Phase III of RRM1 & ERCC1 Directed Customized Chemotherapy for the Treatment of Patients With NSCLC
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Docetaxel; Vinorelbine; Carboplatin; Gemcitabine
Intervention description: GD Group: 40 mg/m^2 on days 1 and 8, every 21 days
DCb Group: 75 mg/m^2 on day 1
DV Group: 50 mg/m^2 on days 1 and 15, every 28 days; DV Group: 35 mg/m^2 on days 1 and 15; GCb Group: Area under the curve (AUC) 5 on day 1, every 21 days
DCb Group: AUC 6 on day 1, every 21 days
Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.; GCb Group: 1,250 mg/m^2 on days 1 and 8
GD Group: 1,250 mg/m^2 on days 1 and 8
Control Arm: Patients received up to 6 cycles, and no maintenance therapy was allowed.
Intervention MeSH terms: Carboplatin; Gemcitabine; Docetaxel; Vinorelbine; Antineoplastic Agents
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 275.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RRM1; ERCC1; Customized Chemotherapy

Summary:

      This is a clinical research study to evaluate if chemotherapy in the experimental arm (E)
      results in a better outcome compared to patients in the standard of care arm (C).

      2:1 randomization to experimental arm (E) or standard arm (C). In arm E, treatment of
      dual-agent chemotherapy will be selected based on RRM1 and ERCC1 expression at the protein
      level. In arm C, treatment of dual-agent chemotherapy will be gemcitabine/carboplatin, i.e.,
      standard of care.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed Non-Small Cell Lung Cancer (NSCLC) of adenocarcinoma,
             squamous cell carcinoma, large cell carcinoma, or NSCLC not otherwise specified.
             Patients with suspected NSCLC may enroll prior to the diagnostic biopsy in order to
             obtain both the diagnostic and molecular analysis-required specimen during the same
             procedure. Must have blood work within 30 days prior to biopsy to eliminate any
             unnecessary biopsies on patients that do not qualify (screen failures) due to
             laboratory values that do not meet the inclusion/exclusion criteria. If a patient has
             blood work obtained at an outside facility, this can be utilized for the preliminary
             assessment prior to biopsy, but final inclusion/exclusion values must be obtained
             within 14 days of start of treatment.

          -  Willing to undergo biopsy to enable customization of chemotherapy

          -  Stage IV or IIIB (malignant pleural effusion) NSCLC

          -  Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors
             (RECIST)

          -  Performance status 0 or 1 by Eastern Cooperative Oncology Group (ECOG) criteria

          -  Adequate bone marrow function as evidenced by the following (assessed within 14 days
             of starting treatment): Absolute neutrophil count >= 1,500/mm³, Platelet count >=
             100,000/mm³, Hemoglobin >= 8.0 gm/dL

          -  Prothrombin time (PT) and activated prothrombin time with thromboplastin and kaolin
             (APTT) within normal laboratory ranges

          -  Serum creatinine <= 1.5 x upper limit of normal (ULN) assessed within 14 days of
             starting treatment

          -  Adequate liver function as evidenced by the following (assessed within 14 days of
             starting treatment): Total bilirubin must be within normal limits; aspartic
             transaminase (AST) and alanine transaminase (ALT) <= 2.5 x ULN with a normal alkaline
             phosphatases; alkaline phosphatases <= 4 x upper limit of normal with normal AST and
             ALT; patients with elevations of alk phos and AST and/or ALT will be excluded

          -  Serum calcium <= 1.1 x ULN

          -  Signed informed consent document

          -  Women of childbearing potential must have a negative pregnancy test. Men with partners
             in the childbearing age group and women of childbearing potential must use effective
             contraception while on treatment and for 6 months thereafter.

          -  Previous surgery for NSCLC (more that 30 days before study entry)

          -  Previous radiotherapy (RT) is allowed if: the time between completion of RT and
             initiation of chemotherapy is at least 7 days; the patient has fully recovered from
             all toxic effects; at least one target lesion or evaluable disease is outside the
             radiation field

          -  Previous chemotherapy allowed if the last dose was administered equal to or greater
             than 12 months ago. This chemotherapy must have been given in an adjuvant or
             neoadjuvant mode prior to or after a complete surgical resection (R0 resection) for a
             NSCLC.

          -  Patients with stable brain metastases will be allowed to enroll. Stable brain
             metastases being defined as no progression of brain metastases 28 days after
             conclusion of definitive treatment as documented by a computed tomography (CT) scan or
             magnetic resonance imaging (MRI) of the brain. Patients with incidentally discovered
             asymptomatic brain metastases may be enrolled and treated with chemotherapy without
             prior brain irradiation if deemed feasible by the treating physician.

        Exclusion Criteria:

          -  Pregnant or lactating

          -  Prior systemic chemotherapy or immunotherapy for advanced NSCLC.

          -  Prior malignancies, except: cured non-melanoma skin cancer curatively treated in situ
             carcinoma of the cervix any other curatively treated malignancy with no evidence of
             disease recurrence for at least 3 years

          -  Presence of uncontrolled brain or leptomeningeal metastases

          -  Peripheral neuropathy or hearing loss of neural origin equal to or greater than grade
             2 by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 except if due to
             trauma

          -  Other serious illness or medical condition, including but not limited to: congestive
             heart failure, myocardial infarction within 6 months, significant neurologic or
             psychiatric disorders that would impact study participation as judged by the treating
             physician or study chair, infection requiring intravenous (IV) antibiotics,
             tuberculosis with ongoing therapy at study entry, superior vena cava syndrome (except
             if controlled with radiation), active peptic ulcer disease, uncontrolled diabetes
             mellitus as judged by the treating oncologist, any contraindication to high dose
             corticosteroid therapy (such as herpes simplex, herpes zoster, hepatitis, or other
             disease)

          -  Hypercalcemia requiring therapeutic intervention

          -  Clinically significant ascites and/or pericardial effusion

          -  Patients with a history of severe hypersensitivity reaction to docetaxel or other
             drugs formulated with polysorbate 80

          -  Concurrent treatment with other investigational drugs