Cisplatin + Etoposide +/- Concurrent ZD6474 in Previously Untreated Extensive Stage Small Cell Lung Cancer
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Cisplatin; Etoposide; Placebo; ZD6474
Intervention description: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles; Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles; Matched placebo oral daily; ZD6474 100mg oral daily to be continued for the duration of the study.
Intervention MeSH terms: Etoposide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Extensive Stage; Untreated

Summary:

      At this point in the treatment of extensive stage SCLC, we have reached a plateau in survival
      with conventional chemotherapy and newer regimens are greatly needed. It has been noted that
      patients with increased VEGF levels have a poorer prognosis. Anti-angiogenic agents hold
      significant promise in the treatment of patients with extensive stage SCLC. ZD6474, a new
      inhibitor of the VEGFR-2, has shown favorable action in NSCLC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological proof of chemotherapy-naïve, extensive, small cell lung
             cancer.

          -  Measurable disease according to RECIST and obtained by imaging within 28 days prior to
             being registered for protocol therapy.

          -  Written informed consent and HIPAA authorization for release of personal health
             information.

          -  Age 18 years or older at the time of consent.

          -  Potassium ≥4.0 mmol/L and <5.5mmol/L (supplementation is allowed).

          -  Calcium within normal range (supplementation is allowed).

          -  Magnesium within normal range (supplementation is allowed).

        Exclusion Criteria:

          -  No prior EGFR inhibitor or antiangiogenic agent allowed.

          -  No prior hormonal therapy.

          -  No symptomatic brain metastasis.

          -  No clinically significant infections as judged by the treating investigator.

          -  No evidence of severe or uncontrolled other systemic disease or any concurrent
             condition which in the Investigator's opinion makes it undesirable for the subject to
             participate in the trial or which would jeopardize compliance with the protocol.

          -  No previous history of QTc prolongation as a result of medication that required
             discontinuation of that medication.

          -  No congenital long QT syndrome or known 1st degree relative with unexplained sudden
             death under 40 years of age.

          -  No presence of left bundle branch block (LBBB.)

          -  No QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG
             obtained within 7 days prior to registration for protocol therapy. If a subject has
             QTc ≥480 msec on screening ECG, the screen ECG may be repeated twice (at least 24
             hours apart). The average QTc from the three screening ECGs must be <480 msec in order
             for the subject to be eligible for the study.

          -  No concomitant (within 14 days prior to registration for and during protocol therapy)
             medication associated with Torsades de Pointes or cause QTc prolongation, is allowed.
             Medications that prolong QT, but are not strictly associated with Torsades, are
             allowed if medically necessary and will require increased ECG and electrolyte
             monitoring.

          -  No uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or
             diastolic blood pressure greater than 100 mm Hg).

          -  No currently active diarrhea that may affect the ability to absorb ZD6474.

          -  No prior malignancy is allowed except for adequately treated basal cell or squamous
             cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or
             other cancer for which the subject has been disease-free for at least 5 years.

          -  Major surgery must be completed greater than 28 days prior to registration for
             protocol therapy and healed surgical incision is required.

          -  No concomitant (within 14 days prior to registration for and during protocol therapy)
             medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine,
             phenobarbital and St. John's Wort) of CYP3A4 function.

          -  Females of childbearing potential and males must be willing to use an effective method
             of contraception (hormonal or barrier method of birth control; abstinence) from the
             time consent is signed until 8 weeks after treatment discontinuation.

          -  Females of childbearing potential must have a negative pregnancy test within 7 days
             prior to being registered for protocol therapy.

          -  Females must not be breastfeeding.