AzTrials
AzTrials

Non Small Cell Lung CancerPhase 1/2NCT01126736

Eribulin Mesylate Administered in Combination With Pemetrexed Versus Pemetrexed Alone as Second Line Therapy in Patients With Stage IIIB or IV Nonsquamous Non Small Cell Lung Cancer

A Phase 1/2 study testing eribulin mesylate, pemetrexed and Eribulin mesylate (eribulin; E7389) in people with Non Small Cell Lung Cancer, run by Eisai Inc. at 18 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine whether Eribulin Mesylate Administered in Combination with Pemetrexed is safe and tolerable and to gain a preliminary indication of clinical benefit when administered to Patients with Stage IIIB or IV Nonsquamous Non Small Cell Lung Cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
eribulin mesylate, pemetrexed and Eribulin mesylate (eribulin; E7389)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
18 sitesin 5 countries
Study dates
10 Jun 2010to 18 Mar 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients may be entered in the study only if they meet all of the following criteria:
  • Male or female patient greater than or equal to 18 years of age;
  • Histologically or cytologically confirmed nonsquamous NSCLC stage IIIB with malignant pleural effusion or stage IV disease not amenable to curative therapy. Patients with history of stage III disease that have relapsed after chemo- and radiotherapy are also eligible;
  • Have at least 1 site of measurable disease by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) criteria;
  • Have failed 1 prior platinum-doublet containing chemotherapy regimen for stage IIIB with malignant pleural effusion or stage IV nonsquamous NSCLC. One additional cytotoxic regimen is allowed for neoadjuvant, adjuvant, or neoadjuvant plus adjuvant therapy for Phase II patients. For patients enrolled in the Phase Ib portion, a maximum of three total prior regimens is allowed.
  • Definition of a Chemotherapy Regimen: Any platinum-doublet containing chemotherapy, that may also include biological or targeted agents, and/or humanized antibodies, given concomitantly, sequentially, or both, is considered 1 regimen. If, due to toxicity, the dosing of 1 or more of the components must be reduced, or 1 or more of the components of the regimen must be omitted, or 1 of the components must be replaced with another similar drug, the changed version of the original regimen is not considered a new regimen. However, if a new component, dissimilar to any of the original components, is added to the regimen, the new combination is considered a new regimen. If the treatment is interrupted for surgery or radiotherapy, and then continues with an unchanged schedule and components, that treatment is considered as one regimen despite the interruption.
Show all 16Show fewer
  • Life expectancy of greater than 3 months;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) less than 1;
  • Patients must have adequate renal function as evidenced by calculated creatinine clearance greater than 45 mL/min per the Cockcroft and Gault formula;
  • Patients receiving daily treatment with non-steroidal anti-inflammatory agents (NSAIDS) are eligible. Patients with creatinine clearance 45-79 ml/min must be able to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed;
  • Patients must have adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than 1.5 x 10^9/L, hemoglobin greater than 9.0 g/dL (a hemoglobin less than 9.0 g/dL at Screening is acceptable if it is corrected to greater than 9 g/dL by growth factor or transfusion prior to first dose), and platelet count greater than 100 x 10^9/L;
  • Patients must have adequate liver function as evidenced by bilirubin less than 1.5 times the upper limit of the normal range (ULN), and alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 x ULN (in the case of liver metastases, less than 5 x ULN). If there are bone metastases, liver-specific alkaline phosphatase may be separated from the total and used to assess liver function instead of total alkaline phosphatase;
  • Male or female patients of child-producing potential must agree to use double barrier contraception, oral contraceptives, or avoidance of pregnancy measures during the study and for 90 days after the last day of treatment;
  • Females of childbearing potential must have a negative serum pregnancy test;
  • Females may not be breastfeeding; and
  • Ability to understand and willingness to sign a written informed consent.

Who cannot join

  • Patients may be entered in the study only if they meet all of the following criteria:
  • Prior treatment with pemetrexed, epothilone, ixabepilone, patupilone, halichondrin B or halichondrin B-like compounds;
  • Received chemotherapy, targeted therapy, radiotherapy, surgery, or immunotherapy within the 30 days prior to commencing study treatment or have not recovered from all treatment-related toxicities to Grade less than 1, except for alopecia;
  • History of other malignancies except: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated, a) in situ carcinoma of the uterine cervix, b) prostate cancer, or c) superficial bladder cancer; or (3) other curatively treated solid tumor with no evidence of disease for greater than 5 years;
  • Presence of brain metastases, unless the patient has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization;
  • Received treatment in another clinical study within the 30 days prior to commencing study treatment or patients who have not recovered from side effects of an investigational drug to Grade less than 1, except for alopecia;
Show all 14Show fewer
  • Are currently receiving any other treatment, including palliative radiotherapy for the tumor aside from control of symptoms;
  • Common Toxicity Criteria (CTC) greater than Grade 3 peripheral neuropathy;
  • Require therapeutic doses of vitamin K antagonists;
  • Uncontrolled pleural effusions, ascites, or other third space fluid collections;
  • Uncontrolled diabetes mellitus Type 1 or 2; Significant cardiovascular impairment (history of congestive heart failure greater than New York Heart Association (NYHA) Grade II, unstable angina or myocardial infarction within the past 6 months, or serious cardiac arrhythmia);
  • Patients with organ allografts requiring immunosuppression;
  • Known positive human immunodeficiency virus (HIV), known hepatitis B surface antigen, or hepatitis C positive;
  • Hypersensitivity to halichondrin B and/or halichondrin B chemical derivative; or Have any medical condition that would interfere with the conduct of the study.

Trial locations and contacts

18 sites in 5 countries.

18 sites in 5 countries

United States6 sites

  • Study site

    Denver, Colorado, 80218

  • Study site

    Fort Myers, Florida, 33916

  • Study site

    Mount Holly, New Jersey

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    Tacoma, Washington, 98405

  • Study site

    Tucson, Arizona, 85715

Other trials in United States

Ukraine6 sites

  • Study site

    Dnipropetrovsk, 49102

  • Study site

    Donetsk, 83092

  • Study site

    Kharkiv, 61024

  • Study site

    Kyiv

  • Study site

    Lviv, 79031

  • Study site

    Sumy, 40005

Other trials in Ukraine

Czechia2 sites

  • Study site

    Prague, 15006

  • Study site

    Prague, 18100

Other trials in Czechia

Germany2 sites

  • Study site

    Freiburg im Breisgau, 79106

  • Study site

    Heidelberg, 69126

Other trials in Germany

Italy2 sites

  • Study site

    Milan, 20132

  • Study site

    Rome

Other trials in Italy

About this study

Official title: An Open-Label, Multicenter, Randomized Phase Ib/II Study of Eribulin Mesylate Administered in Combination With Pemetrexed Versus Pemetrexed Alone as Second Line Therapy in Patients With Stage IIIB or IV Nonsquamous Non Small Cell Lung Cancer

The purpose of this study is to determine whether Eribulin Mesylate Administered in Combination with Pemetrexed is safe and tolerable and to gain a preliminary indication of clinical benefit when administered to Patients with Stage IIIB or IV Nonsquamous Non Small Cell Lung Cancer.

Read the detailed description

This open-label, multicenter, randomized study will consist of a Phase Ib portion: a safety run-in period with 3 ascending doses of eribulin; and a Phase II portion: a randomized 3-arm design. .

Phase Ib-Patients will be recruited into cohorts, into one of two parallel arms evaluating different eribulin dosing schedules (Arm 1: eribulin on Day 1; Arm 2: eribulin on Days 1 and 8), with a minimum of 3 and a maximum of 6 patients per cohort. All patients will receive pemetrexed (500 mg/m2) in combination with eribulin. All patients in a cohort will receive the same dose level of eribulin and there will not be any intra-patient dose escalation.

The dose level of eribulin will be escalated for additional cohorts in each of the two arms unless greater than or equal to 2 dose limiting toxicities (DLTs) are reported at the lower dose level(s) prior to enrollment of the next dose level.

Phase II- Patients will be randomized in a 1:1:1 ratio to receive either eribulin in combination with pemetrexed, in each of two dosing schedules (Arms 1 and 2), or pemetrexed alone (Arm 3). For both the Phase Ib and II portions, 1 cycle of therapy will last 21 days, with an estimated number of 6 cycles. Radiologic examinations including a computed tomography (CT) scan of the chest, abdomen, and pelvis as appropriate (and CT or magnetic resonance imaging [MRI] as appropriate), will be performed during Screening and thereafter every 2 cycles until disease progression.

Being tested
eribulin mesylate, pemetrexed, Eribulin mesylate (eribulin; E7389)
Keywords
neoplams, lung neoplasms, Stage IIIB, IV Nonsquamous Non Small Cell Lung Cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • eribulin mesylateDrug

    Also called halichrondrin B analog; Alimta

    Eribulin mesylate (eribulin; E7389) administered as a 2-5 minute intravenous (IV) bolus in one of two dosing schedules for both the Phase Ib and Phase 2 portions: either Days 1 and 8 of a 21 day cycle in ascending doses of 0.7, 1.1, or 1.4 mg/m2 or on Day 1 of the 21-day cycle at doses at ascending doses of 0.9, 1.4, or 2.0 mg/m2.

  • pemetrexedDrug

    Also called halichrondrin B analog; Alimta

    Pemetrexed given at a dose of 500 mg/m2 as an IV infusion on Day 1 of a 21-day cycle. Patients will also receive dexamethasone and vitamin supplements as recommended in the prescribing information for pemetrexed.

  • Eribulin mesylate (eribulin; E7389)Drug

    Eribulin mesylate (eribulin; E7389) administered as a 2-5 minute intravenous (IV) bolus in one of two dosing schedules for both the Phase Ib and Phase 2 portions: either Days 1 and 8 of a 21 day cycle in ascending doses of 0.7, 1.1, or 1.4 mg/m2 or on Day 1 of the 21-day cycle at doses at ascending doses of 0.9, 1.4, or 2.0 mg/m2.

Study groups in NCT01126736
Study groupRoleWhat they receive
Low Dose E7389 in Combination with PemetrexedExperimentalNot described
Receives: Drug: eribulin mesylate
PemetrexedActive comparatorNot described
Receives: Drug: pemetrexed
High Dose E7389 in Cominbation with PemetrexedExperimentalEribulin mesylate (eribulin; E7389) administered as a 2-5 minute intravenous (IV) bolus in one of two dosing schedules for both the Phase Ib and Phase 2 portions: either Days 1 and 8 of a 21 day cycle in ascending doses of 0.7, 1.1, or 1.4 mg/m2 or on Day 1 of the 21-day cycle at doses at ascending doses of 0.9, 1.4, or 2.0 mg/m2.
Receives: Drug: Eribulin mesylate (eribulin; E7389)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs)

    DLT were defined as clinically significant adverse events (AE) occurring less than or equal to (<=) 21 days after treatment. Events as: Non-hematological: 1) Grade greater than or equal to (>=) 3 peripheral neuropathy; 2) Grade >=3 nausea, vomiting despite optimal antiemetic treatment; 3) Any nonhematologic toxicity of Grade >=3, with exceptions as alopecia, single laboratory values out of normal range, hypersensitivity reaction. Hematological:1) Grade 4 neutropenia lasting >7 days; 2) Febrile neutropenia as fever >=38.5 degree Celsius with absolute neutrophil count less than (<)1.0*10^9 per liter(/L); 3) Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4) Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1) Study drug related death; 2) Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria.

    Measured: Cycle 1 (cycle length=21 days)

  2. Phase 1b: Percentage of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs)

    Safety assessment included monitoring and recording all AE including all Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grades (for both increasing and decreasing severity), and serious adverse events (SAE); regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and performance of physical examinations. A TEAE was defined as an AE that had on onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to the end of the study. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.

    Measured: From date of first dose up to 30 days after the last dose of study drug in Phase 1b, up to approximately 1 year 2 months

  3. Phase 2: Percentage of Participants Who Experienced TEAEs

    Safety assessment included monitoring and recording all AE including all CTCAE version 4.0 grades (for both increasing and decreasing severity), and SAE; regular monitoring of hematology, blood chemistry, and urine values; periodic measurement of vital signs and ECGs; and performance of physical examinations. A TEAE was defined as an AE that had on onset date, or a worsening in severity from Baseline (pretreatment), on or after the first dose of study drug up to the end of the study.

    Measured: From date of first dose up to 30 days after the last dose of study drug in Phase 2, up to approximately 3 years 6 months

Secondary outcomes (1)

  1. Phase 2: Progression-free Survival (PFS)

    PFS was defined as the time from the date of randomization until the earlier of the following two events: the date of progressive disease (PD) or the date of death. Progressive disease was defined as at least a 20 percent (%) increase in the sum of the longest diameter of target lesions (taking as reference the smallest sum on study), recorded since the treatment started or the appearance of 1 or more new lesions based on investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). If a participant did not progress, they were censored at the date of last tumor assessment, last known alive date, or until the start of a next line of therapy, whichever occurred first. PFS was estimated using Kaplan-Meier method and presented with 2-sided 95% confidence interval.

    Measured: From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 3 years 5 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2010 (estimated)
  2. Study start10 Jun 2010
  3. Primary completion31 Dec 2012
  4. Study completion18 Mar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01126736
Sponsor's protocol ID
E7389-701
Other IDs
2009-016047-19, 2009
Status last verified
Jul 2022
First submitted
17 May 2010
Last updated
22 Jun 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing eribulin mesylate, pemetrexed and Eribulin mesylate (eribulin; E7389) in people with Non Small Cell Lung Cancer, run by Eisai Inc. at 18 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Ukraine, Czechia, Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) (time frame: Cycle 1 (cycle length=21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01126736.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in