Status:
COMPLETED
A Randomized Phase II Study of Cisplatin and Etoposide in Combination With Either Hedgehog Inhibitor GDC-0449 or IGF-1R MOAB IMC-A12 for Patients With Extensive Stage
Lead Sponsor:
National Cancer Institute (NCI)
Conditions:
Extensive Stage Small Cell Lung Carcinoma
Recurrent Small Cell Lung Carcinoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This randomized phase II trial studies cisplatin and etoposide to see how well they work when given with or without Hedgehog inhibitor GDC-0449 (vismodegib) or IGF-1R MOAB IMC-A12 (cixutumumab) in tre...
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the progression-free survival (PFS) of patients with extensive stage small cell lung cancer (SCLC-ED) treated with cisplatin and etoposide (CE), CE with hedgehog (H...
Eligibility Criteria
Inclusion
- Histologically or cytologically confirmed small cell lung cancer (SCLC)
- Extensive stage SCLC
- Extensive stage disease: the extensive disease classification for this protocol includes all patients with disease sites not defined as limited stage; limited stage disease category includes patients with disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and/or ipsilateral supraclavicular nodes; extensive disease patients are defined as those patients with extrathoracic metastatic disease, malignant pleural effusion, bilateral or contralateral supraclavicular adenopathy
- Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST); baseline measurements and evaluations of all sites of disease must be obtained =\< 4 weeks prior to randomization
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Absolute neutrophil count (ANC) \>= 1,500/mm\^3
- Platelets \>= 100,000/mm\^3
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase) =\< 3 x institutional ULN (=\< 5 x ULN if liver function test \[LFT\] elevations are due to liver metastases)
- Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels \> 1.5 x institutional ULN
- Leukocytes \>= 3,000/mm\^3
- Hemoglobin \>= 9 g/dL
- Fasting serum glucose \< 120 mg/dL or below institutional ULN =\< 7 days prior to protocol randomization
- Patients with 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
- NOTE: the use of prophylactic cranial irradiation (recommended dose 25 Gy) in those who completed protocol chemotherapy and have a response (in the absence of progressive disease \[PD\]) is allowed; for patients on Arms B and C, GDC-0449 and IMC-A12 will be held while patient is receiving prophylactic cranial irradiation (PCI); these agents can be reinstituted after PCI is completed
- Women of child-bearing potential (WCBP) 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
- 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
- NOTE: the WCBP randomized to Arm B must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following two additional time periods related to this study: 1) while participating in the study; and 2) for at least 12 months after discontinuation from the study
- Before starting the study drugs, all WCBP must have a negative pregnancy test (sensitivity of at least 50 mIU/mL); the pregnancy test must be performed within 10-14 days prior to randomization
- NOTE: the WCBP randomized to Arm B must have a second pregnancy test performed within the 24 hours prior to the start of the GDC-0449; the subject may not receive GDC-0449 until the investigator has verified that the results of these pregnancy tests are negative
- The WCBP randomized to Arm B will be warned that sharing the study drug is prohibited and will be counseled about pregnancy precautions and potential risks or fetal exposure; she must also agree to abstain from donating blood during study participation and at least 12 months after discontinuation from the study drug
- NOTE: male subjects randomized to Arm B must agree to use a latex condom during sexual contact with WCBP while participating in the study and for at least 12 months following discontinuation from the study even if he has undergone a successful vasectomy
- Male subjects randomized to Arm B will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure; male subjects must agree to abstain from donating blood, semen, or sperm during study participation and for at least 3 months after discontinuation from the study drug
Exclusion
- Pregnant or breastfeeding; all WCBP must have a blood test within 10-14 days prior to randomization to rule out pregnancy
- 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
- Receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biological composition to GDC-0449 and IMC-A12 or other agents used in the study
- 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
- 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 with major surgery, hormonal therapy (other than replacement), within 4 weeks prior to entering the study or those who have not recovered from adverse events
- Prior treatment with other agents targeting the IGFR or the Hedgehog signaling pathway
Key Trial Info
Start Date :
July 16 2009
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 15 2016
Estimated Enrollment :
168 Patients enrolled
Trial Details
Trial ID
NCT00887159
Start Date
July 16 2009
End Date
November 15 2016
Last Update
January 5 2021
Active Locations (301)
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1
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
2
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States, 94304
3
The Medical Center of Aurora
Aurora, Colorado, United States, 80012
4
Boulder Community Hospital
Boulder, Colorado, United States, 80301