Trial of Poor Performance Status Patients (ToPPS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT00892710
First received: April 30, 2009
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

This randomized, Phase II trial will serve to evaluate three treatment regimens in patients with previously untreated stage IIIB/IV NSCLC and a 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 (AUC 6.0 to 5.0), in order to minimize myelosuppression. This trial will be conducted at multiple study sites. [NOTE: Effective January 2013 Arm-1 will stop enrolling patients.]


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: Pemetrexed
Drug: Bevacizumab
Drug: Carboplatin
Phase 2

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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Progression Free Survival (PFS), the Length of Time, in Months, That Patients Remain Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease or Death [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Time to Treatment Failure (TTTF), the Length of Time, in Months, that Patients were Alive from the Date of First Treatment Until Treatment Discontinuation for Any Reason. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Assess overall survival, 6-month survival, and 1-year survival. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 183
Study Start Date: June 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pemetrexed/Bevacizumab
  • Pemetrexed 500 mg/m2 IV given over 10 minutes every 21 days
  • Bevacizumab 15 mg/kg IV every 21 days
Drug: Pemetrexed
500 mg/m2 IV given over 10 minutes every 21 days
Other Name: Alimta
Drug: Bevacizumab
15 mg/kg IV every 21 days
Other Name: Avastin
Experimental: Pemetrexed/Bevacizumab/Carboplatin
  • 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
Drug: Pemetrexed
500 mg/m2 IV given over 10 minutes every 21 days
Other Name: Alimta
Drug: Bevacizumab
15 mg/kg IV every 21 days
Other Name: Avastin
Drug: Carboplatin
AUC=5 IV every 21 days
Other Name: Paraplatin
Experimental: Pemetrexed
Pemetrexed 500 mg/m2 IV given over 10 minutes every 21 days
Drug: Pemetrexed
500 mg/m2 IV given over 10 minutes every 21 days
Other Name: Alimta

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00892710

  Show 27 Study Locations
Sponsors and Collaborators
SCRI Development Innovations, LLC
Genentech
Investigators
Study Chair: Rogerio C Lilenbaum, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00892710     History of Changes
Other Study ID Numbers: SCRI LUN 196
Study First Received: April 30, 2009
Last Updated: May 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Non small cell lung cancer
NSCLC
NSCLC IIB/IV
Pemetrexed
Bevacizumab
Avastin
Carboplatin
Stage IIIB/IV

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Bevacizumab
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014