|Phase II||Treatment||Closed||18 and over||NCI||NCI-2011-01917|
ECOG-E1508, CDR0000640898, E1508, U10CA021115, NCT00887159
This randomized phase II trial is studying cisplatin and etoposide phosphate to see how well they work when given with or without vismodegib or cixutumumab in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vismodegib may slow the growth of tumor cells. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving cisplatin and etoposide phosphate are more effective when given together with vismodegib or cixutumumab in treating small cell lung cancer.
Further Study Information
I. To evaluate the progression-free survival of patients with extensive stage small cell lung cancer (SCLC-ED) treated with cisplatin and etoposide (etoposide phosphate) (CE), CE with hedgehog (HH) inhibitor GDC-0449 (vismodegib), and CE with Insulin-like Growth Factor-I Receptor (IGF-1R) Monoclonal Antibody (IMC-A12) (cixutumumab).
I. To evaluate response rate, overall survival, and toxicity of patients with SCLC-ED treated with CE, CE with GDC-0449, and CE with IMC-A12.
II. To explore putative correlates of clinical benefit from combination therapy in tumor and circulating tumor cells in patients treated on this protocol.
OUTLINE: This is a multicenter study. Patients are stratified according to gender. Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive cisplatin intravenously (IV) over 1-2 hours on day 1 and etoposide phosphate IV over 1-2 hours on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive cisplatin and etoposide phosphate as in arm I and vismodegib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive vismodegib alone QD in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive cisplatin and etoposide phosphate as in arm I and cixutumumab IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cixutumumab alone once weekly in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
- Histologically or cytologically confirmed small cell lung cancer (SCLC)
- Extensive stage disease, as defined by any of the following criteria:
- Extrathoracic metastatic disease
- Malignant pleural effusion
- Bilateral or contralateral supraclavicular adenopathy
- Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Total bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 times institutional upper limit of normal (IULN) (=< 5 times ULN if liver function test [LFT] elevations are due to liver metastases)
- Creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73m^2 for patients with creatinine levels > 1.5 x IULN
- Leukocyte count >= 3,000/mm^3
- Hemoglobin >= 9 g/dL
- Fasting serum glucose < 120 mg/dL or below IULN =< 7 days prior to protocol randomization
- Central nervous system (CNS) metastases will be eligible if they have completed a course of CNS radiotherapy and have stable neurologic function for a minimum of 28 days prior to study randomization; radiotherapy must have been completed a minimum of 28 days prior to randomization, and patients must have recovered from any adverse events related to the radiotherapy (except alopecia and grade 1 neuropathy) and have stable neurologic function for a minimum of 28 days prior to study randomization
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- Women of childbearing potential (WCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse; the two methods of reliable contraception must include one highly effective method (i.e., intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, cervical cap); WCBP must be referred to a qualified provider of contraceptive methods if needed
- Male subjects randomized to Arm B must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study and for at least 12 months following discontinuation from the study even if he has undergone a successful vasectomy
- Women must not be pregnant or breastfeeding; all females of childbearing potential must have a blood test within 10-14 days prior to randomization to rule out pregnancy
- Fertile patients must use effective double-method contraception for ≥ 28 days before, during, and for ≥ 12 months after completion of study treatment
- Patients cannot have had prior chemotherapy or biologic therapy for SCLC; patients with prior radiation may be eligible or after palliative radiotherapy for other sites of disease; patients receiving prior radiation cannot start therapy within 14 days after completion of radiation, and must have recovered from adverse events attributed to radiation; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
- Patients may not be receiving any other investigational agents
- Patients must NOT have history of allergic reactions attributed to compounds of similar chemical or biological composition to Hedgehog antagonist GDC-0449, cixutumumab, or other agents used in the study
- Patients must NOT have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
- Patient must not have poorly controlled diabetes mellitus; patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below institutional upper limit of normal) and that they are on a stable dietary or therapeutic regimen for this condition
- Patients who have had major surgery, hormonal therapy (other than replacement), within 4 weeks prior to entering the study or those who have not recovered from adverse events are not eligible
- The patient must not have a history of treatment with other agents targeting the IGFR or the Hedgehog signaling pathway
- No prior irradiation to the only site of measurable or evaluable disease unless that site had subsequent evidence of progression
- Prior palliative radiotherapy to other sites of disease allowed
- More than 14 days since prior radiotherapy (28 days for radiotherapy to the CNS) and recovered
Trial Lead Organizations/Sponsors
National Cancer Institute
|Chandra Belani||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00887159
ClinicalTrials.gov processed this data on January 06, 2014
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