Nivolumab in Combination With Ipilimumab in Patients With Metastatic Renal Cell Carcinoma

NCT03297593 | Completed Phase 2 DMC

• 1 other identifier: SAKK 07/17
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 14

Brief Summary

Immunotherapy with checkpoint inhibitors that target PD-1 and CTLA-4 have shown activity in mRCC. However, the optimal schedule of the combination therapy has yet to be defined. The objective of the trial is to determine the efficacy of combination immunotherapy of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma. The expansion phase shall address the role of ipilimumab in case of clinically insignificant progression.

Conditions

Renal Cell Carcinoma

Keywords

renal cell carcinoma; Nivolumab; Ipilimumab; metastatic renal cell carcinoma; immunotherapy; Opdivo; Yervoy

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  ORR is defined as proportion of patients achieving partial response (PR) or complete response (CR) according to RECIST v1.1 at any time between registration and documented disease progression\*, death, or subsequent therapy, whichever occurs first. \*PD before the 3rd administration of ipilimumab not leading to treatment discontinuation does not count as progression for this endpoint. Furthermore, the additional tumor assessment at 20 weeks for patients with PD n.c.s. before week 20 will not be taken into consideration for calculation of this endpoint.

  at 2 years.

Secondary Outcomes (5)

• Progression-free survival (PFS)

  at weeks 8, 14, 20, 26, and then every 12 weeks up to 2 years.

• Duration of response (DOR)

  at weeks 8, 14, 20, 26, and then every 12 weeks up to 2 years.

• Time to treatment failure (TTF)

  at weeks 8, 14, 20, 26, and then every 12 weeks up to 2 years.

• Overall survival (OS)

  At weeks 8. 14, 20, 26, then every 12 weeks until 2 years.

• Adverse events (AEs)

  at weeks 8, 14, 20, 26, then every 12 weeks, until 100 days after last dose of treatment.

Study Arms (1)

nivolumab and ipilimumab

EXPERIMENTAL

Patients start treatment with nivolumab (240 mg every 2 weeks during the first 20 weeks, 480 mg every 4 weeks thereafter). After 2 weeks, ipilimumab (1mg/kg every 6 weeks) will be introduced. As soon as a radiographic complete response (CR) or partial response (PR) is observed, ipilimumab has to be stopped and only the single-agent treatment with nivolumab is continued. Once ipilumimab has been stopped because of a response, it will not be re-started later on.

Drug: nivolumab; Drug: ipilimumab

Interventions

nivolumab DRUG

240 mg every 2 weeks during the first 20 weeks, 480 mg every 4 weeks thereafter

Also known as: Opdivo

nivolumab and ipilimumab

ipilimumab DRUG

After 2 weeks 1mg/kg every 6 weeks

Also known as: Yervoy

nivolumab and ipilimumab

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 according to Swiss law and ICH/GCP regulations before registration and prior to any trial specific procedures
• Histologically or cytologically confirmed, locally advanced and/or metastatic clear cell RCC not amenable to surgery or definitive radiotherapy, and requiring systemic therapy
• Patient able and willing to provide serial biopsies and blood drawings (initial, at 14 weeks (except for patient in the expansion cohort), and at progression).
• Measurable disease
• In case of second line patients, the previous therapy must be stopped at least 2 weeks prior to registration
• Age ≥ 18 years
• WHO performance status of 0-1
• Bone marrow function: neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L
• Hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST, ALT and AP ≤ 2.5 x ULN (≤ 5 x ULN if significant hepatic metastasis is suspected to be the cause for enzyme elevation)
• Renal function: eGFR \> 20 mL/min/1.732
• Cardiac function: NYHA ≤ 2. In case of cardiac insufficiency NYHA 1 or 2, Left ventricular Ejection Fraction (LVEF) ≥ 35% as determined by echocardiography (ECHO) or multigated acquisition (MUGA) scan
• Men agree not to father a child during trial treatment and during 5 months thereafter

You may not qualify if:

• Uncontrolled CNS metastases. Patients with asymptomatic CNS metastases (at least 2 weeks after radiotherapy or surgery and steroids with prednisone equivalent of 10 mg or lower) are eligible
• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration with the exception of pT1-2 prostate cancer Gleason score \< 6, adequately treated cervical carcinoma in situ, or localized non-melanoma skin cancer.
• More than one previous line of systemic therapy for mRCC
• Prior immunotherapy.
• Concurrent or recent (within 30 days of registration) treatment with any other experimental drug
• Concomitant use of other anti-cancer drugs or radiotherapy except for local pain control (radiotherapy of target lesion not allowed)
• Immunosuppressive medications (such as but not limited to: methotrexate, azathioprine, and TNF-α blockers) within 30 days before registration
• Exception:
• systemic corticosteroids at doses not exceeding 10 mg/day of prednisone or equivalent
• immunosuppressive medications for patients with contrast allergies
• inhaled and intranasal corticosteroids
• Live attenuated vaccination within 30 days prior to registration and for 30 days after last dose of any of the trial drugs. Inactivated viruses, such as those in the influenza vaccine, are permitted
• History of or active auto-immune disease with the exception of diabetes mellitus type II
• Human immunodeficiency virus (HIV) infection or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment
• Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (14)

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Inselspital Bern

Bern, 3030, Switzerland

Location

Kantonsspital Baselland Bruderholz

Bruderholz, 4101, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Spital Thurgau

Frauenfeld, 8500, Switzerland

Location

HFR - Hôpital cantonal

Fribourg, 1708, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, 1221, Switzerland

Location

Centre hospitalier universitaire vaudois - CHUV

Lausanne, 1011, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Nivolumab; Ipilimumab

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

• Frank Stenner, Prof

  Universitätsspital Basel

  STUDY CHAIR

• Heinz Läubli, MD

  Universitätsspital Basel

  STUDY CHAIR

Study Design

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

Model Details: Prospective single-stage single-arm multicenter phase II trial.

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 29, 2017
• Study Start: December 13, 2017
• Primary Completion: July 1, 2019
• Study Completion: April 30, 2025
• Last Updated: June 6, 2025

Record last verified: 2025-06

Locations

CH (14)