Clinical Trials /

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

NCT02938793

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab in Combination With Tremelimumab in Subjects With Advanced Rare Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: ESR-15-11633
  • NCT ID: NCT02938793

Conditions

  • Cancer
  • Rare Disease

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Single Arm
TremelimumabCP-675,206Single Arm

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalDurvalumab, 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.
  • Durvalumab
  • Tremelimumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Antitumor Activity
Time Frame:24 months
Safety Issue:
Description:To evaluate the antitumor activity of durvalumab in combination with tremelimumab based on immune-related Response Evaluation Criteria

Secondary Outcome Measures

Measure:Expression of programmed cell death protein 1 (PD-1)
Time Frame:24 months
Safety Issue:
Description:To evaluate the pharmacodynamic activity of durvalumab in combination with tremelimumab in the tumor microenvironment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Prisma Health-Upstate

Trial Keywords

  • cancer, malignancy

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