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

NCT02446860 | Terminated Phase 2 DMC

• 1 other identifier: CCR 4151
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Until disease progression, measured every 2 weeks, on average for 11 months

Secondary Outcomes (1)

• Response rate

  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

Other Outcomes (3)

• Progression free survival

  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

• Overall survival

  Until death or withdrawal of consent, measured every 12 weeks, on average for 12 months

• Changes in biomarkers

  Until progression or withdrawal of consent, at cycle 1, pre-nephrectomy and at disease progression, on average for 11 months

Study Arms (1)

Nivolumab

EXPERIMENTAL

Nivolumab 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

Drug: nivolumab

Interventions

nivolumab DRUG

Nivolumab 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.

Also known as: Opdivo

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic renal cell carcinoma of predominately clear cell type
• At least one site of disease outside the kidney measurable per RECIST 1.1
• Scheduled to undergo nephrectomy as part of treatment plan
• No prior systemic therapy for renal cell carcinoma
• Male or female, 18 years of age or older
• Life expectancy of 12 weeks or greater
• ECOG performance status 0 or 1
• 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.
• Serum aspartate transaminase (AST) / serum alanine transaminase (ALT) ≤3x upper limit of normal (ULN)
• Total serum bilirubin ≤1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin \<3mg/dL (50µmol/L)
• Serum creatinine ≤1.5 x ULN or creatinine clearance ≥40ml/min (measured or calculated using Cockcroft-Gault formula)
• White blood cells (WBC) ≥ 2.0x109/L, Absolute neutrophil count (ANC) ≥1.5x109/L
• Platelets ≥100 x109/L,
• Haemoglobin ≥9.0 g/dL
• Prothrombin time (PT) ≤1.5 x ULN

You may not qualify if:

• Intracranial disease, unless there has been radiological evidence of stable intracranial disease \> 6 months.
• Need for nephrectomy to relieve symptoms relating to the primary tumour or for emergency nephrectomy
• History of severe hypersensitivity reaction to other monoclonal antibodies
• Prior malignancy, active within the last 3 years, except for locally curable cancers which have been apparently cured
• Known HIV or AIDS-related illness
• 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.
• Active infection requiring therapy
• Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA) indicating acute or chronic infection
• 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.
• Current signs or symptoms of severe progressive or uncontrolled hepatic, haematologic, gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related to RCC
• Use of vaccines against infectious diseases (eg influenza, varicella) within 28 days of initiation of study therapy

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead

Study Sites (1)

The Royal Marsden NHS Foundation Trust

London, SW36JJ, United Kingdom

Location

Related Publications (1)

• Au L, Hatipoglu E, Robert de Massy M, Litchfield K, Beattie G, Rowan A, Schnidrig D, Thompson R, Byrne F, Horswell S, Fotiadis N, Hazell S, Nicol D, Shepherd STC, Fendler A, Mason R, Del Rosario L, Edmonds K, Lingard K, Sarker S, Mangwende M, Carlyle E, Attig J, Joshi K, Uddin I, Becker PD, Sunderland MW, Akarca A, Puccio I, Yang WW, Lund T, Dhillon K, Vasquez MD, Ghorani E, Xu H, Spencer C, Lopez JI, Green A, Mahadeva U, Borg E, Mitchison M, Moore DA, Proctor I, Falzon M, Pickering L, Furness AJS, Reading JL, Salgado R, Marafioti T, Jamal-Hanjani M; PEACE Consortium; Kassiotis G, Chain B, Larkin J, Swanton C, Quezada SA, Turajlic S; TRACERx Renal Consortium. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma. Cancer Cell. 2021 Nov 8;39(11):1497-1518.e11. doi: 10.1016/j.ccell.2021.10.001. Epub 2021 Oct 28.

  PMID: 34715028 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• James Larkin

  Royal Marsden NHS Foundation Trust

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2015
• First Posted: May 18, 2015
• Study Start: April 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)