Clinical trial NCT02151149: Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
Official title: Safety and Efficacy of Nab-paclitaxel (Abraxane) in Combination With Carboplatin as First Line Treatment in Elderly Subjects With Advance Non-Small Cell Lung Cancer (NSCLC): A Phase IV, Randomized, Open-Label, Multicenter Study (Abound.70+)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non-Small Cell Lung Cancer
Carcinoma
Squamous Cell Carcinoma
Adenocarcinoma
Carcinoma, Large Cell
Lung Neoplasm
Keywords: NSCLC advanced non-small cell lung cancer squamous adenocarcinoma large cell carcinoma lung cancer elderly first line treatment abraxane carbo nab-paclitaxel
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-05-30
Enrollment: 143
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study comparing two regimens of nab-paclitaxel and carboplatin combination in elderly subjects (≥ 70 years old) with advanced NSCLC

Detailed description: This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus weekly times three with one-week break nab-paclitaxel in combination with carboplatin as first-line treatment in elderly subjects (≥ 70 years old) with advanced non small cell lung cancer who have not received prior chemotherapy for their advanced disease and are not candidates for curative surgery or radiation therapy. The primary study endpoint is the percentage of subjects with either peripheral neuropathy or myelosuppression adverse events. Patients will continue treatment until they develop progressive disease, unacceptable side-effects or wish to withdraw from the study, according to local standard of care. Patients will have radiographic evaluations every 6 weeks while on treatment.

Eligibility criteria: Inclusion Criteria: -

* Inclusion Criteria: -

  1. Age ≥ 70 years at the time of signing the Informed Consent Form.
  2. Understand and voluntarily provide written informed consent prior to the conduct of any study related assessments/procedures.
  3. Able to adhere to the study visit schedule and other protocol requirements.
  4. Histologically or cytologically confirmed locally advanced or metastatic non small cell lung cancer who are not candidates for curative surgery or radiation therapy.
  5. No other current active malignancy requiring anticancer therapy.
  6. Radiographically documented measurable disease per RECIST v 1.1
  7. No prior chemotherapy for the treatment of metastatic disease. Adjuvant chemotherapy is permitted providing that cytotoxic chemotherapy was completed 12 months prior to signing the informed consent form (ICF) and without disease recurrence. Participans with previously known epidermal growth factor receptor mutation or anaplastic lymphoma kinase gene translocation must have failed or had intolerance to one treatment with epidermal growth factor receptor tyrosine kinase inhibitor or anaplastic lymphoma kinase inhibitor therapy, respectively.
  8. Absolute neutrophil count ≥ 1500 cells/cubic millimetre.
  9. Platelets ≥ 100,000 cells/cubic millimetre.
  10. Hemoglobin ≥ 9 grams/decilitre.
  11. Aspartate transaminase/serum glutamic oxaloacetic transaminase/ alanine transaminase/serum glutamic pyruvic transaminase ≤ 2.5 × upper limit of normal range or ≤ 5.0 × upper limit of normal range if liver metastases.
  12. Total bilirubin ≤ 1.5 millilitre/decilitre (unless there is a known history of Gilberts Syndrome).
  13. Creatinine clearance \> 40 millilitre/minute calculated using Cockcroft-Gault equation (if renal impairment is suspected 24 hour urine collection for measurement is required).
  14. Eastern Cooperative Oncology Group performance status 0 or 1.
  15. Females who (1) have undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have been naturally postmenopausal for at least 24 consecutive months (ie, has not had menses at any time during the preceding 24 consecutive months).
  16. Male subjects must: Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following study drug discontinuation, even if he has undergone a successful vasectomy.

      Exclusion Criteria:
* 1. Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for ≥ 4 weeks prior to signing Informed consent form. Magnetic Resonance Imaging of the brain (or Computed Tomography scan w/contrast) is preferred for diagnosis.

  2. History of leptomeningeal disease. 3. Only evidence of disease is non measurable. 4. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria for Adverse Events v4.0).

  5. Participant has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting investigational product, and/or from whom ≥ 30% of the bone marrow was irradiated. Prior radiation therapy to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.

  6. Venous thromboembolism within 1 month prior to signing informed consent form.

  7. Current congestive heart failure (New York Heart Association Class II-IV). 8. History of the following within 6 months prior to first administration of a study drug: a myocardial infarction, severe/unstable angina pectoris,coronary/peripheral artery bypass graft, New York Heart Association Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant Electrocardiogram abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.

  9. Participant has a known infection with hepatitis B or C, or history of human immunodeficiency virus infection, or participant is receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications.

  10. Participant has an active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.

  11.History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis.

  12. Treatment with any investigational product within 28 days prior to signing the informed consent form.

  13. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin. 14. Currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices. 15. Any other clinically significant medical condition, psychiatric illness, and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol or which, in the views of investigator, preclude combination chemotherapy.

  16. Participant has any other malignancy within 5 years prior to randomization. Exceptions include the following: squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer Tumor, Lymph Node, Metastatic (TNM stage of T1a or T1b). All treatment of which should have been completed 6 months prior to signing Informed consent form.

  17. Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.

  18. Any medical condition that confounds the ability to interpret data from the study.

  19. Females who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months).

Primary outcomes:
measure: Percentage of Participants With Either Peripheral Neuropathy ≥ Grade 2 or Myelosuppression Adverse Events (AEs) ≥ Grade 3 Based on Local Laboratory Values
timeFrame: From the date of the first dose of investigational product (IP) until 28 days after the last dose of IP; up to data cut-off date of 20 November 2016; The median treatment duration for Arms A and B were 3.04 months and 5.17 months respectively.
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events During the Treatment Period
timeFrame: From the date of the first dose of IP until 28 days after the last dose of IP; up to a later data cut-off date of 14 July 2017; maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively.
measure: Percentage of Participants With at Least 1 Treatment Emergent Adverse Event With Action Taken as Study Drug Withdrawn
timeFrame: From the date of the first dose of IP until 28 days after the last dose of IP; up to a later data cut-off date of 14 July 2017 the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively
measure: Dose Intensity Per Week of Nab-Paclitaxel During the Entire Study
timeFrame: From day 1 of study treatment to the end date of study treatment; up to data cut off date of 20 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively
measure: Dose Intensity Per Week of Carboplatin During the Entire Study
timeFrame: From day 1 of study treatment to the end date of study treatment; up to data cut off date of 20 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively
measure: Percentage of Participants With Dose Reductions During the Entire Study
timeFrame: From the first dose of study treatment to discontinuation date of study treatment; up to date cut off date of 20 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively
measure: Percentage of Participants With a Dose Delay During the Entire Study
timeFrame: From the first dose of study treatment to discontinuation date of study treatment; up to date cut off date of 16 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively
measure: Kaplan Meier Estimate of Progression-Free Survival (PFS)
timeFrame: From first dose of IP to the date of disease progression; up to a later clinical cut-off date of 14 July 2017; for Arms A and B participants were followed for PFS for 31 months and 20 months respectively
measure: Kaplan Meier Estimate of Overall Survival (OS)
timeFrame: From first dose of IP to the date of death due to any cause; up to a later clinical cut-off date of 14 July 2017; for Arms A and B participants were followed for OS for 31 months and 33 months respectively
measure: Percentage of Participants Who Achieved a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST 1.1 Criteria
timeFrame: From the first dose of IP to the date of documented first response; up to the data cut-off date of 14 July 2017; maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Hot Springs
country: United States
facility: Genesis Cancer Center
state: Arkansas
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fullerton
country: United States
facility: Saint Jude Heritage Medical Center
state: California
city: Gilroy
country: United States
facility: Global Cancer Research Institute (GCRI), Inc.
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Grand Junction
country: United States
facility: St Mary's Hospital and Regional Medical Center
state: Colorado
city: Boca Raton
country: United States
facility: Lynn Cancer Institute
state: Florida
city: Jacksonville
country: United States
facility: Baptist Cancer Inst
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Evanston
country: United States
facility: Northshore University Healthsystem Research Institute
state: Illinois
city: Niles
country: United States
facility: Oncology Specialists, S.C.
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Paducah
country: United States
facility: Western Kentucky Hematology and Oncology Group
state: Kentucky
city: Marrero
country: United States
facility: West Jeffersion Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Institutions
state: Louisiana
city: Baltimore
country: United States
facility: Medstar Health Research Institute
state: Maryland
city: Worcester
country: United States
facility: Reliant Medical Group
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Cherry Hill
country: United States
facility: Center for Cancer and Hematologic Disease
state: New Jersey
city: East Brunswick
country: United States
facility: Regional Cancer Care Associates LLC
state: New Jersey
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Carol G Simon Cancer Center
state: New Jersey
city: Somerville
country: United States
facility: Somerset Hematology-Oncology Associates
state: New Jersey
city: Sparta
country: United States
facility: Regional Cancer Care Associates LLC- Sparta division
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: Brookdale University Hospital and Medical Center
state: New York
city: Johnson City
country: United States
facility: Broome Oncology, LLC
state: New York
city: Lake Success
country: United States
facility: Clinical Research Alliance
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Medicine Oncology
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Memorial Hospital, Inc.
state: North Carolina
city: Youngstown
country: United States
facility: St Elizabeth Hospital
state: Ohio
city: Lawton
country: United States
facility: Cancer Centres of Southwest Okahoma Research
state: Oklahoma
city: Corvallis
country: United States
facility: Good Samaritan Hospital Corvalis
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Medical College
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Amarillo
country: United States
facility: Texas Oncology, P.A.-Amarillo
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center at Dallas
state: Texas
city: Galveston
country: United States
facility: UTMB Galveston
state: Texas
city: Longview
country: United States
facility: Texas Oncology, PA - Longview
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Cancer Center
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
Study officials:
affiliation: Celgene
name: Teng Jin Ong
role: STUDY_DIRECTOR
References: