Safety and Efficacy Study of Abraxane as Maintenance Treatment After Abraxane Plus Carboplatin in 1st Line Stage IIIB / IV Squamous Cell Non-small Cell Lung Cancer
Condition: Squamous Cell Carcinoma, Non-Small-Cell Lung
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Abraxane (Induction); Carboplatin (Induction); Abraxane (Maintenance); Best Supportive Care (Maintenance); Abraxane (Induction); Carboplatin (Induction); Best Supportive Care (Maintenance)
Intervention description: 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 15 of each 21-day cycle, administered as standard of care; 6 mg/min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion; 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day cycle, administered as standard of care; The best palliative care per investigator (including but not limited to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding antineoplastic agents; 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and 15 of each 21-day cycle, administered as standard of care; 6 mg/min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion, administered as standard of care; The best palliative care per investigator (including but not limited to: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and/or focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis), excluding antineoplastic agents
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 427.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Nab-paclitaxel; Albumin bound paclitaxel; Taxanes; Maintenance trials; Celgene; Abraxane; ABI-007; NSCLC; Non-Small Cell Lung Cancer; Cancer of the Lung; Carcinoma, Squamous Cell; Lung Neoplasms; Abound.sqm

Summary:

      Maintenance treatment of advanced stage squamous cell NSCLC.

      Phase III, randomized, open-label, multi-center study of nab-paclitaxel with best supportive
      care (BSC) or BSC alone as maintenance treatment after response or stable disease (SD) with
      nab-paclitaxel plus carboplatin as induction in subjects with stage IIIB/IV squamous cell
      NSCLC.

      Subjects who discontinued treatment from the maintenance part for any reason other than
      withdrawal of consent, lost to follow-up, or death, were entered into a Follow-up period that
      had a visit 28 days after progression or discontinuation.

      Those who entered Follow-up without progression continued with follow-up scans according to
      standard of care (SOC) until documentation of progression of disease. Additionally, subjects
      were followed for OS by phone approximately every 90 days for a minimum of 18 months, for up
      to approximately 5 years after the last subject was randomized.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18 years of age at the time of signing the Informed Consent Form.

          2. Understand and voluntarily provide written consent to the Informed Consent Form prior
             to conducting any study related assessments/procedures.

          3. Able to adhere to the study visit schedule and other protocol requirements

             Disease Specific

          4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell Non Small
             Cell Lung Cancer at study entry.

          5. No other current active malignancy requiring anticancer therapy.

          6. Radiographically documented measurable disease at study entry (as defined by the
             Response Evaluation Criteria In Solid Tumors [RECIST] v1.1 criteria).

          7. No prior chemotherapy for the treatment of metastatic disease at study entry. Adjuvant
             chemotherapy is permitted providing cytotoxic chemotherapy was completed 12 months
             prior to starting the study and without disease recurrence.

          8. Absolute neutrophil count ≥ 1500 cells/mm^3.

          9. Platelets ≥ 100,000 cells/mm^3.

         10. Hemoglobin ≥ 9 g/dL.

         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 × upper limit of normal range except in cases of Gilbert's
             disease and liver metastases.

         13. Creatinine ≤ 1.5 mg/dL.

         14. Expected survival of > 12 weeks for the Induction part of the study.

         15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

         16. For Maintenance part of the study, subjects must have received at least one dose of
             nab-paclitaxel in each of the 4 cycles during Induction

             Pregnancy

         17. Females of childbearing potential [defined as a sexually mature woman 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 (i.e., has had menses at any time during the
             preceding 24 consecutive months)] must:

               1. agree to take a pregnancy test prior to starting study medication and throughout
                  the study participation.

               2. commit to complete abstinence from heterosexual contact, or agree to use medical
                  doctor-approved contraception throughout the study without interruption, and
                  while receiving study medication or for a longer period if required by local
                  regulations.

         18. Male subjects must:

             c. agree to complete abstinence from heterosexual contact or use a condom during
             sexual contact with a female of child bearing potential while receiving study
             medication and within 6 months after last dose of study medication, even if he has
             undergone a successful vasectomy.

         19. Females must abstain from breastfeeding during study participation and 3 months after
             IP discontinuation.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment into the
        Induction and Maintenance parts of the study (except if specified at study entry only):

          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 first dose of study drug).

          2. Only evidence of disease is non-measurable at study entry.

          3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria
             for Adverse Events v4.0).

          4. Venous thromboembolism within 6 months prior to signing Informed Consent Form.

          5. Current congestive heart failure (New York Heart Association class II-IV).

          6. 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 (NYHA) Class III-IV heart failure,
             uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically
             significant electrocardiogram (ECG) abnormality, cerebrovascular accident, transient
             ischemic attack, or seizure disorder.

          7. Treatment with any investigational product within 28 days prior to signing Informed
             Consent Form.

          8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.

          9. Currently enrolled in any other clinical protocol or investigational trial that
             involved administration of experimental therapy and/or therapeutic devices.

         10. Any other clinically significant medical condition and/or organ dysfunction that will
             interfere with the administration of the therapy according to this protocol.

         11. Subject 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 (TNM stage of T1a or T1b) - all
             treatments that should have been completed 6 months prior to signing informed consent
             form (ICF).

         12. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation
             ≤ 2 weeks prior to starting investigational product (IP), 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.

         13. Pregnant and nursing females.