First-line Treatment Of Subjects With Extensive Disease Small Cell Lung Cancer With Weekly Hycamtin And Paraplatin
Condition: Lung Cancer, Small Cell
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: topotecan; carboplatin
Intervention description: Hycamtin and Carboplatin as first-line treatment of chemonaive subjects with EX-SCLC.; Hycamtin and Carboplatin as first-line treatment of chemonaive subjects with EX-SCLC.
Intervention MeSH terms: Carboplatin; Topotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: chemonaive; small cell lung cancer; untreated; Lung cancer; HYCAMTIN; first-line; extensive disease

Summary:

      This study was designed to find the safest and most effective dose of a combination of two
      chemotherapy drugs, Hycamtin® (topotecan) and Paraplatin® (carboplatin), in people with
      extensive disease small cell lung cancer.
    

Eligibility criteria:

        Inclusion criteria:

          -  Adequate contraception methods include: systemic contraceptives or IUD for 3 months
             prior to start of the study medication or diaphragm plus spermicide; for males, condom
             plus spermicide; or total abstinence from sexual intercourse during the course of the
             study

          -  Women of childbearing potential and sexually active males must practice or use an
             accepted and effective form of contraception

          -  Subjects who present with CNS metastases are eligible, provided the attending
             physician ascertains that the metastases are controlled before the start of
             chemotherapy, and the subject is asymptomatic on neurologic exam and is not receiving
             corticosteroid therapy to control symptoms. Continued use of other anti-seizure
             medication is permitted

          -  Free of active infection

          -  At screening, a probable life expectancy of at least 3 months

          -  No prior chemotherapy for SCLC or any chemotherapy within 5 years of the diagnosis of
             SCLC. Prior radiation to any symptomatic site is permitted provided that the indicator
             lesion site(s) are not irradiated, and radiation is completed before chemotherapy is
             started

          -  Performance status ECOG 0-1

          -  Adequate hematologic, renal and hepatic function •Hematologic: ANC 1500/mm3 [1.5 x
             109/L], platelet count 100,000/L (100 x 109/L), hemoglobin 9.0 g/dL

          -  Renal: Serum Creatinine ≤1.5mg/dL (133mol/L) and CrCl 60 ml/min (Cockroft-Gault)
             [Cockroft, 1976]

        CrCl may be calculated using the Cockcroft-Gault formula:

        CrCl (ml/min) = Q x (140-age [yr]) x body wt [kg] 72 x serum creatinine [mg/dl] Q = 0.85
        for females Q = 1.0 for males CrCl (ml/min) = K x (140-age [yr]) x body wt [kg] Serum
        creatinine [mol/L] K = 1.0 for females K = 1.23 for males

          -  Hepatic: Serum bilirubin (1.5 mg/dL), SGOT (AST), SGPT (ALT) and Alkaline Phosphatase
             2 times the upper limit of normal (ULN) if liver metastases are absent by abdominal CT
             or MRI, or 5 times ULN if liver metastases are present

          -  At least 18 years old

          -  Written informed consent (subject's written understanding of and agreement to
             participate in this study.

          -  Subject with histologically-confirmed extensive small cell lung cancer or
             unequivocally positive positive cytological evidence (sputum, at least two, or
             aspirate biopsy)

          -  Presence of measurable disease according to World Health Organization (WHO)* criteria,
             as determined by diagnostic tests, including CT scan of the chest and abdomen, or MRI
             scan of the brain, or CXR, or PET CT, MRI, and/or CXR are the preferred diagnostic
             methods to evaluate disease during the course of this study. Use of positron-emission
             tomography (PET) is not required, but is permitted if it is the standard diagnostic
             tool employed by the institution. Measurable disease - Presence of at least one
             bidimensionally measurable, non-CNS lesion (indicator lesion). If the measurable
             disease is restricted to a solitary lesion, its neoplastic nature should be confirmed
             by cytology/histology • Measurable disease, either on CT or MRI scan, requires one
             diameter 1 cm and one diameter 2 cm. • Measurable disease on CXR requires both
             diameters 2 cm. • Palpable tumor masses that could not be evaluated radiologically
             require two diameters 2 cm

          -  At least 3 weeks since last major surgery (a lesser period is acceptable if decided to
             be in the best interest of the subject).

          -  Subjects with central nervous system metastases are eligible as long as the attending
             doctor determines that the metastases are under control before the start of
             chemotherapy, and the subject has no symptoms of spreading of disease to the brain,
             and is not receiving drugs called steroids to control the symptoms.

          -  Laboratory criteria: Subjects must have adequate bone marrow reserve and adequate
             kidney and liver function.

        Exclusion criteria:

          -  Concurrent or planned chemotherapy, immunotherapy, radiotherapy, or investigational
             therapy for the treatment of SCLC. (Concurrent radiation for palliation of bone
             metastases and CNS lesions must be discussed with and approved by the GlaxoSmithKline
             Medical Monitor)

          -  Concurrent severe medical problems other than the diagnosis of SCLC, which would
             significantly limit full compliance with the study or expose the patient to extreme
             risk

          -  Concomitant malignancies or previous malignancies other than SCLC within the last 5
             years, with the exception of adequately treated basal or squamous cell carcinoma of
             the skin, carcinoma in situ of the cervix, or localized low grade prostate cancer
             (contact GlaxoSmithKline Medical Monitor to discuss enrolment of subjects with low
             grade prostate cancer)

          -  Present clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed
             by CT or MRI brain scan, or corticosteroid treatment to control symptoms of brain
             metastases

          -  Uncontrolled infection

          -  Ongoing tumor or previous tumor other than lung cancer within the last 5 years.

          -  Symptoms of spreading of the disease to the brain that requires treatment with drugs
             called steroids

          -  Severe medical problems other than the diagnosis of SCLC that would limit the ability
             of the subject to follow study plan or that would expose the subject to extreme risk.

          -  Ongoing or planned chemotherapy, immunotherapy, radiation treatment, or other
             experimental drug therapy for the treatment of SCLC.

          -  Use of investigational drug within 30 days or 5 half-lives (whichever is longer)
             preceding the first dose of study medication

          -  Women who are pregnant or lactating.

          -  Women who can become pregnant who refuse to practice an adequate form of birth
             control.

          -  Subjects with history of allergic reaction to chemicals related to HYCAMTIN and
             PARAPLATIN.

          -  Subjects with pre-existing heart disease, such as congestive heart failure, irregular
             heartbeats that require treatment, and heart attack within the last 3-months.