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A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC

NCT03963414

Description:

This Phase I, multicenter, study is designed to evaluate the safety and tolerability of durvalumab (anti-programmed death-ligand 1 [PD-L1] antibody) and tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody) in combination with intravenous (IV) carboplatin plus (+) etoposide in treatment naïve patients with extensive-stage small cell lung cancer (ES-SCLC) and performance status 2 (PS2). Eighteen patients with untreated ES-SCLC and PS2 will be enrolled. Cohort 1, which includes the first 6 subjects, will receive IV carboplatin and etoposide Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression. If 2 out of 6 patients have dose-limiting toxicities, then the study will be closed. Cohort 2, which will include 12 additional subjects, will receive chemotherapy Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV + tremelimumab 75 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4, then durvalumab 1500 mg + tremelimumab 75 mg will be administered Q 3 weeks during cycles 5 and 6. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
  • Official Title: A Phase I Study of Durvalumab (MEDI4736) Plus Tremelimumab in Combination With Platinum-based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer and Performance Status 2

Clinical Trial IDs

  • ORG STUDY ID: 275-19
  • NCT ID: NCT03963414

Conditions

  • Small Cell Lung Carcinoma

Purpose

This Phase I, multicenter, study is designed to evaluate the safety and tolerability of durvalumab (anti-programmed death-ligand 1 [PD-L1] antibody) and tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody) in combination with intravenous (IV) carboplatin plus (+) etoposide in treatment naïve patients with extensive-stage small cell lung cancer (ES-SCLC) and performance status 2 (PS2). Eighteen patients with untreated ES-SCLC and PS2 will be enrolled. Cohort 1, which includes the first 6 subjects, will receive IV carboplatin and etoposide Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression. If 2 out of 6 patients have dose-limiting toxicities, then the study will be closed. Cohort 2, which will include 12 additional subjects, will receive chemotherapy Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV + tremelimumab 75 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4, then durvalumab 1500 mg + tremelimumab 75 mg will be administered Q 3 weeks during cycles 5 and 6. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalDurvalumab 1500 mg via IV infusion every 3 weeks, starting on Week 7, for up to a maximum of 2 doses/cycles followed by durvalumab maintenance monotherapy 1500 mg via IV infusion every 4 weeks, starting 4 weeks after Cycle 4.
    Cohort 2ExperimentalDurvalumab 1500 mg plus tremelimumab 75 mg via IV infusion every 3 weeks, starting on Week 7, for up to a maximum of 2 doses/cycles followed by durvalumab monotherapy 1500 mg via IV infusion every 4 weeks, starting 4 weeks after the last infusion of the combination.

      Eligibility Criteria

              Inclusion Criteria:
      
                1. Age ≥ 18 years old at time of study entry (consent) and adult male or female (For
                   Nebraska, ≥19 years old)
      
                2. Histologically or cytologically confirmed ES-SCLC
      
                3. Tumor biopsy or cytology should be obtained within 8 weeks of initiation of treatment.
      
                4. Brain metastases; must be asymptomatic or treated and stable, off steroids for at
                   least 1 month prior to study treatment.
      
                5. Have not received any prior therapy for SCLC, except palliative radiation. If the
                   patient received radiation, there must be measurable disease outside the radiation
                   field.
      
                6. Measurable disease or evaluable disease based on RECIST Version 1.1.
      
                7. Eastern Cooperative Oncology Group ECOG = 2
      
                8. Body weight > 30 kg
      
                9. No active secondary malignancy. Patients with other prior malignancies will be
                   included, provided they have been disease-free for at least five years.
      
               10. Adequate hematologic and end organ function
      
               11. Women of childbearing potential must have a pregnancy test (urine or serum) proven
                   negative within 14 days prior to registration.
      
              Exclusion Criteria:
      
                1. Participation in another clinical study with an investigational product during the
                   last 28 days.
      
                2. Any previous chemotherapy and /or immunotherapy for SCLC
      
                3. Current or prior use (≤ 14 days before first doses of study drugs) of
                   immunosuppressive medication.
      
                4. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
      
                5. History of another primary malignancy except for malignancy treated with curative
                   intent and with no known active disease ≥5 years before the first dose of IP
      
                6. History of leptomeningeal carcinomatosis
      
                7. Paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic steroids or
                   clinical symptomatology suggesting worsening of PNS
      
                8. Active infection including tuberculosis, HIV, hepatitis B and C.
      
                9. Active or prior documented autoimmune or inflammatory disorders
      
               10. Uncontrolled cardiovascular disease
      
               11. History of active primary immunodeficiency
      
               12. Pregnant or lactating women
      
               13. Known allergies, hypersensitivity, or intolerance to any of the study medications,
                   excipients, or similar compounds.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Incidence of Treatment-related Adverse Events with a Severity of 3 or higher (Safety and tolerability)
      Time Frame:3 months
      Safety Issue:
      Description:Evaluate the safety and tolerability profile of durvalumab + tremelimumab in combination with carboplatin and etoposide in ES-SCLC and PS2. Adverse events with a severity grade of 3 or higher per CTCAE guidelines will be used to assess this outcome.

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:Vinicius Ernani

      Trial Keywords

      • Extensive stage small cell lung cancer

      Last Updated