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Phase II Trial of Ixabepilone and Carboplatin With or Without Bevacizumab in Patients With Previously Untreated Advanced Non-Small-Cell Lung Cancer


Phase 2
18 Years
N/A
Not Enrolling
Both
Non-Small Cell Lung Cancer

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Trial Information

Phase II Trial of Ixabepilone and Carboplatin With or Without Bevacizumab in Patients With Previously Untreated Advanced Non-Small-Cell Lung Cancer


The trial will include a lead-in phase for each cohort to assess safety. In Cohort A, 10
patients will receive ixabepilone 30 mg/m2 and carboplatin AUC = 6 intravenously (IV) on Day
1 of one 21-day treatment cycle. If no unexpected toxicities occur, Cohort A will open to
enrollment. Enrollment for Cohort A will be done in two stages (after the lead-in portion
is completed). The first stage for Cohort A will enroll a total of 22 patients (this will
include the 10 patients from the lead-in phase). If there are at least 3 responses during
stage 1, enrollment for stage 2 will proceed. For stage 2 of the study, 17 additional
patients will be enrolled (for a total of 39 patients in Cohort A). During stage 1 and
stage 2, patients in Cohort A will receive treatment with ixabepilone 30 mg/m2 and
carboplatin AUC = 6 intravenously (IV) on Day 1 of each 21-day treatment cycle. Treatment
will continue until disease progression or unacceptable toxicity occurs.

After the lead-in phase for Cohort A is completed, a similar lead-in portion, also
consisting of 10 patients, will be done for Cohort B. Patients in Cohort B will receive
ixabepilone 30 mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on
Day 1 of one 21-day treatment cycle. If no unexpected toxicities occur in this group,
Cohort B will open to enrollment. Enrollment for Cohort B will also be done in two stages
(after the lead-in portion is completed). The first stage for Cohort B will enroll a total
of 22 patients (this will include the 10 patients from the lead-in phase). If there are at
least 3 responses during stage 1, enrollment for stage 2 will proceed. For stage 2 of the
study, 17 additional patients will be enrolled (for a total of 39 patients in Cohort B).
During stage 1 and stage 2, patients in Cohort B will receive treatment with ixabepilone 30
mg/m2, carboplatin AUC = 6 intravenously (IV), and bevacizumab 15 mg/kg on Day 1 of each
21-day treatment cycle. Treatment will continue until disease progression or unacceptable
toxicity occurs.

Unexpected toxicities include any grade 4 hematologic toxicity or grade 3/4 non hematologic
toxicity that does not reverse within 7 days in more than 2 patients.

Eligible patients will receive ixabepilone, carboplatin, and bevacizumab (bevacizumab will
be administered to patients in Cohort B only) at 21-day intervals. Patients will be re
evaluated every 6 weeks using computerized tomography (CT) scans. Response to therapy will
be assigned using Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse et al.
2000) (see Section 7). Patients who have objective response or stable disease will continue
treatment for 6 cycles, until the time of tumor progression or intolerable treatment-related
side effects. Patients in Cohort B without progressive disease will be eligible to receive
bevacizumab monotherapy for 6 additional cycles, or until undue toxicity or tumor
progression occurs.


Inclusion Criteria:



1. Histologically confirmed non-small-cell bronchogenic carcinoma (squamous carcinoma,
adenocarcinoma, or large cell carcinoma). Cytologic specimens obtained by brushings,
washings, or needle aspiration of the defined lesion are acceptable. Mixed tumors
with small-cell anaplastic elements are not eligible.

2. Patients who have newly diagnosed unresectable stage III or IV disease are eligible.
Patients with stage III disease should be ineligible for combined modality therapy

3. Patients must not have received any prior antineoplastic chemotherapy for metastatic
lung cancer prior to study entry.

4. Patients who have had previous radiotherapy as definitive therapy for locally
advanced non-small-cell are eligible as long as the recurrence is outside the
original radiation port. Radiation therapy must have been completed greater than 4
weeks prior to registration.

5. Male or female patients >=18 years of age.

6. Life expectancy of at least 3 months.

7. ECOG performance status of <=1.

8. Measurable disease by RECIST criteria (see Section 7).

9. Laboratory values as follows:

- ANC >=1500/mm3 (7 days prior to treatment);

- Hemoglobin >=8 g/dL;

- Platelets >=100,000 mm3 (7 days prior to treatment)

- Bilirubin <=1 x ULN for institution

- AST/SGOT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases and

- ALT/SGPT <=2.5 x ULN or <=5.0 x ULN in patients with liver metastases

- Creatinine <=2.0 mg/dL or

- Calculated (measured) GFR >=40 mL/min

- PT/INR and PTT <=1.5 x ULN

10. Peripheral neuropathy <= grade 1.

Exclusion Criteria:

1. A history of cardiac disease as defined by malignant hypertension, unstable angina,
congestive heart failure of > grade 2 per New York Heart Association (NYHA) criteria
(see Appendix B), myocardial infarction within the previous 6 months, or symptomatic
cardiac arrhythmias.

2. Metastatic brain or meningeal tumors.

3. Uncontrolled intercurrent illness.

4. Chemotherapy, investigational drug therapy, or major surgery ≤ 4 weeks prior to
starting study drug, or patients who have not recovered from side effects of previous
therapy.

5. Patient is <=5 years free of another primary malignancy, except if the other primary
malignancy is not currently clinically significant or requiring active intervention,
or if the other primary malignancy is a basal cell skin cancer or a cervical
carcinoma in situ.

Exclusion Criteria for Enrollment on Bevacizumab (Cohort B):

1. Patients with squamous cell histology NSCLC.

2. Patients who have had a major surgical procedure (not including mediastinoscopy),
open biopsy, or significant traumatic injury within 1 month of beginning bevacizumab.

3. Patients who have had primary thoracic radiation within 3 months of beginning
bevacizumab.

4. Fine needle aspiration, core biopsy, mediastinoscopy or other minor surgical
procedure within 7 days of beginning bevacizumab.

5. Patients receiving thrombolytic therapy within 10 days of starting bevacizumab.

6. Patients with serious non-healing wound, ulcer, or bone fracture.

7. Patients with evidence of bleeding diathesis or coagulopathy.

8. Patients with history of hemoptysis (defined as bright red blood of ½ teaspoon or
more per episode) within 3 months prior to study enrollment.

9. Patients with proteinuria at screening, as demonstrated by either:

- Urine protein : creatinine (UPC) ratio >=1.0 or

- Urine dipstick for protein >=2+ (patients discovered to have >=2+ proteinuria on
dipstick at baseline should undergo a 24-hour urine collection, and must
demonstrate <1 g of protein in 24 hours to be eligible).

10. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to beginning bevacizumab.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment

Outcome Description:

The Percentage of Patients Who Experience an Objective Benefit From Treatment

Outcome Time Frame:

18 months

Safety Issue:

No

Principal Investigator

David R Spigel, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sarah Cannon Research Insititute

Authority:

United States: Institutional Review Board

Study ID:

SCRI LUN 179

NCT ID:

NCT00741988

Start Date:

September 2008

Completion Date:

September 2012

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Non-Small Cell Lung Cancer
  • Advanced Disease
  • Untreated
  • Ixabepilone
  • Carboplatin
  • Bevacizumab
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms

Name

Location

Florida Cancer SpecialistsFort Myers, Florida  33901
Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Research Medical CenterKansas City, Missouri  64132
Consultants in Blood Disorders and CancerLouisville, Kentucky  40207
South Carolina Oncology AssociatesColumbia, South Carolina  29201
Peninsula Cancer InstituteNewport News, Virginia  23601
Center for Cancer and Blood DisordersBethesda, Maryland  20817
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Tennessee Oncology, PLLCClarksville, Tennessee  37043
Oncology Hematology CareCincinnati, Ohio  45242
Gainsville Hematology Oncology AssociatesGainesville, Florida  32605
Providence Medical GroupTerre Haute, Indiana  47802
Dr. Donald BerdeauxGreat Falls, Montana  59405