Carboplatin and Gemcitabine With Bevacizumab Every 2 Weeks for Stage IIIb/IV Non-small Cell Lung Cancer

NCT00400803 | Completed Phase 2 Results DMC

• 4 other identifiers: 2007UC021HHH2L06AVF3982sB9E-US-X463
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether treatment with carboplatin and gemcitabine combined with bevacizumab every two weeks will provide increased survival.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Carcinoma, Non-Small-Cell Lung; Gemcitabine; Carboplatin; Bevacizumab; Biological therapy; Drug therapy

Outcome Measures

Primary Outcomes (1)

• Time to Progression

  Time to progression (progression free survival)is defined as the time from the start of treatment until first documented sign of disease progression or death due to any cause. For subjects who do not progress, time to progression will be censored at the time of last tumor assessment.

  From Enrollment Through 2 Years

Secondary Outcomes (4)

• Best Overall Response by Cycle

  After Cycle 4, Cycle 6 and Cycle 7 of Therapy

• Duration of Response

  From Enrollment through Date of First Documented Disease Progression or Date of Death From Any Cause, Whichever Came First, Up to 100 Months

• Overall Survival Time

  Baseline to Death

• Time to Best Response

  From Enrollment to First Tumor Response

Study Arms (1)

Patients with Stage IIIb/IV Non-Small Cell Lung Cancer

EXPERIMENTAL

Patients treated with Gemcitabine 2000mg/m\^2 intravenously (IV) over 30 minutes, followed by Carboplatin AUC= 3 IV over 30 minutes and Bevacizumab 10 mg/kg IV over 90 minutes 1st infusion, 60 minutes 2nd infusion and 30 minutes for the following infusions. Cycles will be repeated every 2 weeks for a maximum of 6 cycles of therapy. Bevacizumab will continue to be given until disease progression.

Drug: Gemcitabine, Carboplatin, Bevacizumab

Interventions

Gemcitabine, Carboplatin, Bevacizumab DRUG

Patients will be treated with Gemcitabine 2000mg/m\^2 intravenously (IV) over 30 minutes, followed by Carboplatin AUC= 3 IV over 30 minutes and Bevacizumab 10 mg/kg IV over 90 minutes 1st infusion, 60 minutes 2nd infusion and 30 minutes for the following infusions. Cycles will be repeated every 2 weeks for a maximum of 6 cycles of therapy. Bevacizumab will continue to be given until disease progression.

Also known as: Gemzar, Carboplatin, Avastin

Patients with Stage IIIb/IV Non-Small Cell Lung Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) EXCEPT squamous cell carcinoma or predominantly squamous. Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible. (Sputum cytology alone is not acceptable)
• Must have disease that is not curative by standard methods.
• Prior adjuvant systemic chemotherapy, immunotherapy, or biological therapy is allowed, except for prior use of bevacizumab. If gemcitabine was used, more than six months must have elapsed between completion of adjuvant therapy and disease progression. Patient must be at least 14 days from previous systemic therapy (at least 30 days for investigational agents) and have recovered from the acute toxic effects of the treatment as determined by the treating physician prior to study registration. Prior therapy other than adjuvant therapy is not allowed.
• Prior radiation therapy must be completed at least 14 days of study registration and subjects must fully recover from acute toxicities as determined by the treating physician. Prior radiation to \> 25% of bone marrow is not allowed. Prior radiation therapy to the whole pelvis is not allowed.
• Disease status must be measurable or non-measurable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• ECOG Performance status of 0 or 1
• Age 18 years or greater
• Adequate organ function within 14 days of study registration including the following:
• Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelets ≥ 100 x 10\^9/L, hemoglobin ≥ 9 g/dL
• Hepatic: bilirubin ≤ 1.5 times the upper limit of normal (× ULN), alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × ULN (ALP, AST, and ALT ≤ 5 × ULN is acceptable if liver has tumor involvement)
• Renal: Adequate renal function as evidenced by creatinine clearance of \> 50ml/min, estimated by the Cockcroft-Gault equation 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 ≤ 1g of protein in 24 hours to be eligible)
• Coagulation: INR \< 1.5, PTT \< the upper limits of normal (ULN) unless stable on therapeutic anticoagulation at study entry. The addition of anticoagulants after study start is not allowed.
• Women of childbearing potential and sexually active males are required to use an effective method of contraception (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicidal, condom with spermicidal, or abstinence) during the study and for 3 months after the last dose of study drug.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

You may not qualify if:

• Pregnant (positive pregnancy test within 14 days of study enrollment) or breast-feeding. Gemcitabine and carboplatin are pregnancy category D - clear evidence of risk in pregnancy; bevacizumab is pregnancy category C - risk in pregnancy cannot be ruled out. Pregnancy testing is not required for post-menopausal (defined as absence of menses for the preceding 24 consecutive months) or surgically sterilized women.
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Clinically significant peripheral vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy in the absence of therapeutic anticoagulation
• Current or recent (within 10 days of enrollment) use of aspirin (\>325 mg/day) or chronic use of other NSAIDs known to inhibit platelet function Treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal)
• Requiring therapeutic anticoagulation
• Current, ongoing treatment with full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin)
• History of thrombotic or hemorrhagic disorders
• T4 tumors with invasion of the heart or great vessels
• Presence or history of central nervous system or brain metastases, except for treated brain metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI/CT) during the screening period. Anticonvulsants are allowed, providing the subject is on a stable dose. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Subjects with CNS metastases treated by radiotherapy within 28 days of Day 1 will be excluded. Subjects treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
• History of another malignancy other than NSCLC except in situ carcinoma of the cervix; adequately treated nonmelanomatous carcinoma of the skin; low grade (Gleason score ≤ 6) localized prostate cancer or other prior malignancy treated at least 2 years previously with no evidence of recurrence

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Hubert H. Humphrey Cancer Center

Minneapolis, Minnesota, 55422, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• Dudek AZ, Kumar P, H Thaw SS, Cao Q, Pawloski P, Larson T. Phase II study of biweekly carboplatin, gemcitabine, and bevacizumab as first-line treatment in patients with stage IIIB/IV NSCLC. Am J Clin Oncol. 2014 Apr;37(2):140-3. doi: 10.1097/COC.0b013e31826b9e12.

  PMID: 23111363 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gemcitabine; Carboplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Outcome data is available for 35 (of 38) patients only.

Results Point of Contact

• Title: Arkadiusz Dudek, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

dudek002@umn.edu

612-624-0123

Study Officials

• Priya Kumar, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2006
• First Posted: November 17, 2006
• Study Start: March 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: December 28, 2017
• Results First Posted: January 26, 2012

Record last verified: 2017-12

Locations

US (2)