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Durvalumab in Combination With Tremelimumab in Subjects With Advanced Rare Solid Tumors

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ClinicalTrials.gov Identifier: NCT02938793
Recruitment Status : Recruiting
First Posted : October 19, 2016
Last Update Posted : May 23, 2019
Sponsor:
Collaborators:
AstraZeneca
MedImmune LLC
Information provided by (Responsible Party):
Prisma Health-Upstate

Brief Summary:
This is an investigator initiated single institution, open-label study to evaluate the antitumor activity, safety, and tolerability of durvalumab in combination with tremelimumab in subjects with select advanced rare solid tumors.

Condition or disease Intervention/treatment Phase
Cancer Rare Disease Drug: Durvalumab Drug: Tremelimumab Phase 2

Detailed Description:

This is an investigator initiated single institution, open-label study to evaluate the antitumor activity, safety, and tolerability of durvalumab in combination with tremelimumab in subjects with select advanced rare solid tumors. The dose-exploration phase, conducted across a range of tumor types, has been completed. The dose-expansion phase is ongoing and includes certain soft tissue sarcomas, neuroendocrine tumors and thymic carcinoma. Therefore, subjects diagnosed with any of those rare tumors are excluded from this trial. Given the safety and tolerability data in the previous and ongoing studies (Study D4190C00010 and D4190C00006), the selected dose for evaluation in all subjects enrolled in this trial is as follows:

Durvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) intravenously for 13 doses and Tremelimumab 75 mg Q4W (equivalent to 1 mg/kg Q4W) intravenously for 7 doses then every 12 weeks for 2 doses. Weight-based dosing should be utilized for patients <30 kg: durvalumab 20 mg/kg and tremelimumab 1 mg/kg. Tremelimumab will be administered first and the infusion duration will be approximately 1 hour. The durvalumab infusion will start approximately 1 hour after the end of the tremelimumab infusion and the infusion will be administered over approximately 1 hour.

The project Surveillance of Rare Cancers in Europe (RARECARE) collected data on cancers from 89 population-based cancer registries in 21 European countries, making it possible to study the epidemiology of these cancers as a whole in a large and heterogeneous population. Working from this database and the literature, a RARECARE working group produced a new list of cancers and developed a new definition of rare cancers (incidence < 6/100,000/year). This definition and working list are adopted for this rare tumor immunotherapy study.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Durvalumab (MEDI4736) (Anti-PD-L1 Antibody) in Combination With Tremelimumab (Anti-CTLA-4 Antibody) in Subjects With Advanced Rare Solid Tumors
Actual Study Start Date : December 1, 2016
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Single Arm
Durvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) intravenously for 13 doses and Tremelimumab 75 mg Q4W (equivalent to 1 mg/kg Q4W) intravenously for 7 doses then every 12 weeks for 2 doses.
Drug: Durvalumab
intravenous administration
Other Name: MEDI4736

Drug: Tremelimumab
intravenous administration
Other Name: CP-675,206




Primary Outcome Measures :
  1. Antitumor Activity [ Time Frame: 24 months ]
    To evaluate the antitumor activity of durvalumab in combination with tremelimumab based on immune-related Response Evaluation Criteria

  2. Incidence of Treatment-Emergent and Non Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 24 months ]
    To assess the safety and tolerability of durvalumab in combination with tremelimumab


Secondary Outcome Measures :
  1. Expression of programmed cell death protein 1 (PD-1) [ Time Frame: 24 months ]
    To evaluate the pharmacodynamic activity of durvalumab in combination with tremelimumab in the tumor microenvironment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of a rare advanced solid malignancy meeting EORTC criteria.
  • Subjects must have failed or been ineligible to receive standard treatment options if available.
  • Subjects must be amenable to biopsy of a tumor site or have recent (< 2 years) archival material available.
  • ECOG performance status of 0 to 2.
  • Life expectancy > 3 months.
  • Adequate normal organ and marrow function including: hemoglobin > 9.0 g/dl; ANC > 1500 per mm3; platelet count > 100,000 per mm3; bilirubin < 1.5 x ULN; ALT/AST < 2.5 x ULN unless liver metastases present in which case must be < 5 x ULN; creatinine clearance > 40 ml/min by Cockcroft-Gault or 24 hour urine collection

Exclusion Criteria:

  • Previous treatment with durvalumab or tremelimumab.
  • Prior treatment with any checkpoint inhibitor (including anti-CTLA-4, anti-PD-1 and anti-PD-L1).
  • Rare malignancies under investigation in other studies including thymic carcinoma, certain sarcomas, and neuroendocrine tumors.
  • Untreated central nervous system metastatic disease.
  • Active or documented autoimmune disease within previous 2 years.
  • Uncontrolled psoriasis.
  • Prior chemotherapy within 28 days of the first dose of durvalumab or tremelimumab.
  • Steroid exposure within 28 days of the first dose of durvalumab or tremelimumab with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02938793


Contacts
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Contact: Julie C Martin, DNP 864-455-3600 ext 3667 julie.martin@prismahealth.org
Contact: Jan Kueber, RN, BSN 864-455-3600 ext 3774 jan.kueber@prismahealth.org

Locations
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United States, South Carolina
Greenville Health System Cancer Institute Recruiting
Greenville, South Carolina, United States, 29605
Contact: Fiona Davidson, RN, BSN    864-455-3600 ext 3737    fiona.davidson@prismahealth.org   
Contact: Lisa M Johnson, RN, BSN    8644553600 ext 3735    lisa.johnson@prismahealth.org   
Principal Investigator: W. Jeff Edenfield, MD         
Sub-Investigator: Ki Y Chung, MD         
Sponsors and Collaborators
Prisma Health-Upstate
AstraZeneca
MedImmune LLC
Investigators
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Principal Investigator: William J Edenfield, MD Prisma Health-Upstate

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Responsible Party: Prisma Health-Upstate
ClinicalTrials.gov Identifier: NCT02938793     History of Changes
Other Study ID Numbers: ESR-15-11633
First Posted: October 19, 2016    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: aggregate data only

Keywords provided by Prisma Health-Upstate:
cancer, malignancy

Additional relevant MeSH terms:
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Rare Diseases
Disease Attributes
Pathologic Processes
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs