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

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ClinicalTrials.gov Identifier: NCT03297593
Recruitment Status : Recruiting
First Posted : September 29, 2017
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

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.


Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: nivolumab Drug: ipilimumab Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective single-stage single-arm multicenter phase II trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab in Combination With Ipilimumab in Patients With Metastatic Renal Cell Carcinoma: A Multicenter Single-arm Phase lI Trial
Actual Study Start Date : December 13, 2017
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : December 1, 2037

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: nivolumab and ipilimumab

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
240 mg every 2 weeks during the first 20 weeks, 480 mg every 4 weeks thereafter
Other Name: Opdivo

Drug: ipilimumab
After 2 weeks 1mg/kg every 6 weeks
Other Name: Yervoy




Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: at 2 years. ]

    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.



Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: at weeks 8, 14, 20, 26, and then every 12 weeks up to 2 years. ]

    PFS is defined as the time from registration until progression according to RECIST v1.1 or death from any cause, 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.

    Patients without event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment showing non-progression (before the start of the new therapy, if any).


  2. Duration of response (DOR) [ Time Frame: at weeks 8, 14, 20, 26, and then every 12 weeks up to 2 years. ]

    DOR is defined as time from the date when a patient first meets the criteria for PR or CR according to RECIST v1.1, until documented progression, relapse or death due to disease progression, 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.

    Patients without event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment showing non-progression before the start of the new therapy (if any).

    DOR will only be analyzed in the subgroup of patients achieving PR or CR during trial treatment.


  3. Time to treatment failure [ Time Frame: at weeks 8, 14, 20, 26, and then every 12 weeks up to 2 years. ]
    Time to treatment failure, defined as time from registration to treatment discontinuation due to any reason. Patients still on treatment at the time of analysis will be censored at the date of last treatment administration. 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.

  4. Overall survival (OS) [ Time Frame: At weeks 8. 14, 20, 26, then every 12 weeks until 2 years. ]
    OS is defined as the time from registration until death from any cause. Patients without event at the time of analysis will be censored at the date they were last known to be alive.

  5. Adverse events (AEs) [ Time Frame: at weeks 8, 14, 20, 26, then every 12 weeks, until 100 days after last dose of treatment. ]
    AEs are assessed according to NCI CTCAE v4.03.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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, 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
  • Women with child-bearing potential are using effective contraception are not pregnant or lactating and agree not to become pregnant during trial treatment and during 5 months thereafter. A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential.
  • Men agree not to father a child during trial treatment and during 5 months thereafter

Exclusion Criteria:

  • 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)
  • Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03297593


Contacts
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Contact: Catherine Berset, MD +41 31 389 91 91 trials@sakk.ch

Locations
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Switzerland
Kantonsspital Aarau Recruiting
Aarau, Switzerland, 5001
Contact: Deborah Zihler, MD    +41 62 838 97 99    deborah.zihler@ksa.ch   
Principal Investigator: Deborah Zihler, MD         
Kantonsspital Baden Recruiting
Baden, Switzerland, 5404
Contact: Andreas Erdmann, MD    +41 56 486 27 62    andreas.erdmann@ksb.ch   
Principal Investigator: Andreas Erdmann, MD         
Universitätsspital Basel Recruiting
Basel, Switzerland, 4031
Contact: Frank Stenner, Prof    +41 61 265 50 74    frank.stenner@usb.ch   
Principal Investigator: Frank Stenner, Prof         
Inselspital Bern Recruiting
Bern, Switzerland, 3030
Contact: Julian Schardt, MD    +41 31 632 11 55    julian.schardt@insel.ch   
Principal Investigator: Julian Schardt, MD         
Kantonsspital Baselland Bruderholz Recruiting
Bruderholz, Switzerland, 4101
Contact: Lorenz Jost, MD    +41 61 436 21 85    lorenz.jost@ksbh.ch   
Principal Investigator: Lorenz Jost, MD         
Kantonsspital Graubünden Recruiting
Chur, Switzerland, 7000
Contact: Richard Cathomas, MD    +41 81 256 66 95    richard.cathomas@ksgr.ch   
Principal Investigator: Richard Cathomas, MD         
Spital Thurgau Recruiting
Frauenfeld, Switzerland, 8500
Contact: Regina Woelky, MD    +41 52 723 76 91    regina.woelky@stgag.ch   
Principal Investigator: Regina Woelky, MD         
HFR - Hôpital cantonal Recruiting
Fribourg, Switzerland, 1708
Contact: Marc Küng, MD    +41 26 306 22 60    Marc.Kueng@h-fr.ch   
Principal Investigator: Marc Küng, MD         
Hôpitaux Universitaires de Genève Recruiting
Genève, Switzerland, 1221
Contact: Nicolas Mach, Prof    +41 22 372 98 81    Nicolas.Mach@hcuge.ch   
Principal Investigator: Nicolas Mach, Prof         
Centre hospitalier universitaire vaudois - CHUV Recruiting
Lausanne, Switzerland, 1011
Contact: Dominik Berthold, MD    +41 21 314 80 83    dominik.berthold@chuv.ch   
Principal Investigator: Dominik Berthold, MD         
Luzerner Kantonsspital Recruiting
Luzern, Switzerland, 6000
Contact: Christian Riklin, MD    +41 41 205 58 73    christian.riklin@luks.ch   
Principal Investigator: Christian Riklin, MD         
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Christian Rothermund, MD    +41 71 494 11 63    christian.rothermundt@kssg.ch   
Principal Investigator: Christian Rothermund, MD         
Kantonsspital Winterthur Recruiting
Winterthur, Switzerland, 8401
Contact: Miklos Pless, Prof    +41 52 266 36 40    miklos.pless@ksw.ch   
Principal Investigator: Miklos Pless, Prof         
UniversitätsSpital Zürich Recruiting
Zürich, Switzerland, 8091
Contact: Axel Mischo, MD    +41 44 255 22 14    axel.mischo@usz.ch   
Principal Investigator: Axel Mischo, MD         
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
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Study Chair: Frank Stenner, Prof Universitätsspital Basel
Study Chair: Heinz Läubli, MD Universitätsspital Basel

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Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT03297593     History of Changes
Other Study ID Numbers: SAKK 07/17
First Posted: September 29, 2017    Key Record Dates
Last Update Posted: October 18, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Swiss Group for Clinical Cancer Research:
renal cell carcinoma
Nivolumab
Ipilimumab
metastatic renal cell carcinoma
immunotherapy
Opdivo
Yervoy
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents