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 treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Etoposide may slow the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vismodegib may slow the growth of tumor cells. Monoclonal antibodies, such as cixutumumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving cisplatin and etoposide are more effective when given together with vismodegib or cixutumumab in treating small cell lung cancer.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

168

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Jul 2009

Longer than P75 for phase_2

Geographic Reach

1 country

301 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7.3 years study duration

First Submitted

Initial submission to the registry

April 22, 2009

Completed

1 day until next milestone

First Posted

Study publicly available on registry

April 23, 2009

Completed

3 months until next milestone

Study Start

First participant enrolled

July 16, 2009

Completed

6 years until next milestone

Results Posted

Study results publicly available

July 29, 2015

Completed

1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 15, 2016

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 15, 2016

Completed

Last Updated

January 5, 2021

Status Verified

December 1, 2020

Enrollment Period

7.3 years

First QC Date

April 22, 2009

Results QC Date

July 1, 2015

Last Update Submit

December 10, 2020

Conditions

Extensive Stage Small Cell Lung Carcinoma Recurrent Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (1)

Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the time from randomization to death or disease progression, whichever occurred first. Patients who were alive at the time of analysis are censored at the date at which they are last known to be alive and progression-free.
Assessed every 6 weeks while on treatment or observation; follow-up after discontinuation of treatment or observation: every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry

Secondary Outcomes (3)

Response Rate
Assessed every 6 weeks while on treatment or observation; follow-up after discontinuation of treatment or observation: every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry
Overall Survival (OS)
Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry
PFS
Assessed every 6 weeks while on treatment or observation; follow-up after discontinuation of treatment or observation: every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry

Study Arms (3)

Arm A (CE)

ACTIVE COMPARATOR

Patients receive cisplatin IV over 1-2 hours on day 1 and etoposide 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.

Drug: CisplatinDrug: EtoposideOther: Laboratory Biomarker Analysis

Arm B (CE + GDC-0449)

EXPERIMENTAL

Patients receive cisplatin and etoposide as in Arm A and vismodegib PO 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.

Drug: CisplatinDrug: EtoposideOther: Laboratory Biomarker AnalysisDrug: Vismodegib

Arm C (CE + IMC-A12)

EXPERIMENTAL

Patients receive cisplatin and etoposide as in Arm A 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.

Drug: CisplatinBiological: CixutumumabDrug: EtoposideOther: Laboratory Biomarker Analysis

Interventions

CisplatinDRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (CE)Arm B (CE + GDC-0449)Arm C (CE + IMC-A12)

CixutumumabBIOLOGICAL

Given IV

Also known as: Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12, IMC-A12

Arm C (CE + IMC-A12)

EtoposideDRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Arm A (CE)Arm B (CE + GDC-0449)Arm C (CE + IMC-A12)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm A (CE)Arm B (CE + GDC-0449)Arm C (CE + IMC-A12)

VismodegibDRUG

Given PO

Also known as: Erivedge, GDC-0449, Hedgehog Antagonist GDC-0449

Arm B (CE + GDC-0449)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
+8 more criteria

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (301)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

The Medical Center of Aurora

Aurora, Colorado, 80012, United States

Location

Boulder Community Hospital

Boulder, Colorado, 80301, United States

Location

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, 80907, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, 80218, United States

Location

SCL Health Saint Joseph Hospital

Denver, Colorado, 80218, United States

Location

Rose Medical Center

Denver, Colorado, 80220, United States

Location

Colorado Cancer Research Program NCORP

Denver, Colorado, 80222, United States

Location

Swedish Medical Center

Englewood, Colorado, 80113, United States

Location

Saint Mary's Hospital and Regional Medical Center

Grand Junction, Colorado, 81501, United States

Location

North Colorado Medical Center

Greeley, Colorado, 80631, United States

Location

Saint Anthony Hospital

Lakewood, Colorado, 80228, United States

Location

Sky Ridge Medical Center

Lone Tree, Colorado, 80124, United States

Location

Longmont United Hospital

Longmont, Colorado, 80501, United States

Location

McKee Medical Center

Loveland, Colorado, 80539, United States

Location

Saint Mary Corwin Medical Center

Pueblo, Colorado, 81004, United States

Location

North Suburban Medical Center

Thornton, Colorado, 80229, United States

Location

SCL Health Lutheran Medical Center

Wheat Ridge, Colorado, 80033, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, 06790, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Atlanta VA Medical Center

Decatur, Georgia, 30033, United States

Location

Medical Center of Central Georgia

Macon, Georgia, 31201, United States

Location

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, 31405, United States

Location

Illinois CancerCare-Bloomington

Bloomington, Illinois, 61704, United States

Location

Graham Hospital Association

Canton, Illinois, 61520, United States

Location

Illinois CancerCare-Canton

Canton, Illinois, 61520, United States

Location

Illinois CancerCare-Carthage

Carthage, Illinois, 62321, United States

Location

Memorial Hospital

Carthage, Illinois, 62321, United States

Location

Hematology and Oncology Associates

Chicago, Illinois, 60611, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, 60612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Presence Saint Joseph Hospital-Chicago

Chicago, Illinois, 60657, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Heartland Cancer Research NCORP

Decatur, Illinois, 62526, United States

Location

Elmhurst Memorial Hospital

Elmhurst, Illinois, 60126, United States

Location

Eureka Hospital

Eureka, Illinois, 61530, United States

Location

Illinois CancerCare-Eureka

Eureka, Illinois, 61530, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Galesburg Cottage Hospital

Galesburg, Illinois, 61401, United States

Location

Illinois CancerCare-Galesburg

Galesburg, Illinois, 61401, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Illinois CancerCare-Havana

Havana, Illinois, 62644, United States

Location

Mason District Hospital

Havana, Illinois, 62644, United States

Location

Hematology Oncology Associates of Illinois-Highland Park

Highland Park, Illinois, 60035, United States

Location

Hinsdale Hematology Oncology Associates Incorporated

Hinsdale, Illinois, 60521, United States

Location

Joliet Oncology-Hematology Associates Limited

Joliet, Illinois, 60435, United States

Location

Presence Saint Mary's Hospital

Kankakee, Illinois, 60901, United States

Location

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, 61443, United States

Location

NorthShore Hematology Oncology-Libertyville

Libertyville, Illinois, 60048, United States

Location

Illinois CancerCare-Macomb

Macomb, Illinois, 61455, United States

Location

Mcdonough District Hospital

Macomb, Illinois, 61455, United States

Location

Garneau, Stewart C MD (UIA Investigator)