Study in Which Therapy is Either Switched to Nivolumab After 3 Months of Treatment or Therapy is Continued With a Tyrosine Kinase Inhibitor in Patients With Metastatic Renal Cell Carcinoma (RCC) and Disease Control

NCT02959554 | Terminated Phase 2

• 3 other identifiers: AIO-NZK-0116ass.CA209-4432016-002170-13
• Study Type: interventional
• Target: 49
• Locations: 2 countries
• Sites: 2

Brief Summary

This study aims to assess the survival benefit from an early switch approach from sunitinib or pazopanib (10-12 weeks of 1st-line therapy) to nivolumab (anti-angiogenic to immunotherapy switch).

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Advanced; Metastatic; RCC

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Efficacy measure

  128 of events in max. 72 months

Secondary Outcomes (5)

• Best overall response rate

  From start of 1st line until disease progression or death of last patient (max. 72 months)

• Progression free survival (PFS)

  72 months

• Quality of Life

  From randomization until disease progression or death of last patient (max. 72 months)

• Quality of Life

  From randomization until disease progression or death of last patient (max. 72 months)

• Safety - Absolute and relative frequencies of emergent adverse events according to CTCAE 4.03

  From randomization until 100 days after end of treatment of last patient (post last dose).

Study Arms (2)

Nivolumab (A)

EXPERIMENTAL

Nivolumab: 240 mg i.v. on D1 of every cycle (Q2W) for 16 weeks. After 16 weeks 480 mg i.v. on D1 of every cycle (Q4W) until disease progress, intolerable toxicity, withdrawal of consent or end of study.

Drug: Nivolumab

TKI (B)

ACTIVE COMPARATOR

Sunitinib: According to Standard of Care (SOC). Recommended dose is 50 mg p.o. once daily for 4 consecutive weeks followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks (until disease progress, intolerable toxicity, withdrawal of consent or end of study) or Pazopanib: According to Standard of Care (SOC). Recommended dose is 800 mg p.o. daily continuously (until disease progress, intolerable toxicity, withdrawal of consent or end of study)

Drug: Sunitinib; Drug: Pazopanib

Interventions

Nivolumab DRUG

240 mg i.v. on D1 of every cycle (Q2W) for 16 weeks. After 16 weeks 480 mg i.v. on D1 of every cycle (Q4W) until disease progress, intolerable toxicity, withdrawal of consent or end of study.

Also known as: Opdivo

Nivolumab (A)

Sunitinib DRUG

According to Standard of Care (SOC). Recommended dose is 50 mg p.o. once daily for 4 consecutive weeks followed by a 2-week rest period (schedule 4/2) to comprise a complete cycle of 6 weeks (until disease progress, intolerable toxicity, withdrawal of consent or end of study).

Also known as: Sutent

TKI (B)

Pazopanib DRUG

According to Standard of Care (SOC). Recommended dose is 800 mg p.o. daily continuously (until disease progress, intolerable toxicity, withdrawal of consent or end of study).

Also known as: Votrient

TKI (B)

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Age ≥ 18 years at time of study entry
• Eastern Co-operative Oncology Group (ECOG) performance status 0-2.
• Metastatic or locally advanced RCC with clear cell component, not amenable to surgery with curative intention.
• First-line treatment with a TKI for 10-12 weeks (limited to sunitinib or pazopanib).
• Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1). If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable lesion that has not been irradiated. Patients with bone lesions as the only measurable lesion are eligible, provided that lesions consist of soft tissue, which is assessed via CT or MRI.
• Documented partial response or stable disease to first-line TKI exposure at 10-12 weeks.

You may not qualify if:

• Adequate blood count, liver-enzymes, and renal function (obtained no later than 14 days prior to start of study treatment):
• White Blood Cells (WBC) ≥ 2000/μL
• Neutrophils ≥ 1500/μL
• Platelets ≥ 100 x10\^3/μL
• Hemoglobin \> 9.0 g/dL
• Serum creatinine ≤ 1.5 x Upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = ((140-age in years) x weight in kg x 0.85)/(72 x serum creatinine in mg/dL)
• Male CrCl=((140-age in years) x weight in kg x 1.00)/(72 x serum creatinine in mg/dL)
• Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) ≤ 3 x ULN
• Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of nivolumab.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic) men do not require contraception.
• Prior systemic therapy other than 10-12 weeks SOC TKI treatment for advanced or metastatic RCC.
• Standard of care 1st-line TKI treatment for advanced or metastatic RCC for longer than 12 weeks.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Medizinische Universität Wien - Universitätsklinik für Innere Medizin I, Klinische Abteilung für Onkologie

Vienna, 1090, Austria

Location

Universitätsklinikum Essen (AöR) - Klinik und Poliklinik für Urologie / Kinderurologie und Uroonkologie

Essen, 45147, Germany

Location

Related Publications (2)

• Grunwald V, Ivanyi P, Zschabitz S, Wirth M, Staib P, Schostak M, Dargatz P, Muller L, Metz M, Bergmann L, Steiner T, Welslau M, Lorch A, Rafiyan R, Hellmis E, Darr C, Schutt P, Meiler J, Kretz T, Loidl W, Florcken A, Manz M, Hinke A, Hartmann A, Grullich C. Nivolumab Switch Maintenance Therapy After Tyrosine Kinase Inhibitor Induction in Metastatic Renal Cell Carcinoma: A Randomized Clinical Trial by the Interdisciplinary Working Group on Renal Tumors of the German Cancer Society (NIVOSWITCH; AIO-NZK-0116ass). Eur Urol. 2023 Dec;84(6):571-578. doi: 10.1016/j.eururo.2023.09.004. Epub 2023 Sep 26.

  PMID: 37758574 DERIVED

• Hofmann F, Hwang EC, Lam TB, Bex A, Yuan Y, Marconi LS, Ljungberg B. Targeted therapy for metastatic renal cell carcinoma. Cochrane Database Syst Rev. 2020 Oct 14;10(10):CD012796. doi: 10.1002/14651858.CD012796.pub2.

  PMID: 33058158 DERIVED

Related Links

• Description: Working Group for Medical Oncology (AIO) within the German Cancer Society (DKG)

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

Nivolumab; Sunitinib; pazopanib

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Viktor Grünwald, Prof.Dr.

  Coordinating Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: November 9, 2016
• Study Start: December 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: January 1, 2021
• Last Updated: September 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); DE (1)