Carboplatin, Bevacizumab and Pemetrexed in Advanced Non Small Cell Lung Cancer (H3E-US-X072)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Christiana Care Health Services
ClinicalTrials.gov Identifier:
NCT00614822
First received: January 30, 2008
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to look for an improvement in progression free survival with the combination of bevacizumab, carboplatin and pemetrexed in patients with newly diagnosed advanced/metastatic non small cell lung cancer. Overall survival and safety will also be assessed.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Carboplatin, Bevacizumab and Pemetrexed in Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Christiana Care Health Services:

Primary Outcome Measures:
  • efficacy of a novel combination of Carboplatin, Pemetrexed and Bevacizumab used concurrently in the treatment of NSCLC [ Time Frame: CT scans to determine evaluation of response after 2 cycles of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • assessment of treatment tolerability measured by adverse events such as grade 4 toxicities, hospitalizations for toxicities, fever and neutropenia events and clinically significant bleeding/thrombotic events [ Time Frame: will document all adverse experiences after the start of the study and will follow up subjects until event has disappeared or condition stabilized ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: November 2007
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
one arm for study
Carboplatin, Pemetrexed and Bevacizumab are given day 1 every 3 weeks for 6 cycles and will be continued if patient tolerates treatments and has stable disease. The Bevacizumab will be continued every 3 weeks for 1 year if the patient tolerates treatment and has stable disease.
Drug: Carboplatin, Pemetrexed and Bevacizumab
Carboplatin AUC 5 IV day 1 over 30-60 minutes Pemetrexed 500 mg/M2 IV day 1 over 10 minutes Bevacizumab 15 mg /kg IV day over 90 minutes dose 1, 60 minutes dose 2, 30 minutes subsequent doses. Repeat every 3 weeks for total of 6 cycles
Other Names:
  • Paraplatin
  • Alimta
  • Avastin

Detailed Description:

Carboplatin: AUC 5 IV over 30-60 minutes on day 1 Pemetrexed: 500mg/M2 IV over 10 minutes on day 1 Bevacizumab: 15mg/kg IV over 90 minutes on day 1 (if rate is tolerated the 2nd dose may be decreased to 60 minutes and subsequent doses to 30 minutes This regimen will be administered every 6 weeks for up to a maximum of 6 cycles if the patient tolerates the treatment and has stable disease. Bevacizumab will be continues if tolerated for up to 1 year at every 3 week intervals.

Folic acid 1mg by mouth daily, Vitamin B12 1000 ug IM every 9 weeks and Dexamethasone 4mg by mouth twice a day and and antiemetic may be prescribed by the physician investigator to help reduce side effects associated with the Pemetrexed. The Folic acid and Vitamin B12 will continue until 3 weeks after the end of treatment.

Physical exams, vital signs and blood work will be done prior to each chemotherapy cycle. A urine dipstick to check for protein in the urine will be done prior to the first treatment and before cycles 3 and 5. A CAT scan of the chest will be done pretreatment, prior to cycles 3 and 5 and at the end of treatment.

  Eligibility

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

Inclusion Criteria:

  • Advanced stage NSCLC (IIIB with malignant pleural effusion; T4 [on basis on satellite lesion] N2, 3; or stage IV) excluding squamous cell histology, with measurable or evaluable disease.
  • Prior chemotherapy therapy for early stage disease with one regimen is acceptable if it was completed at least 6 months prior to study entry.
  • Palliative radiotherapy to painful bony metastases will be permitted prior to study entry if completed prior to initiation of study treatment, and there are no residual sequelae of therapy such as bone marrow suppression.
  • Life expectancy of at least 3 months.
  • ECOG Performance status 0-1.
  • Age 18 or higher.
  • Willingness to use appropriate contraception to avoid pregnancy during the study (female patient or female partner of a male patient)
  • Patients must have normal organ and marrow function as defined below:

leukocytes greater than or equal to3,000/µl ANC greater than or equal to 1,500/µl platelets greater than or equal to 100,000/µl total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance ≥ 45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

  • Ability to sign informed consent
  • Ability to take folic acid, Vitamin B12 and dexamethasone as per protocol
  • Ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Alimta.

Exclusion criteria

Patients meeting any of the following criteria are ineligible for study entry:

  • Prior cytotoxic treatment for advanced NSCLC. One prior regimen (up to 4 cycles) of neoadjuvant or adjuvant therapy for early stage disease will be allowed if completed at least 6 months prior to study entry.
  • Prior definitive chest irradiation (radiation of rib or spine mets permitted)
  • Known brain metastases (unless previously resected and radiated)
  • Prior treatment with bevacizumab or pemetrexed
  • History of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to bevacizumab or carboplatin
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study.
  • Concomitant chemotherapy, radiotherapy or investigational agents.
  • Evidence of bleeding diathesis or coagulopathy.
  • Use of anti-coagulant agents warfarin (1mg, by mouth, daily for port maintenance permitted), heparin (ASA, NSAID permitted).
  • Pregnant (positive pregnancy test) or lactating women.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study.
  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0.
  • Urine protein creatinine ratio 1.0 at screening. -History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to Day 0.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, or with significant cavitation as assessed by treating investigator in consultation with an attending radiologist. -Recent history of hemoptysis (bright red blood of 1/2 teaspoon or more)- within one month of study entry
  • Significant co-morbidities including:

Blood pressure of 150/100 mmHg Unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix B) History of myocardial infarction within 6 months History of stroke within 6 months Clinically significant peripheral vascular disease

  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Another active malignancy except for non-melanoma skin cancers.
  • Clinically significant pleural, pericardial, and/or peritoneal effusions unless drained or controlled prior to study entry.
  • Undrainable, clinically relevant effusions and presence of third space fluid which cannot be controlled by drainage.
  • Hepatic impairment as evidenced by Bilirubin greater than 1.5 times the upper limit of normal Transaminases greater than 3.0 times limit of normal (ULN), except in presence of known hepatic metastasis, wherein may be up to 5 times ULN
  • Any CTCAE Version 3.0 Grade 3 or 4 non hematologic toxicity
  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: NCT00614822

Sponsors and Collaborators
Christiana Care Health Services
Eli Lilly and Company
Investigators
Principal Investigator: Michael Guarino, MD Christiana Care Health Services
  More Information

No publications provided

Responsible Party: Christiana Care Health Services
ClinicalTrials.gov Identifier: NCT00614822     History of Changes
Other Study ID Numbers: 24091, Eli Lilly H3E-US-X072
Study First Received: January 30, 2008
Last Updated: August 5, 2014
Health Authority: United States: Institutional Review Board

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
Bevacizumab
Pemetrexed
Carboplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 22, 2014