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NCT01136733 · OUTCOME

Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT)

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 · Source last updated 2019-02-27

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
NUMBER
Unit
Participants
Interval / dispersion
Not reported
Time frame
First dose of study drug (Cycle 1 Day 1) to end of first 4 weeks of therapy (Cycle 1)

What was measured

A DLT was defined as either a treatment-related failure to administer greater than or equal to (\>=) 75% of the planned dosage of lenvatinib/everolimus or a specific National Cancer Institute Common Toxicity Criteria (NCI CTC) \>= Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care daily living activities) hematologic or nonhematologic toxicities considered to be possibly related to lenvatinib and/or everolimus therapy assessed during the first treatment cycle of each dose level. Higher grade indicates more severe toxicity.

Analysis population: Safety analysis set included all participants who received at least one dose of study treatment.

Groups in this outcome

Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus

Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2. If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.

Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus

Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.

Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus

Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.

Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus

The DLT was achieved and no participants were enrolled into this cohort.

Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus

Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.

Phase 2 (Arm B): 24 mg Lenvatinib

Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.

Phase 2 (Arm C): 10 mg Everolimus

Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus7
Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus11
Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus2
Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus0
Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus0
Phase 2 (Arm B): 24 mg Lenvatinib0
Phase 2 (Arm C): 10 mg Everolimus0

Reported measurements

Grade 3 abdominal pain
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus1Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Grade 2 fatigue with Grade 1 GI reflux & anorexia
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus1Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Grade 3 nausea
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus1Not reportedNot reportedNot reportedNot reported
Grade 2 stomatitis
Values in Participants · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus0Not reportedNot reportedNot reportedNot reported
Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus1Not reportedNot reportedNot reportedNot reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        value
        1
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        0
    title
    Grade 3 abdominal pain
  2. categories
    1. measurements
      1. group Id
        OG000
        value
        0
      2. group Id
        OG001
        value
        1
      3. group Id
        OG002
        value
        0
    title
    Grade 2 fatigue with Grade 1 GI reflux & anorexia
  3. categories
    1. measurements
      1. group Id
        OG000
        value
        0
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        1
    title
    Grade 3 nausea
  4. categories
    1. measurements
      1. group Id
        OG000
        value
        0
      2. group Id
        OG001
        value
        0
      3. group Id
        OG002
        value
        1
    title
    Grade 2 stomatitis
denoms
  1. counts
    1. group Id
      OG000
      value
      7
    2. group Id
      OG001
      value
      11
    3. group Id
      OG002
      value
      2
    4. group Id
      OG003
      value
      0
    5. group Id
      OG004
      value
      0
    6. group Id
      OG005
      value
      0
    7. group Id
      OG006
      value
      0
    units
    Participants
description
A DLT was defined as either a treatment-related failure to administer greater than or equal to (\>=) 75% of the planned dosage of lenvatinib/everolimus or a specific National Cancer Institute Common Toxicity Criteria (NCI CTC) \>= Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care daily living activities) hematologic or nonhematologic toxicities considered to be possibly related to lenvatinib and/or everolimus therapy assessed during the first treatment cycle of each dose level. Higher grade indicates more severe toxicity.
groups
  1. description
    Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2. If 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.
    id
    OG000
    title
    Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus
  2. description
    Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
    id
    OG001
    title
    Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus
  3. description
    Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3. If 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.
    id
    OG002
    title
    Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus
  4. description
    The DLT was achieved and no participants were enrolled into this cohort.
    id
    OG003
    title
    Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus
  5. description
    Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.
    id
    OG004
    title
    Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus
  6. description
    Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.
    id
    OG005
    title
    Phase 2 (Arm B): 24 mg Lenvatinib
  7. description
    Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.
    id
    OG006
    title
    Phase 2 (Arm C): 10 mg Everolimus
param Type
NUMBER
population Description
Safety analysis set included all participants who received at least one dose of study treatment.
reporting Status
POSTED
time Frame
First dose of study drug (Cycle 1 Day 1) to end of first 4 weeks of therapy (Cycle 1)
title
Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT)
type
PRIMARY
unit Of Measure
Participants

Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0

Preserved source evidence · Not medical advice