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

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

Condition: Renal Cell Carcinoma

Intervention:

  • Drug: nivolumab

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

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02446860

Sponsor: Royal Marsden NHS Foundation Trust

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:

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:

Estimated Enrollment: 19

Study Start Date: April 2015

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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) ≥ 2.0×109/L, Absolute neutrophil count (ANC) ≥1.5×109/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

Contact:

  • Lyra Del Rosario
  • 02078082710

Location:

  • The Royal Marsden NHS Foundation Trust
  • London SW36JJ United Kingdom

View trial on ClinicalTrials.gov

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