Cisplatin or Carboplatin and Etoposide With or Without Vandetanib in Treating Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer or High-Grade or Poorly Undifferentiated Neuroendocrine Cancer
This randomized phase II trial studies how well cisplatin or carboplatin and etoposide with or without vandetanib works in treating patients with previously untreated extensive stage small cell lung cancer or high-grade or poorly differentiated neuroendocrine cancer. Drugs used in chemotherapy, such as cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving cisplatin or carboplatin and etoposide is more effective with or without vandetanib in treating small cell lung cancer or neuroendocrine cancer.
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information; NOTE: HIPAA authorization may be included in the informed consent or obtained separately
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 14 days prior to being registered for protocol therapy
- 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; NOTE: subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
- Females must not be breastfeeding
- Histological or cytological proof of chemotherapy-naive, extensive, small cell lung cancer or neuroendocrine cancers that are either high grade or poorly differentiated
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) and obtained by imaging within 30 days prior to being registered for protocol therapy
- No prior epidermal growth factor receptor (EGFR) inhibitor or antiangiogenic agent allowed
- No prior hormonal therapy for lung cancer
- Platelets >= 100K/mm^3
- Absolute neutrophil count (ANC) >= 1.5K/mm^3
- Serum creatinine < 1.5 x upper limit of normal (ULN) or calculated creatinine clearance of >= 45 cc/min using the Cockcroft-Gault formula
- Bilirubin =< 1.5 x ULN
- Aspartate aminotransferase (AST) =< 2.5 x ULN or =< 5 x ULN if judged by the investigator to be related to liver metastases
- Alkaline phosphatase =< 2.5 x ULN or =< 5 x ULN if judged by the investigator to be related to liver metastases
- Potassium within normal range (supplementation is allowed)
- Calcium within normal range (supplementation is allowed)
- Magnesium within normal range (supplementation is allowed)
- No symptomatic brain metastasis; (note: patients with treated brain metastasis must be off steroids or on tapering or stable doses of steroids and have completed radiation at least 14 days prior to registration for protocol therapy)
- 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 clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >= 2 within 3 months prior to registration for protocol therapy
- No presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia
- No history of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events [CTCAE] grade 3) or asymptomatic sustained ventricular tachycardia; atrial fibrillation, controlled on medication is permitted
- No previous history of corrected QT (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 blocks (LBBB)
- No QTc with Bazett’s correction that is unmeasurable, or >= 480 msec on screening electrocardiogram (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; NOTE: co-administration of drugs that in some reports might be associated with Torsades de Pointes but at this time lack substantial evidence of Torsades de Pointes should be avoided within 2 weeks of randomization and during study; however, these drugs will be allowed, at the discretion of the investigator, if considered absolutely necessary; in such cases, the subject must be closely monitored including regular checks of QTc and electrolytes; for patients who start on the drugs in this group while on the study treatment, the ECG must be checked within 24 hours of commencing the concomitant medication and then at least once per week while the patient remains on the medication; the frequency of ECG monitoring could revert to the standard schedule if no QTc prolongation has been noted during 4 weeks of co-administration of a drug; the electrolytes should be maintained within the normal range using supplements if necessary
- Must have QTc < 460 msec for patients receiving drugs that have a risk of inducing Torsades de Pointes within 7 days prior to registration for protocol therapy
- 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 other active cancers
- 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 cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) function
- Prior radiation therapy must be completed at least 14 days prior to registration for protocol therapy
Locations & Contacts
Trial Objectives and Outline
I. To evaluate whether the addition of ZD6474 (vandetanib) to etoposide and cisplatin/carboplatin (EP) improves time to disease progression over EP alone.
I. Evaluate the safety and tolerability of this treatment combination.
II Response rate (complete response [CR] + partial response [PR]) in each arm.
III. Disease control rate (CR + PR+ stable disease [SD]) in each arm.
IV. Overall survival for each arm.
I. Assess vascular endothelial growth factor (VEGF) polymorphisms and correlate subject response.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cisplatin or carboplatin intravenously (IV) on day 1, etoposide IV on days 1-3, and placebo orally (PO) daily on days 1-21. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive cisplatin or carboplatin and etoposide as in Arm A and vandetanib PO daily on days 1-21. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Trial Phase & Type
Hoosier Oncology Group
Nasser H. Hanna
Secondary IDs NCI-2013-00309, 1011004344, IRUSZACT0083, 0712-21
Clinicaltrials.gov ID NCT00613626