Cisplatin and Etoposide With or Without Vismodegib or Cixutumumab in Treating Patients With Extensive-Stage Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00887159
First received: April 22, 2009
Last updated: July 1, 2015
Last verified: May 2015
  Purpose

This randomized phase II trial studies cisplatin and etoposide (CE) 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, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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, 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 are more effective when given together with vismodegib or cixutumumab in treating small cell lung cancer.


Condition Intervention Phase
Extensive Stage Small Cell Lung Cancer
Recurrent Small Cell Lung Cancer
Biological: cixutumumab
Drug: vismodegib
Drug: cisplatin
Drug: etoposide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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 Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Response Rate [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and persistence of one or more non-target lesion(s).

  • Overall Survival (OS) [ Time Frame: Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization to death or date of last known alive.

  • PFS [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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. This analysis is to evaluate the association between PFS and circulating tumor cells (CTCs).


Enrollment: 168
Study Start Date: July 2009
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A (CE)
Patients receive cisplatin (75 mg/m2) intravenously (IV) over 1-2 hours on day 1 and etoposide (100 mg/m2) 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: cisplatin
Given IV
Other Names:
  • NSC 119875
  • DDP
  • CDDP
  • DACP
  • Cis-diaminedichloroplatinum
  • Cis-diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
  • VePesid
  • epipodophyllotoxin
Experimental: Arm B (CE+GDC-0449)
Patients receive cisplatin and etoposide as in Arm A and vismodegib (GDC-0449; 150 mg tablet) 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.
Drug: vismodegib
Given PO
Other Names:
  • Erivedge
  • GDC-0449
  • Systemic Hedgehog Pathway Antagonist
  • G-025897
  • G-025897.1
Drug: cisplatin
Given IV
Other Names:
  • NSC 119875
  • DDP
  • CDDP
  • DACP
  • Cis-diaminedichloroplatinum
  • Cis-diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
  • VePesid
  • epipodophyllotoxin
Experimental: Arm C (CE+IMC-A12)
Patients receive cisplatin and etoposide as in Arm A and cixutumumab (IMC-A12; 6 mg/kg) 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.
Biological: cixutumumab
Given IV
Other Names:
  • IGF-1R MoAB
  • IMC-A12
Drug: cisplatin
Given IV
Other Names:
  • NSC 119875
  • DDP
  • CDDP
  • DACP
  • Cis-diaminedichloroplatinum
  • Cis-diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • cis-platinum
  • platinum
  • Platinol
  • Platinol-AQ
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
  • VePesid
  • epipodophyllotoxin

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 (HH) inhibitor GDC-0449 (vismodegib), and CE with Insulin-like Growth Factor-I Receptor (IGF-1R) Monoclonal Antibody (IMC-A12) (cixutumumab).

SECONDARY OBJECTIVES:

I. To evaluate response rate, overall survival, and toxicity for each arm. II. To explore putative correlates of clinical benefit from combination therapy in tumor and circulating tumor cells in patients treated on this protocol.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A (CE): Patients receive cisplatin (75 mg/m2) intravenously (IV) over 1-2 hours on day 1 and etoposide (100 mg/m2) 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 B (CE + GDC-0449): Patients receive cisplatin and etoposide as in Arm A and vismodegib (GDC-0449; 150 mg tablet) 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 C (CE + IMC-A12): Patients receive cisplatin and etoposide as in Arm A and cixutumumab (IMC-A12; 6 mg/kg) 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed small cell lung cancer (SCLC)
  • Extensive stage SCLC
  • Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST)
  • 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
  • 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 Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887159

  Show 270 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Chandra Belani Penn State Hershey Cancer Institute
  More Information

Publications:
Belani, C.P., Dahlberg, S.E., Rudin, C.M., Fleisher, M., Chen, H.X., Takebe, N., Ramalingam, S.S., Schiller, J.H.: Three-arm randomized phase II study of cisplatin and etoposide (CE) versus CE with either vismodegib (V) or cixutumumab (Cx) for patients with extensive stage-small cell lung cancer(ES-SCLC) (ECOG 1508). J Clin Oncol 2013(31)(15S). Abstract 7508.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00887159     History of Changes
Other Study ID Numbers: NCI-2011-01917, NCI-2011-01917, E1508, U10CA021115, U10CA180820
Study First Received: April 22, 2009
Results First Received: July 1, 2015
Last Updated: July 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
extensive stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Cisplatin
Etoposide
Etoposide phosphate
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on July 29, 2015