Trial of Poor Performance Status Patients (ToPPS)

Non Small Cell Lung Cancer Clinical Trial

— ToPPS  

Official title:

Randomized Phase II Trial of Pemetrexed vs. Pemetrexed/Bevacizumab vs. Pemetrexed/Carboplatin/Bevacizumab in Patients With Stage IIIB/IV Non-Small-Cell Lung Cancer and ECOG Performance Status 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00892710
• Other study ID #: SCRI LUN 196
• Status: Completed
• Phase: Phase 2
• First received: April 30, 2009
• Last updated: May 12, 2015
• Start date: June 2009
• Est. completion date: May 2015

Study information

• Verified date: May 2015
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to evaluate three treatment regimens in patients with stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) with a performance status of 2 and who were not previously treated.

Description:

This randomized, Phase II trial will evaluate three treatment regimens in patients with previously untreated stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) and a performance status (PS) of 2. Patients will be randomized to either pemetrexed alone, pemetrexed and bevacizumab, or pemetrexed, carboplatin, and bevacizumab in a 1:1:1 fashion. All 3 regimens should be tolerable in poor performance status patients with advanced NSCLC. The 3-drug regimen (pemetrexed/carboplatin/bevacizumab) has been modified by lowering the dose of carboplatin, in order to minimize myelosuppression. This trial will be conducted at multiple study sites.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 172
• Est. completion date: May 2015
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must be >=18 years of age.

2. Non-squamous NSCLC (adenocarcinoma or large cell carcinoma). Mixed tumors with small cell anaplastic elements are not eligible. Mixed tumors with squamous histology are acceptable as long as the squamous element is not the dominant histology.

3. Unresectable stage IIIB or stage IV disease. Stage IIIB disease should be ineligible for combined modality therapy (i.e., pleural effusions, pericardial effusions).

4. ECOG performance status of 2.

5. No prior systemic therapy for stage IIIB or stage IV lung cancer.

6. Life expectancy of at least 12 weeks.

7. Patients must have measurable disease per RECIST version 1.1 (see Section 8).

8. Laboratory values as follows:

• Absolute neutrophil count (ANC) =1500/µL

• Hemoglobin (Hgb) =10 g/dL

• Platelets =100,000/µL (=7 days prior to treatment)

• AST or ALT and alkaline phosphatase (ALP) must be <2.5 x ULN, or <5 x ULN in patients with liver metastases.

• Total bilirubin <1.5 x the institutional ULN

• Calculated creatinine clearance =45 mL/min

9. The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.

10. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.

11. Patient must be accessible for treatment and follow-up.

12. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Exclusion Criteria:

1. Squamous cell histology. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient will be ineligible; sputum cytology alone is unacceptable.

2. Patients with active brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 2 weeks have elapsed since treatment. Ideally, patients should not still require use of seizure medication or steroids.

3. Patients who have had major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury within 4 weeks of beginning treatment; or, the anticipation of the need for major surgical procedure during the course of the study.

4. Women who are pregnant or lactating.

5. Minor surgical procedures (with the exception of the placement of portacath or other central venous access) must be completed at least 7 days prior to beginning protocol treatment.

6. History of hypersensitivity to active or inactive excipients of any component of treatment (pemetrexed, bevacizumab, and/or carboplatin).

7. Pulmonary carcinoid tumors.

8. Patients with proteinuria at screening as demonstrated by either:

• urine protein creatinine (UPC) ratio =1.0 at screening OR

• urine dipstick for proteinuria =2+ (patients discovered to have =2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection, and must demonstrate =1 g of protein/24 hours to be eligible) (see Appendix B)

9. Patients with a serious non healing wound, active ulcer, or untreated bone fracture.

10. Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).

11. Patients with history of hematemesis or hemoptysis (defined as having bright red blood of ½ teaspoon or more per episode) within 1 month prior to study enrollment.

12. History of myocardial infarction or unstable angina within 6 months of beginning treatment.

13. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and /or diastolic blood pressure >100 mmHg while on antihypertensive medications).

14. New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF) (see Appendix C).

15. Serious cardiac arrhythmia requiring medication.

16. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of treatment.

17. History of stroke or transient ischemic attack = 6 months prior to beginning treatment.

18. Any prior history of hypertensive crisis or hypertensive encephalopathy.

19. History of abdominal fistula or gastrointestinal perforation = 6 months prior to Day 1 of beginning treatment.

20. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.

21. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.

22. Use of any non-approved or investigational agent = 30 days of administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.

23. Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a DFS =5 years.

Study Design

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Pemetrexed
500 mg/m2 IV given over 10 minutes every 21 days
• Bevacizumab
15 mg/kg IV every 21 days
• Carboplatin
AUC=5 IV every 21 days

Locations

Country	Name	City	State
United States	Aventura Medical Center	Aventura	Florida
United States	Collaborative Research Group/ Palm Beach Ins of Hem Onc	Boynton Beach	Florida
United States	Medical University of South Carolina	Charlston	South Carolina
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	University of Chicago	Chicago	Illinois
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	South Carolina Oncology Associates, PA	Columbia	South Carolina
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Holy Cross Hospital	Ft. Lauderdale	Florida
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Memorial Regional Cancer Center	Hollywood	Florida
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	Northeast Arkansas Clinic	Jonesboro	Arkansas
United States	Watson Clinic Center for Cancer Care and Research	Lakeland	Florida
United States	Wilshire Oncology Medical Group	LaVerne	California
United States	Family Cancer Center	Memphis	Tennessee
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Hematology Oncology Associates of Northern NJ	Morristown	New Jersey
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Mayo Clinic - AZ	Scottsdale	Arizona
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	RHHP/ Hope Cancer Center	Terra Haute	Indiana
United States	Toledo Community Oncology Program	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	18 months	No
Secondary	Overall Response Rate (ORR), the Number of Patients Who Experience an Objective Benefit From Treatment	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	18 months	No
Secondary	Time to Progression (TTP)	The Length of Time, in Months, That Patients Remain Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	18 months	No
Secondary	Time to Treatment Failure (TTTF)	Defined as the Length of Time, in Months, that Patients were Alive from the Date of First Treatment Until Treatment Discontinuation for Any Reason.	18 months	No
Secondary	Overall Survival (OS)	The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death	18 months	No
Secondary	6-month and 12-month Overall Survival Probability	Overall Survival = The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death	12 months	No