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

NCT01700400 | Completed Phase 1

• 1 other identifier: CRAB CTC 10-001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer

Keywords

Lung Cancer; Non Small Cell Lung Cancer; Advanced Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Define the Maximum Tolerated Dose (MTD) and Recommended Phase Two Dose (RPTD) of the combination of everolimus with pemetrexed, carboplatin, and bevacizumab in patients with Stage IV non-squamous NSCLC.

  Pemetrexed, carboplatin and bevacizumab will be given intravenously on day 1 of a 21-day cycle with doses determined by the dose level to which the patient is assigned. Everolimus will be taken orally days 1-21 of a 21-day cycle. There will be no rest between each 21 day cycle. Tumor scans will be done every 2 treatment cycles. Patients who are not progressing and who are tolerating therapy will be treated with 6 cycles of Pem/Carbo/Bev/Everolimus followed by maintenance Pem/Bev/Everolimus, which will be continued if there is no tumor progression and the patient is tolerating therapy. If there is toxicity related specifically to one of the maintenance drugs, that drug will be discontinued and the other drugs will be maintained.

  up to 2 years

Secondary Outcomes (4)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  up to 2 years

• Antitumor efficacy associated with administration of everolimus/pemetrexed/carboplatin/bevacizumab administration in patients with Stage IV non-squamous NSCLC.

  up to 2 years

• Progression-free survival (PFS)

  up to 2 years

• Overall Survival (OS)

  up to 2 years

Study Arms (1)

Experimental Phase I Dose Escalation

EXPERIMENTAL

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

Drug: Everolimus; Drug: Pemetrexed; Drug: Carboplatin; Drug: Bevacizumab

Interventions

Everolimus DRUG

Also known as: Afinitor, Zortress, RAD001

Experimental Phase I Dose Escalation

Pemetrexed DRUG

Also known as: Alimta

Experimental Phase I Dose Escalation

Carboplatin DRUG

Also known as: Paraplatin, CBDCA

Experimental Phase I Dose Escalation

Bevacizumab DRUG

Also known as: Avastin

Experimental Phase I Dose Escalation

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Confirmed diagnosis of Stage IV non-squamous non-small cell lung cancer
• 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.
• 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.
• Age ≥ 18 years
• Normal blood function levels as evidenced by laboratory tests.
• Adequate liver, kidney and blood chemistry function.
• Adequate blood clotting levels
• Urine dipstick levels of protein must be between 0-1+.
• 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.
• The ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.
• 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.

You may not qualify if:

• 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
• Clinically significant cardiac event such as Myocardial infarction
• Inadequately controlled high blood pressure
• 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
• Presence of fluid accumulation which cannot be controlled by drainage
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment
• History of stroke within 6 months prior to enrollment
• History of significant vascular disease within 6 months prior to enrollment(i.e., aortic aneurysm)
• No unusual bleeding or inability to clot (assuming not on anti-coagulation); patients with a history of DVT and/pr pulmonary embolism are excluded
• Serious non-healing wound, ulcer, or bone fracture
• 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.
• Untreated brain metastases Radiation treatment than 28 days prior to registration. Side effects due to radiation therapy must have resolved.
• Coughing up of blood
• Excessive protein in your urine
• Abnormal levels of lipids in your blood

Sponsors & Collaborators

• Cancer Research and Biostatistics Clinical Trials Consortium: lead
• University of Arizona: collaborator
• Providence Cancer Center, Earle A. Chiles Research Institute: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (4)

University of Arizona Cancer Center

Tuscon, Arizona, 85724, United States

Location

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Cancer Research And Biostatistics Clinical Trials Consortium

Seattle, Washington, 98101, United States

Location

Related Links

• Providence Cancer Center of Portland, Oregon

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Everolimus; Pemetrexed; Carboplatin; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Linda L. Garland, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

• John Crowley, PhD

  Cancer Research And Bioststistics

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: October 4, 2012
• Study Start: September 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: November 24, 2014

Record last verified: 2014-05

Locations

US (4)