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

NCT03035630 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU15-223
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Clear-cell Renal Cell Carcinoma; RCC; Kidney Cancer; Clear-cell Kidney Carcinoma

Keywords

Avelumab; Sunitinib; MSB0010718C; Sutent; IgG1 antibody; Anti-PD-L1; Tyrosine kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• Overall Progression-Free Survival (PFS)

  Compare PFS1 + PFS2 rates for overall PFS

  up to 24 months

Secondary Outcomes (4)

• Overall Failure-Free Survival (FFS)

  up to 24 months

• Overall Survival (OS)

  up to 36 months

• Overall Response Rate (RR)

  2 years

• Overall Toxicities

  up to 36 months

Study Arms (2)

Avelumab then Sunitinib for Investigational Arm A

EXPERIMENTAL

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; Drug: Sunitinib

Sunitinib then Avelumab for Investigational Arm B

EXPERIMENTAL

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; Drug: Sunitinib

Interventions

Avelumab DRUG

Avelumab 10mg/kg IV over 60 minutes on D1 and D15 of every 28 day cycle

Also known as: MSB0010718C

Avelumab then Sunitinib for Investigational Arm A; Sunitinib then Avelumab for Investigational Arm B

Sunitinib DRUG

Sunitinib 50 mg once daily from D1 to D14 of every 21 day cycle

Also known as: Sutent

Avelumab then Sunitinib for Investigational Arm A; Sunitinib then Avelumab for Investigational Arm 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 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guru Sonpavde: lead
• Hoosier Cancer Research Network: collaborator
• Pfizer: collaborator

Study Sites (1)

University of Alabama Hematology Oncology Clinic at Medical West

Birmingham, Alabama, 35294, United States

Location

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

avelumab; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Guru Sonpavde, M.D.

  Hoosier Cancer Research Network

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: January 24, 2017
• First Posted: January 30, 2017
• Study Start: May 23, 2017
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2020
• Last Updated: February 15, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)