Clinical Trials /

An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.

NCT03084471

Description:

To evaluate the safety, tolerability, and anti-tumor activity of the combination of durvalumab + tremelimumab or durvalumab alone in different solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.
  • Official Title: An Open-Label, Multi-Centre, Safety Study of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.

Clinical Trial IDs

  • ORG STUDY ID: D4191C00068
  • NCT ID: NCT03084471

Conditions

  • Advanced Solid Malignancies

Interventions

DrugSynonymsArms
MEDI4736 (Durvalumab)Combination therapy
MEDI4736 (Durvalumab) + TremelimumabCombination therapy

Purpose

To evaluate the safety, tolerability, and anti-tumor activity of the combination of durvalumab + tremelimumab or durvalumab alone in different solid tumors.

Detailed Description

      This is an open-label, multi-center, study to determine the short and long term safety of
      fixed doses of durvalumab 1500 mg + tremelimumab 75 mg combination therapy or durvalumab 1500
      mg monotherapy in patients with advanced solid malignancies. This study is modular in design,
      one or more of the modules will be opened in a given country / region based on local patient
      population prevalence, and results of feasibility studies. The total number of patients to be
      enrolled overall and in each module will depend on the types and number of tumor modules
      added to the main study and country-specific ancillary studies. The number of patients and
      sites to be involved in individual countries will be dependent on each module or ancillary
      study. This study consisted of a screening period, a treatment period, a 90 day safety
      follow-up period and a survival follow-up period. Patients will receive the investigation
      product (IP) via intravenous (IV) infusion once every 4 weeks (Q4W) in combination therapy or
      monotherapy as mentioned below - Combination therapy: Durvalumab 1,500 mg + tremelimumab 75
      mg on Week 0, for up to a maximum of 4 doses (or cycles) followed by durvalumab 1,500 mg
      starting 4 weeks after the last infusion of the combination or discontinuation of
      tremelimumab.

      Monotherapy: Durvalumab 1,500 mg on week 0.

      Patients will attend a safety follow-up visit 90 days after study treatment discontinuation.
      Thereafter, patients will be contacted by phone or electronic communication every 3 months
      for survival status up to 5 years following date of first patient treatment initiation. All
      patients will be followed for a minimum of 6 months following enrolment of last patient. It
      is anticipated that the total enrolment period for the overall study will be approximately 2
      to 3 years, with an overall duration of approximately 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Combination therapyExperimentalCombination therapy (durvalumab + tremelimumab) : Patients will receive the combination therapy followed by monotherapy via intravenous (IV) infusion once Q4W: Durvalumab 1,500 mg + tremelimumab 75 mg on Week 0, for up to a maximum of 4 doses (or cycles) and Durvalumab 1,500 mg starting 4 weeks after the last infusion of the combination or discontinuation of tremelimumab.
  • MEDI4736 (Durvalumab)
  • MEDI4736 (Durvalumab) + Tremelimumab
MonotherapyExperimentalMonotherapy (Durvalumab 1,500 mg): Patients will receive durvalumab 1,500 mg via IV infusion Q4W on Week 0.
  • MEDI4736 (Durvalumab)

Eligibility Criteria

        Inclusion Criteria:

          1. Must have a life expectancy of at least 12 weeks.

          2. Age ≥ 18 years at the time of screening. For patients aged <20 years and enrolled in
             Japan, a written informed consent should be obtained from the patient and his or her
             legally acceptable representative

          3. Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol. Written informed consent and any locally required authorization (e.g.,
             Health Insurance Portability and Accountability Act in the US, European Union [EU]
             Data Privacy Directive in the EU) obtained from the patient/legal representative prior
             to performing any protocol-related procedures, including screening evaluations.

          4. Disease not amendable to curative surgery

          5. Eastern Cooperative Oncology Group (ECOG) performance status as defined in the
             specific module.

          6. Body weight >30 kg.

          7. No prior exposure to anti-programmed death (PD) 1 or anti-PD-ligand (L) 1.

          8. Adequate organ and marrow function.

          9. Female patients of childbearing potential (i.e., not surgically sterile or
             post-menopausal) who are sexually active with a non-sterilized male partner must 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
             durvalumab + tremelimumab combination therapy or 90 days after the last dose of
             durvalumab monotherapy.

         10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women <50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               -  Women ≥50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

         11. Non-sterilized male patients who are sexually active with a female partner of
             childbearing potential must use a male condom plus spermicide from screening through
             180 days after receipt of the final dose of durvalumab + tremelimumab combination
             therapy or 90 days after receipt of the final dose of durvalumab monotherapy.

        For inclusion in the Module A of the study patients should fulfill the following criteria:

          1. Histologically or cytologicaly confirmed locally advanced or metastatic urothelial or
             non-urothelial carcinoma of the urinary tract (including the urinary bladder, ureter,
             urethra and renal pelvis)

          2. Disease that has progressed during or after at least one previous platinum or
             nonplatinum based chemotherapy, either for metastatic disease or progressive disease
             less than 12 months after adjuvant or neo-adjuvant chemotherapy

          3. ECOG performance status 0-2

        Exclusion Criteria:

          1. Involvement in the planning and/or conduct of the study.

          2. Previous IP assignment in the present study.

          3. Concurrent enrollment in another clinical study or another sub-study of this protocol,
             unless it is an observational (non-interventional) clinical study or during the
             follow-up period of an interventional study.

          4. Participation in another clinical study with an IP and receipt of any investigational
             anticancer therapy during the last / within 28 days or 5 half-lives, whichever is
             shorter, prior to the first dose of study treatment.

          5. Any concurrent chemotherapy, investigational agent, biologic, or hormonal therapy for
             cancer treatment.

          6. Local treatment of isolated lesions for palliative intent is acceptable (e.g., local
             surgery or radiotherapy).

          7. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
             radiation within 4 weeks of the first dose of study drug.

          8. Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of IP.

          9. History of allogenic organ transplantation.

         10. Uncontrolled intercurrent illness (ongoing or active infection, symptomatic congestive
             heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
             arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions
             associated with diarrhea, or psychiatric illness/social situations that would limit
             compliance with study requirement, substantially increase risk of incurring AEs or
             compromise the ability of the patient to give written informed consent.

         11. History of another primary malignancy, leptomeningeal carcinomatosis and active
             primary immunodeficiency.

         12. Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
             identified either on baseline brain imaging (please refer to RECIST for details on the
             imaging modality) obtained during the screening period or identified prior to signing
             the ICF. Brain metastases will not be recorded as RECIST Target Lesions at baseline.

         13. Active infection including tuberculosis, hepatitis B virus, hepatitis C virus, or
             human immunodeficiency virus (positive HIV ½ antibodies).

        14. Current or prior use of immunosuppressive medication within 14 days before the first
        dose of durvalumab or tremelimumab.

        15. Active or prior documented autoimmune or inflammatory disorders (including inflammatory
        bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of
        diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome
        [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis,
        uveitis, etc]).

        16) Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.

        17) Known allergy or hypersensitivity to study drug(s) or compounds of similar biologic
        composition to the study drug(s), or any of the study drug excipients.

        18) Any unresolved NCI CTCAE Grade ≥2 toxicities from prior anti-cancer therapy with the
        exception of vitiligo, alopecia, and the laboratory values defined in the inclusion
        criteria.

        19) Pregnant or breastfeeding women or male or female patients of reproductive potential
        who are not willing to employ effective birth control from screening to 180 days after the
        last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose
        of durvalumab monotherapy.

        20) Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical
        study regardless of treatment arm assignment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Number of patients with adverse events of special interest (AESIs).
Time Frame:From screening to safety follow up visit (90 days after last dose).
Safety Issue:
Description:To assess the AESIs as a criteria of safety and tolerability variables.

Secondary Outcome Measures

Measure:Safety: Number of patients with treatment-emergent adverse events (TEAEs).
Time Frame:From screening to safety follow up visit (90 days after last dose).
Safety Issue:
Description:To assess the incidence, severity, nature, seriousness, intervention/treatment, outcome, and causality of TEAEs (including serious adverse events [SAEs])
Measure:Safety: Number of patients who discontinued treatment due to TEAEs (including SAEs).
Time Frame:From screening to safety follow up visit (90 days after last dose).
Safety Issue:
Description:To assess the incidence and frequency of durvalumab ± tremelimumab discontinuation due to TEAEs (including SAEs)
Measure:Safety: Number of patients who had treatment interrupted due to TEAEs (including SAEs).
Time Frame:From screening to safety follow up visit (90 days after last dose).
Safety Issue:
Description:To assess the incidence and frequency of durvalumab ± tremelimumab interruption due to TEAEs (including SAEs).
Measure:Efficacy: Overall survival (OS) rate
Time Frame:Up to 5 years following date of first patient treatment initiation.
Safety Issue:
Description:Overall survival was defined as the time from the first date of treatment until death due to any cause. To assess OS of durvalumab + tremelimumab combination therapy or durvalumab monotherapy.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Programmed death ligand 1 (PD-L1)
  • Cytotoxic T-lymphocyte antigen-4 (CTLA-4)
  • Durvalumab in combination with tremelimumab

Last Updated