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Trial record 1 of 1 for:    NCT03472560
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A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03472560
Recruitment Status : Active, not recruiting
First Posted : March 21, 2018
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE February 28, 2018
First Posted Date  ICMJE March 21, 2018
Last Update Posted Date July 31, 2020
Actual Study Start Date  ICMJE May 2, 2018
Estimated Primary Completion Date June 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2018)
Confirmed objective response [ Time Frame: Baseline up to approximately 18 months ]
Objective response (OR) is defined as a confirmed complete response (CR) or partial (PR) per RECIST v 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2018)
  • Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 18 months ]
    Time to Tumor Response (TTR) is defined as the time from the date of first dose of study treatment to the first documentation of objective response [complete response (CR) or partial response (PR)].
  • Tumor tissue biomarker status (ie, positive or negative based on, for example, PD L1 expression and/or quantitation of tumor mutational burden as well as characterization of the immune repertoire in peripheral blood and/or tumor) [ Time Frame: Screening and optional tumor biopsies obtained upon disease progression. Baseline up to approximately 18 months. ]
    Archived tumor tissue samples and de novo biopsies of primary and/or metastatic lesions. Tumor tissue biomarker status (ie, positive or negative based on, for example, PD L1 expression and/or quantitation of tumor mutational burden as well as characterization of the immune repertoire in peripheral blood and/or tumor).
  • Anti-drug antibody (ADA) titers against avelumab [ Time Frame: Pre dose on Cycle 1 Day 1 and Day 15, Cycle 2 Day 1, and Day 15 of Cycles 3, 6, 9 and 12 (each cycle is 28 days) ]
    Immunogenicity assessment of avelumab.
  • Duration of Response (DR) [ Time Frame: Baseline up to approximately 18 months ]
    Duration of Response (DR), is defined as the time from the first documentation of objective response [complete response (CR) or partial response (PR)] to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.
  • Progression Free Survival (PFS) [ Time Frame: Baseline up to approximately 18 months ]
    Progression Free Survival (PFS) is defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.
  • Maximum Observed Plasma Concentration (Cmax) of axitinib [ Time Frame: 2-4 hours post dose Cycle 1 Day 15 and Cycle 2 Day 1 and Day 15 (each cycle is 28 days) ]
    Cmax defined as the maximum plasma concentration of axitinib
  • Predose Concentration (Ctrough) of avelumab [ Time Frame: Pre dose Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 and Day 15 of Cycles 3, 6, 9, and 12 (each cycle is 28 days) ]
    Ctrough is defined as the concentration at the end of avelumab dosage interval
  • Predose concentration (Ctrough) of axitinib [ Time Frame: Pre dose Cycle 1 Day 15 and Cycle 2 Day 1 and Day 15 (each cycle is 28 days) take up to 2 hr prior to the start of infusion. ]
    Ctrough is defined as the concentration at the end of axitinib dosage interval
  • Neutralizing antibodies (nAb) against avelumab [ Time Frame: Pre dose on Cycle 1 Day 1 and Day 15, Cycle 2 Day 1, and Day 15 of Cycles 3, 6, 9 and 12 (each cycle is 28 days) ]
    Immunogenicity assessment of avelumab.
  • Maximum Observed Plasma Concentration (Cmax) of avelumab [ Time Frame: Post dose Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 (each cycle is 28 days) ]
    Cmax defined as the maximum plasma concentration of avelumab
  • Overall Survival (OS) [ Time Frame: Baseline up to approximately 18 months ]
    Overall Survival (OS) is defined as the time from the date of first dose of study treatment to the date of death due to any cause.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF)
Official Title  ICMJE A PHASE 2, OPEN LABEL STUDY TO EVALUATE SAFETY AND CLINICAL ACTIVITY OF AVELUMAB (BAVENCIO (REGISTERED)) IN COMBINATION WITH AXITINIB (INLYTA (REGISTERED)) IN PATIENTS WITH ADVANCED OR METASTATIC PREVIOUSLY TREATED NON-SMALL CELL LUNG CANCER OR TREATMENT NAÏVE CISPLATIN-INELIGIBLE UROTHELIAL CANCER JAVELIN MEDLEY VEGF
Brief Summary This is a Phase 2 study to evaluate the safety and efficacy of avelumab in combination with axitinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior platinum containing therapy, and in treatment naïve patients with advanced or metastatic urothelial cancer, who are ineligible for cisplatin containing chemotherapy for their advanced disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Small Cell Lung Cancer
  • Urothelial Cancer
Intervention  ICMJE
  • Drug: Avelumab (MSB0010718C)
    IV treatment: Avelumab administered at 800 mg IV every two weeks
    Other Name: Bavencio
  • Drug: Axitinib (AG-013736)
    Oral treatment: Axitinib given 5 mg PO BID
    Other Name: Inlyta
Study Arms  ICMJE Experimental: Avelumab in combination with axitinib
Avelumab administered at 800 mg IV every two weeks in combination with axitinib, 5 mg PO BID.
Interventions:
  • Drug: Avelumab (MSB0010718C)
  • Drug: Axitinib (AG-013736)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 16, 2020)
61
Original Estimated Enrollment  ICMJE
 (submitted: March 20, 2018)
80
Estimated Study Completion Date  ICMJE June 28, 2022
Estimated Primary Completion Date June 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Non-small cell lung cancer (NSCLC) Cohort: Histologically or cytologically confirmed diagnosis of NSCLC that is locally advanced or metastatic; No activating EGFR mutations, ALK or ROS1 translocations/rearrangements where testing is standard of care; received at least 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic NSCLC; No more than 2 prior lines of systemic therapy for locally advanced or metastatic disease (If disease progression occurred during or within 6 months after neoadjuvant/adjuvant chemotherapy or radiotherapy-chemotherapy, the regimen is counted as 1 prior treatment regimen towards the allowed limit of prior treatment regimens); Checkpoint inhibitor naïve.
  • Urothelial Cancer (UC) Cohort: Histologically or cytologically confirmed diagnosis of transitional cell carcinoma (TCC) of the urothelium (if mixed, more than 50% TCC component) including bladder, urethra, ureters, or renal pelvis that is locally advanced or metastatic; No prior systemic treatment for locally advanced or metastatic disease; Prior neoadjuvant or adjuvant therapy is permitted if disease progression occurred >12 months after the completion of therapy; Checkpoint inhibitor naïve; Ineligible for receiving cisplatin-containing front-line chemotherapy based at least one of the following criteria: ECOG performance status (PS) 2; Renal dysfunction (defined as creatinine-clearance <60 ml/min); Grade 2 peripheral neuropathy; Grade 2 hearing loss (hearing loss measured by audiometry of 25 decibels at two contiguous frequencies).
  • At least 1 measurable lesion by RECIST v1.1 not previously irradiated.
  • Availability of an archival FFPE tumor tissue block from primary diagnosis specimen or metastatic specimen or 15 unstained slides (10 minimum). If an archived sample is not available, a fresh tumor biopsy must be performed.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. For UC patients, ECOG performance 2 is permitted (cisplatin ineligibility criterion)

Exclusion Criteria:

  • Prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-GITR, anti-LAG-3, anti-TIM-3 or anti-CTLA-4 antibody (including ipilimumab).
  • Newly diagnosed brain metastases or known symptomatic brain metastases requiring steroids.
  • Radiologically documented evidence of major blood vessel invasion or encasement by cancer or intratumor cavitation, regardless of tumor histology.
  • Active autoimmune disease (that might deteriorate when receiving an immunostimulatory agent).
  • Current use of immunosuppressive medication (except for those listed in protocol).
  • Known prior severe hypersensitivity to the investigational products /monoclonal antibodies.
  • Known history of immune-mediated colitis, inflammatory bowel disease, immune-mediated pneumonitis, pulmonary fibrosis.
  • NCI CTCAE Grade 3 hemorrhage within 28 days prior to study enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hungary,   Italy,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03472560
Other Study ID Numbers  ICMJE B9991027
2017-004345-24 ( EudraCT Number )
AVE/ AXI COMBO UC ( Other Identifier: Alias Study Number )
AVE/AXI COMBO UC/NSCLC ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP