Clinical Trials /

A Study of Anti-PD1 (Nivolumab) Therapy as Pre- and Post-operative Therapy in Metastatic Renal Cell Cancer (ADAPTeR)

NCT02446860

Description:

Single arm, open label, phase II trial. Participants to undergo biopsy of primary tumour followed by 8 weeks of nivolumab therapy followed by nephrectomy. Nivolumab to be continued post-operatively

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Anti-PD1 (Nivolumab) Therapy as Pre- and Post-operative Therapy in Metastatic Renal Cell Cancer (ADAPTeR)
  • Official Title: A Study of Anti-PD1 (Nivolumab) Therapy as Pre- and Post-operative Therapy in Metastatic Renal Cell Cancer (ADAPTeR)

Clinical Trial IDs

  • ORG STUDY ID: CCR 4151
  • NCT ID: NCT02446860

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
nivolumabOpdivoNivolumab

Purpose

Single arm, open label, phase II trial. Participants to undergo biopsy of primary tumour followed by 8 weeks of nivolumab therapy followed by nephrectomy. Nivolumab to be continued post-operatively

Detailed Description

      Renal cell carcinoma (RCC) is diagnosed in around 8500 patients annually in the UK.
      Approximately one third of these patients present with metastatic disease where the RCC has
      spread to other organs. The mainstay of treatment for these patients is systemic drug
      therapy, but surgery to remove the primary kidney tumour (i.e. nephrectomy) may also provide
      clinical benefit.

      There is no standard preoperative systemic drug therapy in metastatic RCC, but such
      preoperative therapy is used widely in the treatment of other cancer types. This approach has
      several potential advantages including shrinking the tumour to help improve surgical outcomes
      and to aid identification of appropriate postoperative Drug therapy.

      Over the last 10 years several agents have demonstrated promising activity in RCC including
      the monoclonal antibody therapy nivolumab. This novel immunotherapy works by blocking an
      immune cell receptor (programmed death1(PD1)) which the cancer can otherwise utilise to evade
      an individuals immune system attack. This study will investigate the use of nivolumab therapy
      as a preoperative treatment in patients with metastatic RCC for whom nephrectomy is planned.
      A total of 19 patients will be recruited at the Royal Marsden Hospital Patients will be
      treated with nivolumab for 8 weeks prior to surgery, after which nivolumab therapy will
      restart and continue until such time that the patient is not receiving an overall clinical
      benefit.

      The primary aim of the study will be to assess the safety of such a strategy, with further
      aims to assess clinical effectiveness. This is also a unique opportunity to further
      investigate the way in which nivolumab works and to identify predictors of treatment
      response. To achieve this patients will be asked to provide biopsy samples of their RCC pre &
      post nivolumab treatment and their nephrectomy tissue for research use, alongside additional
      blood & urine samples.
    

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimentalNivolumab 3 mg/kg by intravenous infusion, given every two weeks for eight weeks prior to nephrectomy, then post-operatively until patient is no longer deriving clinical benefit
  • nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically confirmed metastatic renal cell carcinoma of predominately clear cell
             type

          2. At least one site of disease outside the kidney measurable per RECIST 1.1

          3. Scheduled to undergo nephrectomy as part of treatment plan

          4. No prior systemic therapy for renal cell carcinoma

          5. Male or female, 18 years of age or older

          6. Life expectancy of 12 weeks or greater

          7. ECOG performance status 0 or 1

          8. Immunosuppressive doses of systemic medications, such as steroids or absorbed topical
             steroids (equivalent to 10 mg of prednisone daily or more) must be discontinued at
             least two weeks prior to administration of the study drug. Inhaled corticosteroids and
             adrenal replacement steroid doses of > 10 mg daily prednisone equivalent are permitted
             in the absence of active autoimmune disease.

          9. Serum aspartate transaminase (AST) / serum alanine transaminase (ALT) ≤3x upper limit
             of normal (ULN)

         10. Total serum bilirubin ≤1.5 x ULN (except subjects with Gilbert syndrome, who can have
             total bilirubin <3mg/dL (50µmol/L)

         11. Serum creatinine ≤1.5 x ULN or creatinine clearance ≥40ml/min (measured or calculated
             using Cockcroft-Gault formula)

         12. White blood cells (WBC) ≥ 2.0x109/L, Absolute neutrophil count (ANC) ≥1.5x109/L

         13. Platelets ≥100 x109/L,

         14. Haemoglobin ≥9.0 g/dL

         15. Prothrombin time (PT) ≤1.5 x ULN

         16. Signed and dated informed consent document indicating that the patient (or legally
             acceptable representative) has been informed of all pertinent aspects of the trial
             prior to enrollment

         17. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures

        Exclusion Criteria:

          1. Intracranial disease, unless there has been radiological evidence of stable
             intracranial disease > 6 months.

          2. Need for nephrectomy to relieve symptoms relating to the primary tumour or for
             emergency nephrectomy

          3. History of severe hypersensitivity reaction to other monoclonal antibodies

          4. Prior malignancy, active within the last 3 years, except for locally curable cancers
             which have been apparently cured

          5. Known HIV or AIDS-related illness

          6. Any active, known or suspected autoimmune disease or any condition requiring systemic
             treatment with either corticosteroids or other immunosuppressive medications within 14
             days of study drug administration. Inhaled or topical steroids and physiological
             replacement doses >10mg daily prednisolone equivalent are permitted in the absence of
             active autoimmune disease.

          7. Active infection requiring therapy

          8. Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA)
             indicating acute or chronic infection

          9. Pregnancy or breastfeeding. Female patients must be surgically sterile or be
             postmenopausal, or must agree to use effective contraception during the period of
             therapy and for 26 weeks following the last dose of study drug. All female patients
             with childbearing potential must have a negative pregnancy test (serum or urine) prior
             to enrolment/nivolumab treatment. Male patients must be surgically sterile or must
             agree to use effective contraception during the period of therapy and for 31 weeks
             after the last dose of study drug. Women who are not of childbearing potential and
             azoospermic men do not require contraception.

         10. Current signs or symptoms of severe progressive or uncontrolled hepatic, haematologic,
             gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related
             to RCC

         11. Use of vaccines against infectious diseases (eg influenza, varicella) within 28 days
             of initiation of study therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety profile of Nivolumab given pre- and post-nephrectomy in metastatic renal cell carcinoma. Safety will be assessed by a summary of adverse events and by the proportion of patients experiencing all grades of toxicity.
Time Frame:Until disease progression, measured every 2 weeks, on average for 11 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Response rate
Time Frame:Until progression or withdrawal of consent, measured every 8 weeks in first year and then every 12 weeks there after, on average for 11 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Royal Marsden NHS Foundation Trust

Last Updated

March 23, 2018