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Sunitinib Followed by Avelumab or the Reverse for Metastatic Renal Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT03035630
Recruitment Status : Withdrawn (Principal investigator left lead institution and efforts to open the protocol at another institution were not successful.)
First Posted : January 30, 2017
Last Update Posted : January 30, 2019
Sponsor:
Collaborators:
Hoosier Cancer Research Network
Pfizer
Information provided by (Responsible Party):
Guru Sonpavde, Hoosier Cancer Research Network

Brief Summary:
This is an open label, randomized phase II trial. Eligible subjects will be randomized in a 1:1 ratio and stratified for known prognostics variables to one of two first-line medication treatment arms. Once disease progression has been documented, and following a required inter-line washout period, subjects will receive either second-line medication treatment or discontinue treatment, per discretion of treating investigator.

Condition or disease Intervention/treatment Phase
Clear-cell Renal Cell Carcinoma RCC Kidney Cancer Clear-cell Kidney Carcinoma Drug: Avelumab Drug: Sunitinib Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Masking Description: Open-Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial Comparing Sequential First-line Sunitinib and Second-line Avelumab vs First-line Avelumab and Second-line Sunitinib for Metastatic Renal Cell Carcinoma: SUAVE Trial. Hoosier Cancer Research Network GU15-223
Actual Study Start Date : May 23, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Avelumab then Sunitinib for Investigational Arm A

First-Line Medication:

  • Avelumab 10mg/kg IV on D1 and D15 of every 28 day cycle, until irRECIST 1.1 disease progression criteria is documented.

    • Subjects will have a mandatory an inter-line washout period (14-60 days) before receiving first dose of second-line medication.

Second-Line Medication:

  • Sunitinib 50 mg po once daily from D1 to D14 of every 21 day cycle until RECIST 1.1 disease progression criteria is documented.

Subjects who do not have disease progression at end of first-line treatment and are removed due to toxicities or personal decision, may switch to either the second-line therapy or be monitored during the inter-line period until progression, which may be longer than 60 days.

Drug: Avelumab
Avelumab 10mg/kg IV over 60 minutes on D1 and D15 of every 28 day cycle
Other Name: MSB0010718C

Drug: Sunitinib
Sunitinib 50 mg once daily from D1 to D14 of every 21 day cycle
Other Name: Sutent

Experimental: Sunitinib then Avelumab for Investigational Arm B

First-Line Medication:

  • Sunitinib 50 mg po once daily from D1 to D14 of every 21 day cycle until RECIST 1.1 disease progression criteria is documented.

    • Subjects will have a mandatory inter-line washout period (14-60 days) before receiving first dose of second-line medication.

Second-Line Medication:

  • Avelumab 10mg/kg IV on D1 and D15 of every 28 day cycle, until irRECIST 1.1 disease progression criteria is documented.

Subjects who do not have disease progression at end of first-line treatment and are removed due to toxicities or personal decision, may switch to either the second-line therapy or be monitored during the inter-line period until progression, which may be longer than 60 days.

Drug: Avelumab
Avelumab 10mg/kg IV over 60 minutes on D1 and D15 of every 28 day cycle
Other Name: MSB0010718C

Drug: Sunitinib
Sunitinib 50 mg once daily from D1 to D14 of every 21 day cycle
Other Name: Sutent




Primary Outcome Measures :
  1. Overall Progression-Free Survival (PFS) [ Time Frame: up to 24 months ]
    Compare PFS1 + PFS2 rates for overall PFS


Secondary Outcome Measures :
  1. Overall Failure-Free Survival (FFS) [ Time Frame: up to 24 months ]
    Compare FFS1 rates for first-line therapy on each arm

  2. Overall Survival (OS) [ Time Frame: up to 36 months ]
    Compare OS rates for subjects on each arm

  3. Overall Response Rate (RR) [ Time Frame: 2 years ]
    Compare RR and PFS1 of sunitinib vs. avelumab as first-line therapy and PFS2 as second-line therapy

  4. Overall Toxicities [ Time Frame: up to 36 months ]
    Describe toxicities of sunitinib and avelumab



Information from the National Library of Medicine

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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:

Subjects must meet all of the following applicable inclusion criteria to participate in this study:

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration.
  • Age ≥ 18 years at the time of consent.
  • Karnofsky performance status ≥ 60 within 28 days prior to registration.
  • Histological or cytological confirmation of ccRCC (component of clear cell histology required).
  • Measurable metastatic disease according to RECIST 1.1 criteria within 28 days prior to registration.
  • Received no prior mTOR or PD1/PD-L1 inhibitors (prior IL-2 is allowed). Prior VEGF inhibitor is allowed only if >12 months prior to registration, and only if earlier if administered in the neoadjuvant or adjuvant setting
  • Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 60 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria:

Subjects meeting any of the criteria below may not participate in the study:

  • Active infection requiring systemic therapy.
  • Known HIV positive (HIV testing is not required for eligibility)
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Known additional invasive malignancy that is active and/or progressive requiring treatment; exceptions include locally curable cancers, or other cancer for which the subject has been disease-free for at least three years or prostate cancer on surveillance.
  • Active central nervous system (CNS) metastases (previously treated CNS metastasis are allowed if subject completed radiation ≥2 weeks earlier and off steroids, and neurologically stable or subject has been on requiring ≤10 mg of daily prednisone or prednisone equivalent dose of another corticosteroid for ≥2 weeks) is acceptable)
  • Treatment with any investigational agent (chemotherapy or biologic treatment) within 28 days prior to registration.
  • Subjects who have not recovered from toxicities from prior systemic anti-cancer treatment or local therapies (a residual toxicity likely to be chronic but controlled and manageable is allowed, e.g. endocrine syndromes from prior interleukin-2).
  • Subjects who have undergone major surgery < 4 weeks or minor surgery < 2 weeks prior to registration. Wounds must be completely healed prior to study entry and subjects must have recovered from all toxicities from surgery. NOTE: placement of a vascular access device is not considered major or minor surgery in this regard.
  • Prior radiation therapy is allowed as long as irradiated area was not the sole source of measurable disease and radiotherapy was completed with recovery from toxicity, at least 2 weeks prior to registration, and subject has recovered from toxicity. If the irradiated area is the only site of disease, there must be evidence of progressive disease outside of the radiation field .
  • Uncontrolled adrenal insufficiency
  • Any active known or suspected autoimmune disease
  • Recent or active bleeding diathesis or arterial vascular event (including embolic arterial event such as cerebrovascular accident (or transient ischemic attacks) within 6 months of registration. NOTE: subjects with deep venous thrombosis or pulmonary embolism allowed even within 6 months if controlled on anticoagulation (such as warfarin or heparin provided that their medication dose and INR/PTT are stable)
  • Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter the study
  • Uncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management.
  • Active or clinically significant cardiac disease within 6 months including:

    • Symptomatic Congestive heart failure - New York Heart Association (NYHA)

      > Class II

    • Symptomatic Coronary artery disease (controlled clinically on medication allowed)
    • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin. Controlled atrial fibrillation is allowed.
    • Unstable angina or myocardial infarction.
  • Any hemorrhage or bleeding event ≥ NCI CTCAE v4 Grade 3 within 4 weeks prior to start of study medication.
  • Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from ccRCC except cervical cancer in-situ, treated localized basal cell carcinoma, Gleason score 6 prostate cancer or superficial bladder tumor.
  • Known current or chronic hepatitis B or C infection requiring treatment with antiviral therapy. (NOTE: testing not required)
  • Presence of non-healing wound, non-healing ulcer or bone fracture.
  • Renal failure requiring hemo- or peritoneal dialysis.
  • Persistent proteinuria ≥ Grade 3 NCI-CTCAE v4 (> 3.5 g/24hrs, measured by urine protein: creatinine ratio on a random urine sample)
  • Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)."
  • Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.
  • Pleural effusion or ascites that causes respiratory compromise (≥ Grade 2 dyspnea NCI-CTCAE v4)
  • History of organ allograft (including corneal transplant)
  • Known or suspected allergy or hypersensitivity to any drugs, study drug classes, or excipients of the formulations given during the course of this trial.
  • Any uncontrolled malabsorption condition
  • Any condition which in the site investigator's opinion, makes the subject unsuitable for trial participation.
  • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.

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): NCT03035630


Locations
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United States, Alabama
University of Alabama Hematology Oncology Clinic at Medical West
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
Guru Sonpavde
Hoosier Cancer Research Network
Pfizer
Investigators
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Study Chair: Guru Sonpavde, M.D. Hoosier Cancer Research Network

Additional Information:
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Responsible Party: Guru Sonpavde, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT03035630     History of Changes
Other Study ID Numbers: HCRN GU15-223
First Posted: January 30, 2017    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Guru Sonpavde, Hoosier Cancer Research Network:
Avelumab
Sunitinib
MSB0010718C
Sutent
IgG1 antibody
Anti-PD-L1
Tyrosine kinase inhibitor
Additional relevant MeSH terms:
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Protein Kinase Inhibitors
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Antibodies, Monoclonal
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors