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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Non Small Cell Lung Cancer

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Trial Information

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

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 ≥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.

Inclusion Criteria:

- Patients may be entered in the study only if they meet all of the following criteria:

1. Male or female patient greater than or equal to 18 years of age;

2. 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;

3. Have at least 1 site of measurable disease by the Response Evaluation Criteria
in Solid Tumors version 1.1 (RECIST) criteria;

4. 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

5. Life expectancy of greater than 3 months;

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) less than 1;

7. Patients must have adequate renal function as evidenced by calculated creatinine
clearance greater than 45 mL/min per the Cockcroft and Gault formula;

8. 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;

9. Patients must have adequate bone marrow function as evidenced by absolute
neutrophil count (ANC) greater than 1.5 X 109/L, hemoglobin greater than 9.0
g/dL (a hemoglobin <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 109/L;

10. 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;

11. 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;

12. Females of childbearing potential must have a negative serum pregnancy test;

13. Females may not be breastfeeding; and

14. Ability to understand and willingness to sign a written informed consent.

Exclusion Criteria:

- Patients may be entered in the study only if they meet all of the following criteria:

1. Prior treatment with pemetrexed, epothilone, ixabepilone, patupilone,
halichondrin B or halichondrin B-like compounds;

2. 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;

3. 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;

4. 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;

5. 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;

6. Are currently receiving any other treatment, including palliative radiotherapy
for the tumor aside from control of symptoms;

7. Common Toxicity Criteria (CTC) greater than Grade 3 peripheral neuropathy;

8. Require therapeutic doses of vitamin K antagonists;

9. Uncontrolled pleural effusions, ascites, or other third space fluid collections;

10. Uncontrolled diabetes mellitus Type 1 or 2; Significant cardiovascular
impairment (history of congestive heart failure > New York Heart Association
(NYHA) Grade II, unstable angina or myocardial infarction within the past 6
months, or serious cardiac arrhythmia);

11. Patients with organ allografts requiring immunosuppression;

12. Known positive human immunodeficiency virus (HIV), known hepatitis B surface
antigen, or hepatitis C positive;

13. Hypersensitivity to halichondrin B and/or halichondrin B chemical derivative; or
Have any medical condition that would interfere with the conduct of the study.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety parameters: adverse events (AEs); vital signs; EC0G PS; clinical laboratory evaluations; physical examinations; and 12 lead electrocardiograms (ECGs).

Outcome Time Frame:

Time Frame: AEs and conmeds - until study termination; lab tests Day 1 and every 21 days until study termination; ECGs - Day 1 and every 21 days while on therapy]

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

December 2014

Related Keywords:

  • Non Small Cell Lung Cancer
  • neoplams
  • lung neoplasms
  • Stage IIIB or IV Nonsquamous Non Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Rocky Mountain Cancer CenterDenver, Colorado  80218
Florida Cancer SpecialistsFort Myers, Florida  33901
Sarah Cannon Cancer CenterNashville, Tennessee  37203
Arizona Clinical Research Center, Inc.Tucson, Arizona  85712
Hematology Oncology Associates, SJ, P.A.Mount Holly, New Jersey  08060
Northwest Medical Specialities, PLLCTacoma, Washington  98405
Chattanooga Oncology and Hematology Associates PCChattanooga, Tennessee  37404