlotinib
- OSI-774
- Other: laboratory biomarker analysis
- Correlative studies
BAY 94-9343 for Advanced Solid Tumors
Purpose:
- Background:
- Mesothelin is a protein on the lining of the lungs, heart, and abdomen. It is often present at higher levels on some cancer cells. Anticancer drugs given directly to cells with high mesothelin levels may help destroy the cancer cells with fewer effects on healthy cells. BAY 94-9343 combines an anticancer drug with a type of protein that targets mesothelin. Researchers want to see if BAY 94-9343 can treat advanced cancers that have mesothelin on the cells.
- Objectives:
- To test the safety and effectiveness of BAY 94-9343 on advanced solid tumors.
- Eligibility:
- Individuals at least 18 years of age who have advanced solid tumors that have mesothelin on the cells.
- Design:
-
- Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, and imaging studies. Heart and lung function tests and an eye exam will also be included.
- The study drug will be given in 3-week cycles of treatment. At the start of each cycle, participants will have BAY 94-9343 as an infusion for about 1 hour.
- Treatment will be monitored with frequent blood tests, heart and lung function tests, and imaging studies. Treatment will continue as long as the tumor does not start growing and no severe side effects develop.
Study of ABT-700 in Subjects With Advanced Solid Tumors
Purpose: This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-700 in subjects with advanced solid tumors. The early clinical development plan for ABT-700 is based on the activity demonstrated in preclinical models. Approximately 51 to 75 subjects will be enrolled.
- Arms
-
- Cohort A: Experimental
- ABT-700 will be administered by intravenous infusion at escalating dose levels in 21-day dosing cycles. Additional subjects will be enrolled in an expansion cohort that will further evaluate ABT-700.
- Intervention: Drug: ABT-700
- Cohort B: Experimental
- ABT-700 plus erlotinib 150 mg qd (21-day cycle).
- Intervention: Drug: ABT-700 plus erlotinib
- Cohort C: Experimental
- ABT-700 plus oxaliplatin and capecitabine. ABT-700 IV (Day 1) Oxaliplatin: 130 mg/m2 IV (Day 1) Capecitabine: 1000 mg/m2 Oral (twice daily Days 1 – 14).
- Intervention: Drug: ABT-700 plus Oxaliplatin and Capecitabine
- Cohort A: Experimental
