Study of Everolimus, Pemetrexed, Carboplatin, and Bevacizumab to Treat Stage IV Lung Cancer

NCT ID: NCT01700400

Last Updated: 2014-11-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2014-10-31

Brief Summary

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The purpose of this study is to determine whether the investigational study drug everolimus may be used to increase the effectiveness of chemotherapy treatment for patients with advanced lung cancer.

Detailed Description

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Advanced lung cancer remains an incurable disease although new agents and new treatment strategies have resulted in improved survival outcomes for patients. Most recently there has been interest in augmenting tumor response to chemotherapy by the addition of drugs which inhibit tumor cell growth and proliferation. Everolimus is a new cancer drug which works as an inhibitor of mammalian target of rapamycin (or mTOR), mTOR is a protein that is part of a signaling pathway which can cause cancer cells to divide. Everolimus when used alone as a single agent has produced some response as well as prolonged stable disease in both chemo-naïve and pre-treated non-small cell lung cancer. The goal of this study is to evaluate the safety of everolimus with combined other cancer drugs called pemetrexed, carboplatin, and bevacizumab. Pemetrexed and carboplatin are both chemotherapy drugs and bevacizumab inhibits the growth of new blood vessels.

Patients will be entered onto dosing cohorts of 3 patients according to the following dose escalation scheme. The first cohort will begin at dose level 1. At least three patients on each dose level must have completed cycle one before the study leadership (principal investigators, study statisticians) will allow patients to be enrolled onto the successive dose level.

Dose Levels: 1, 2, 3

Pemetrexed (mg/m²): 500, 500, 500

Carboplatin (AUC): 5, 6, 6

Bevacizumab (mg/kg): 15, 15, 15

Everolimus (mg/day): 2.5, 2.5, 5.0

The purpose of this study is to determine the maximum tolerated dose, or MTD, for the combination of everolimus with pemetrexed, carboplatin, and bevacizumab in patients with Stage IV non-squamous, non small cell lung cancer.

Conditions

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Non Small Cell Lung Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Experimental Phase I Dose Escalation

Pemetrexed: intravenous; 500 mg/m² for Dose Levels 1, 2 and 3

Carboplatin: intravenous; 5 AUC for Dose Level 1; 6 AUC for Dose Levels 2 and 3

Bevacizumab: intravenous; 15 mg/kg for Dose Levels 1, 2, and 3

Everolimus: oral, 2.5 mg/day for Dose Levels 1 and 2; 5.0 mg/day for Dose Level 3

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

Pemetrexed

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Bevacizumab

Intervention Type DRUG

Interventions

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Everolimus

Intervention Type DRUG

Pemetrexed

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Bevacizumab

Intervention Type DRUG

Other Intervention Names

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Afinitor Zortress RAD001 Alimta Paraplatin CBDCA Avastin

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent
2. Confirmed diagnosis of Stage IV non-squamous non-small cell lung cancer
3. CT of the chest, abdomen, and pelvis which shows metastatic disease. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
4. At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
5. Age ≥ 18 years
6. Normal blood function levels as evidenced by laboratory tests.
7. Adequate liver, kidney and blood chemistry function.
8. Adequate blood clotting levels
9. Urine dipstick levels of protein must be between 0-1+.
10. Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x IULN. Testing must be performed within 14 days prior to enrollment.
11. The ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.
12. No prior treatment with everolimus. Prior treatment with pemetrexed or carboplatin is allowed, provided no disease progression with prior exposure to drugs. Prior treatment with bevacizumab allowed.

Exclusion Criteria

1. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
2. Clinically significant cardiac event such as Myocardial infarction
3. Inadequately controlled high blood pressure
4. Active gastrointestinal disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for IVplacement; prior surgical procedures affecting absorption; or active peptic ulcer disease
5. Presence of fluid accumulation which cannot be controlled by drainage
6. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment
7. History of stroke within 6 months prior to enrollment
8. History of significant vascular disease within 6 months prior to enrollment(i.e., aortic aneurysm)
9. No unusual bleeding or inability to clot (assuming not on anti-coagulation); patients with a history of DVT and/pr pulmonary embolism are excluded
10. Serious non-healing wound, ulcer, or bone fracture
11. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1.
12. Untreated brain metastases Radiation treatment than 28 days prior to registration. Side effects due to radiation therapy must have resolved.
13. Coughing up of blood
14. Excessive protein in your urine
15. Abnormal levels of lipids in your blood
16. Previous or current malignancies within the last 3 years, with the exception of cervical cancer and adequately treated basal cell or squamous cell carcinoma of the skin
17. Prior treatment with any investigational drug within the preceding 4 weeks prior to enrollment
18. Patients receiving chronic, systemic treatment with corticosteroids or another immunotherapy. Topical or inhaled corticosteroids are allowed.
19. Patients must not receive immunization with attenuated live vaccines within one week prior to study enrollment or during study period.
20. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation.
21. HIV positive
22. Impairment of stomach or intestinal function or stomach or intestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
23. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus.
24. Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
25. Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Arizona

OTHER

Sponsor Role collaborator

Providence Cancer Center, Earle A. Chiles Research Institute

OTHER

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Cancer Research and Biostatistics Clinical Trials Consortium

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Linda L. Garland, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

John Crowley, PhD

Role: STUDY_CHAIR

Cancer Research And Bioststistics

Locations

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University of Arizona Cancer Center

Tuscon, Arizona, United States

Site Status

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Providence Cancer Center

Portland, Oregon, United States

Site Status

Cancer Research And Biostatistics Clinical Trials Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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CRAB CTC 10-001

Identifier Type: -

Identifier Source: org_study_id