Clinical Trials Logo

Clinical Trial Details — Status: Suspended

Administrative data

NCT number NCT03075527
Other study ID # 16-549
Secondary ID
Status Suspended
Phase Phase 2
First received
Last updated
Start date April 10, 2017
Est. completion date September 30, 2024

Study information

Verified date January 2024
Source Dana-Farber Cancer Institute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This research study is studying a pair of immunotherapies as a possible treatment for malignant pleural mesothelioma. The drugs involved in this study are: - Durvalumab - Tremelimumab


Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The FDA (the U.S. Food and Drug Administration) has not approved durvalumab or tremelimumab as a treatment for any disease. In this research study, the investigators are studying if the study drug can help your cancer compared to the usual approach to treating malignant pleural mesothelioma . Durvalumab is a drug that blocks a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cells. Tremelimumab blocks a receptor on immune cells that normally suppresses immune attack. These two study drugs have been used alone for mesothelioma but the combination has not yet been tested for mesothelioma. These two drugs have been used for cancers such as melanoma and have been effective than using either drug alone.


Recruitment information / eligibility

Status Suspended
Enrollment 19
Est. completion date September 30, 2024
Est. primary completion date June 7, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Written informed consent obtained prior to any study-specific procedures not considered part of routine medical care - Histologically or cytologically confirmed unresectable or medically inoperable malignant pleural mesothelioma - Disease progression after treatment with at least one line of chemotherapy that included a first-line platinum agent in combination with an anti-folate - Participants must have measurable disease according to modified RECIST for pleural malignant mesothelioma. (Bone metastases are not considered measurable.) Prior radiation to the only site of measurable disease will make the participant ineligible unless the lesion has been demonstrated to grow after completion of radiation therapy. - Participants must be willing and able to undergo a biopsy at the start of this study and an on-treatment biopsy if safe and feasible. - Participants must have be at least 28 days from any major surgery. - ECOG performance status of 0 or 1. - Subjects must have adequate hematologic, renal, and organ and marrow function - Age 18 years or older - Female subjects of childbearing potential who are sexually active with a non sterilized male partner must agree to use at least one highly effective method of contraception from the time of screening and must agree to continue using such precautions for 180 days after the last dose of investigational product. Male partners of a female subject must also agree to use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female patients should refrain from breastfeeding throughout this period. - Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or post-menopausal (defined as greater than or equal to 12 months with no menses without an alternative medical cause) - Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use male condom plus spermicide from screening through 180 days after the last dose of investigational product. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male patients should refrain from sperm donation throughout this period. Female partners of a male subject must use a highly effective method of contraception throughout this period. - Ability to understand and the willingness to sign a written informed consent document - Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up Exclusion Criteria: - Previous treatment with an immune check-point inhibitors, CTLA-4, PD-1, or PD-L1, including prior treatment with either durvalumab or tremelimumab - Known central nervous system metastasis. Patients with known brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease may be enrolled if they have been treated, are no longer taking corticosteroids, and have been stable on imaging for at least 3 weeks - Subjects currently receiving systemic corticosteroids above 10 mg per day for more than 14 days; subjects receiving other systemic immunosuppressive drugs for more than 14 days. Exceptions include: inhaled, intranasal, ophthalmic, and topical corticosteroids, local corticosteroid injections (e.g., intra-articular injections), and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan premedication) - Subjects with medical conditions that require the chronic use of systemic corticosteroids. Exceptions include: inhaled, intranasal, ophthalmic, and topical corticosteroids, local corticosteroid injections (e.g., intra-articular injections), and subjects requiring corticosteroid pre-medication for hypersensitivity reactions (e.g. CT scan premedication) - Active or prior documented autoimmune disease within the past 2 years, including but not limited to systemic lupus erythematosus, sarcoidosis syndrome, or Wegener's granulomatosis. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years are not excluded. - Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, celiac disease, diverticulitis), or any other chronic, serious gastrointestinal condition associated with diarrhea. NOTE: Subjects with known diverticulosis are permitted to enroll. - History of interstitial lung disease or pneumonitis that has required steroid administration. - History of primary immunodeficiency - History of allogeneic organ transplant - History of hypersensitivity to tremelimumab, durvalumab, or any excipient - Known history of active tuberculosis - Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab or tremelimumab - Participants with a history of a second primary malignancy. Exceptions include: patients with a history of malignancies that were treated curatively and have not recurred within 5 years prior to study entry; resected basal and squamous cell carcinomas of the skin, and completely resected carcinoma in situ of any type. - Participants who have had chemotherapy, biologic therapy, or investigational therapy within 21 days (including bevacizumab) or radiotherapy within 7 days prior to entering the study or those who have not recovered from adverse events due to agents administered - Any history of a prior immune-related adverse event (irAE) at least or greater than grade 3 while receiving any previous immunotherapy agent. - Participants who are receiving any other investigational agents. - Uncontrolled intercurrent illness including, but not limited to: - Ongoing or active infection - Gastritis - Symptomatic congestive heart failure - Severe hypertension (defined as BP at least or greater than160/100 during the screening period despite optimal medical management) - Unstable angina pectoris - Cardiac arrhythmia - Active bleeding diatheses - Active peptic ulcer disease - Psychiatric illness/social situations that would limit compliance with study requirements - Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction - Known past or present medical history HIV-positive - Subjects with known acute or chronic hepatitis B or hepatitis C. - Pregnant women are excluded from this study because tremelimumab and durvalumab have unknown effects on the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tremelimumab or durvalumab, breastfeeding women are also excluded. Female subjects of child bearing potential must have a negative serum pregnancy test obtained prior to trial registration. - Subjects who are involved in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). - Subjects who have undergone a pneumonectomy due to known potential for pulmonary toxicities and heightened risk for complications.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Tremelimumab
Tremelimumab blocks a receptor on immune cells that normally suppresses immune attack.
Durvalumab
Durvalumab is a drug that blocks a protein often produced by cancer cells or surrounding cells to suppress immune cells from attacking cancer cells.

Locations

Country Name City State
United States Dana Farber Cancer Institute Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Dana-Farber Cancer Institute AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. ORR was assessed every 8 weeks from Cycle 1 Day 1 until date of documented disease progression or death.
Secondary Overall Survival defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. Overall survival is assessed from date of registration until date of death on-treatment or during follow-up.
Secondary Progression Free Survival Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. PFS is measured from time of registration to date of radiographic progression per RECIST1.1 or death.
Secondary Duration of Response Time from documentation of tumor response to disease progression Duration of response will be assessed at study completion, after all participants are off treatment.
Secondary Adverse Events Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. Toxicity is assessed from the time of first dose of study medication until the participant comes off study. Adverse event profile will be assessed at study completion.
See also
  Status Clinical Trial Phase
Recruiting NCT01950572 - Tissue Procurement and Natural History Study of Patients With Malignant Mesothelioma
Terminated NCT01624090 - Mithramycin for Lung, Esophagus, and Other Chest Cancers Phase 2
Active, not recruiting NCT04242199 - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors Phase 1
Recruiting NCT05415098 - Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas Phase 1
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Recruiting NCT06057935 - A Study of Additional Chemotherapy After Surgery for People With Malignant Peritoneal Mesothelioma Phase 2
Terminated NCT02838745 - Study of Cytoreductive Surgery and Hyperthermic Intraoperative Chemotherapy With Pemetrexed and Cisplatin for MPM Phase 1
Terminated NCT02628535 - Safety Study of MGD009 in B7-H3-expressing Tumors Phase 1
Recruiting NCT01912547 - Thromboelastography During Surgery for Malignant Pleural Mesothelioma Phase 0
Completed NCT01521325 - A Single-Dose Pilot Study of Radiolabeled Amatuximab (MORAb-009) in Mesothelin Over Expressing Cancers Phase 1
Recruiting NCT02073500 - Peritoneal Surface Malignancies - Characterization, Models and Treatment Strategies
Recruiting NCT00996385 - Velcade and Eloxatin for Patients With Malignant Pleural or Peritoneal Mesothelioma Phase 2
Completed NCT02467426 - Isolated Thoracic Perfusion (ITP-F) for MPM Phase 2
Completed NCT00407459 - Phase II Study of Bevacizumab, Pemetrexed and Carboplatin as First-Line Therapy in Malignant Pleural Mesothelioma Phase 2
Completed NCT00787410 - An Open-label, Phase II Trial of ZD1839 (IRESSA) in Patients With Malignant Mesothelioma Phase 2
Terminated NCT01907100 - Nintedanib (BIBF 1120) in Mesothelioma Phase 2/Phase 3
Completed NCT04056026 - A Single Dose FMT Infusion as an Adjunct to Keytruda for Metastatic Mesothelioma Early Phase 1
Completed NCT02903914 - Arginase Inhibitor INCB001158 as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors Phase 1/Phase 2
Terminated NCT03319537 - Pevonedistat Alone and in Combination With Chemotherapy in Patients With Mesothelioma Phase 1/Phase 2
Terminated NCT03685591 - PF-06952229 Treatment in Adult Patients With Advanced Solid Tumors Phase 1