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A Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Treatment

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01136733
First received: May 26, 2010
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

This is an open-label, multicenter, Phase 1b/2 study of E7080 alone and in combination with everolimus in subjects with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted treatment.


Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Drug: E7080
Drug: Everolimus
Drug: E7080 plus Everolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase 1b/2 Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Phase 1b=Dose-limiting toxicity (DLT) [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]
  • Phase 1b= Maximally tolerated dose (MTD [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]
  • Phase 1b= Recommended Phase 2 (RP2) dose [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]
  • Phase 2=Progression-free survival (PFS) [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Time is from Baseline to first evidence of disease progression.Assessments are performed every 2 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
  • Disease Control Rate (DCR) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
  • Durable Stable Disease (SD) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
    The portion of subjects whose best over all response is SD and the the duration of of SD > 23 weeks.

  • Clinical Benefit Rate (CBR) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic (PK) and pharmacodynamic (PD) profile. [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
    Plasma concentrations of E7080 and whole blood concentrations of everolimus at Cycle 1 days 1 and 15, Cycle 2 day 1 Cycle 3 Day 1


Estimated Enrollment: 180
Study Start Date: August 2010
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E7080 Drug: E7080
taken orally,once a day
Experimental: E7080 plus Everolimus Drug: E7080 plus Everolimus
orally once a day
Active Comparator: Everolimus Drug: Everolimus
orally once a day

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Select Inclusion Criteria:

  • Histologically confirmed diagnosis of renal cell carcinoma.
  • Phase 2: Histological or cytological confirmation of predominant clear cell RCC (original tissue diagnosis of RCC is acceptable).
  • Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic evidence of disease progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Phase 2: One prior vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) for unresectable advanced or metastatic RCC.
  • Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is serially measurable according to Modified RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.

Select Exclusion Criteria:

Phase 1b or Phase 2 specific per below:

  • Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous system (CNS) are excluded. Subjects who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are eligible for Phase 1b only. Phase 2 only: Subjects with CNS (e.g., brain or leptomeningeal) metastasis are excluded.
  • Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced or metastatic RCC.

Phase 1b or Phase 2 specific per below:

  • Phase 1b only: Prior exposure to E7080. Phase 2 only: Prior exposure to E7080 or mammalian target of rapamycin (mTOR) inhibitor.
  • Subjects should not have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. Major surgery within 3 weeks prior to the first dose of study drug.
  • Subjects having > 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
  • Subjects with urine protein greater than or equal to 1 g/24-hour will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose >1.5 X ULN.
  • Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
  • Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of the excipients.
  • Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136733

  Show 37 Study Locations
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Eisai Medical Services Eisai Limited
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01136733     History of Changes
Other Study ID Numbers: E7080-G000-205
Study First Received: May 26, 2010
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
Unresectable advanced or metastatic renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Endothelial Growth Factors
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014