Pemetrexed, Carboplatin, and Bevacizumab as First-Line Therapy in Treating Older Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Alliance for Clinical Trials in Oncology

Status and phase

Completed

Phase 2

Conditions

Lung Cancer

Treatments

Drug: carboplatin

Drug: pemetrexed disodium

Biological: bevacizumab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00798603

CDR0000626346 (Registry Identifier)

NCI-2009-00670 (Registry Identifier)

NCCTG-N0821

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving pemetrexed together with carboplatin and bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving pemetrexed together with carboplatin and bevacizumab works as first-line therapy in treating older patients with stage IIIB or stage IV non-small cell lung cancer.

Full description

OBJECTIVES:

Primary

To estimate the progression-free survival at 6 months in elderly patients with advanced nonsquamous cell non-small cell lung cancer treated with pemetrexed disodium, carboplatin, and bevacizumab as first-line therapy.

Secondary

To assess the adverse events profile and safety of this regimen in these patients.
To estimate the confirmed antitumor response rate, as defined by RECIST criteria, and the overall survival of these patients.
To compare the quality of life (QOL) of patients treated with this regimen vs the QOL of younger patients.
To correlate QOL with toxicities, as defined by NCI CTCAE v3.0 criteria.

Tertiary

To evaluate polymorphisms in the genes that encode proteins involved in the cellular transport, activation, and cytotoxic activity of pemetrexed disodium and evaluate their relationship with treatment toxicity/efficacy and patient QOL.
To evaluate polymorphisms in the genes involved in blood pressure regulation and their relationship with susceptibility to hypertension induced by anti-VEGF therapy.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response after 6 courses may continue to receive pemetrexed disodium and bevacizumab every 21 days in the absence of disease progression or unacceptable toxicity.

Tissue and blood samples are collected at baseline for pharmacogenetic analysis. Blood samples are used to evaluate functionally relevant polymorphisms in the genes that encode proteins involved in the transport and activation of pemetrexed disodium and in the genes that encode proteins involved in susceptibility to hypertension induced by bevacizumab. Tissue samples are used to evaluate expression and polymorphisms in pemetrexed disodium target genes (TS, DHFR, and GARFT).

Quality of life is assessed at baseline and periodically during study.

After completion of study therapy, patients are followed periodically for up to 5 years.

Enrollment

65 patients

Sex

All

Ages

70 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed nonsquamous cell non-small cell lung cancer (NSCLC)
- Stage IIIB (with pleural effusion) or IV disease
- Squamous cell carcinomas not allowed
  - Adenosquamous histology allowed
Clinically significant effusion (e.g., symptomatic pleural effusion or ascites) allowed provided it is drained before study treatment
- No symptomatic pleural and/or peritoneal effusion (≥ grade 2 dyspnea, as defined by NCI CTCAE v3.0 criteria) that is not amenable to drainage
- If effusion produces clinically significant measurable objective changes, such as hypoxia or estimated volume > 500 mL, effusion should be drained even if asymptomatic
Measurable disease, defined as ≥ 1 lesion with longest diameter ≥ 2.0 cm by conventional techniques or ≥ 1.0 cm by spiral CT scan
- If the sole site of disease is in a previously irradiated field, must have evidence of disease progression/recurrence within the irradiated field OR presence of a new lesion outside the irradiated field
No symptomatic, untreated, or uncontrolled CNS metastases
- CNS metastases that were previously treated with whole brain radiotherapy (WBRT) allowed
Willing to enroll in NCCTG-N0392

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy ≥ 12 weeks
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal
AST and ALT ≤ 3 times ULN (≤ 5 times ULN if liver has tumor involvement)
Creatinine clearance ≥ 45 mL/min
Not pregnant or nursing
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
Able to take folic acid, vitamin B_12 supplementation, or dexamethasone
Able to complete questionnaire(s) alone or with assistance
Willing to provide biologic specimens as required by the study
Willing to return to NCCTG participating center for follow-up
No clinically significant infection
No serious, nonhealing wounds, ulcers, or bone fractures
No seizure disorder
No second primary malignancy within the past 5 years, except for any of the following:
- Carcinoma in situ of the cervix
- Nonmelanomatous skin cancer
  - History of melanoma allowed only if diagnosed and definitively treated ≥ 5 years ago with no subsequent evidence of recurrence
- Low-grade (Gleason score ≤ 6) localized prostate cancer (no nodal involvement)
- Previously treated stage I breast cancer
No concurrent severe and/or uncontrolled medical condition, including any of the following:
- Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication
- Angina pectoris
- Congestive heart failure within the past 3 months, unless ejection fraction > 40%
- Myocardial infarction within the past 6 months
- Cardiac arrhythmia
- Diabetes mellitus
- Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the lung
- Active or recent history of hemoptysis > ½ teaspoon per event
- Ongoing or active infection
- Psychiatric illness/social situation that would limit compliance with study requirements
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 12 months
No diverticulitis within the past 12 months
No stroke within the past 6 months
No significant traumatic injury within the past 8 weeks
Not at greater than normal risk of bleeding

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior radiotherapy to > 25% of bone marrow
More than 2 weeks since prior radiotherapy and recovered (alopecia allowed)
At least 2 weeks since prior WBRT
At least 3 days since prior gamma knife radiosurgery (without WBRT) for brain metastases
More than 4 weeks since prior administration of live or attenuated viral vaccine
More than 8 weeks since prior major surgery (e.g., laparotomy) or open biopsy (> 4 weeks since minor surgery)
- Insertion of a vascular access device allowed
No prior chemotherapy or systemic therapy for advanced lung cancer, except neoadjuvant or adjuvant chemotherapy
No NSAID's 2 days prior to (5 days for long-acting NSAID's), the day of, and 2 days following protocol treatment
More than 12 months since prior neoadjuvant therapy, adjuvant therapy, systemic chemotherapy, chemoradiotherapy, immunotherapy, or biologic therapy
No concurrent anticoagulants
- Low-dose warfarin or heparin for deep venous thrombosis prophylaxis allowed