Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer or Metastatic Large Cell Neuroendocrine Non-Small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01642251
First received: July 13, 2012
Last updated: October 17, 2014
Last verified: June 2014
  Purpose

This randomized phase I/II trial studies the side effects and best dose of veliparib when given together with or without cisplatin and etoposide and to see how well they work in treating patients with extensive stage small cell lung cancer or metastatic large cell neuroendocrine non-small cell lung cancer . Drugs used in chemotherapy, such as cisplatin and etoposide, 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. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cisplatin and etoposide with or without veliparib may work better in treating patients with extensive stage small cell lung cancer or metastatic large cell neuroendocrine non-small cell lung cancer.


Condition Intervention Phase
Extensive Stage Small Cell Lung Cancer
Large Cell Lung Cancer
Metastatic Carcinoma of Unknown Primary
Neuroendocrine Carcinoma
Newly Diagnosed Carcinoma of Unknown Primary
Stage IV Non-small Cell Lung Cancer
Drug: veliparib
Other: placebo
Drug: etoposide
Drug: cisplatin
Other: laboratory biomarker analysis
Other: questionnaire administration
Other: quality-of-life assessment
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase I and Randomized Phase II Double Blind Clinical Trial of Cisplatin and Etoposide in Combination With Veliparib (ABT-888) or Placebo as Frontline Therapy for Extensive Stage Small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum-tolerated dose of veliparib based on the incidence of dose-limiting toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • PFS (Phase II) [ Time Frame: Time from randomization to documented disease progression or death from any cause, whichever occurs first, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated by the Kaplan-Meier and Cox proportional hazards models. Will be analyzed using Wilcoxon rank sum test, and multivariable linear regression models may be used to adjust for multiple associations with outcome.


Secondary Outcome Measures:
  • OS (Phase II) [ Time Frame: Time from randomization to death from any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated by the Kaplan-Meier and Cox proportional hazards models. Will be analyzed using Wilcoxon rank sum test, and multivariable linear regression models may be used to adjust for multiple associations with outcome.

  • Best objective response evaluated via RECIST 1.1 (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Data will be compared using Fisher's exact tests with a one-sided type I error rate of 10%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these outcomes.

  • Toxicity will be determined using the CTCAE version 4.0 criteria (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Chemotherapy-induced peripheral neuropathy (CIPN) will be assessed based on standard toxicity reporting as well as validated quality-of-life tools. Data will be compared using Fisher's exact tests with a one-sided type I error rate of 10%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these outcomes.


Other Outcome Measures:
  • Deoxyribonucleic acid-protein kinase expression by immunohistochemistry [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Protein expression will be quantified using intensity (0, 1+, 2+ or 3+) and H-score (product of intensity and percent positive staining).

  • Rate and of chemotherapy-induced peripheral neuropathy (CIPN) for each study arm [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be performed using Fisher's exact tests for categorical data and t-tests or Wilcoxon rank sum tests, depending on normality assumptions. Severity and mean duration of CIPN as reported by the patients using the self-administered questionnaire will also be analyzed.


Estimated Enrollment: 168
Study Start Date: September 2012
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (veliparib, etoposide, and cisplatin)
Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Active Comparator: Arm B (placebo, cisplatin, and etoposide)
Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Other: placebo
Given PO
Other Name: PLCB
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose (RP2D) of veliparib to use in combination with cisplatin and etoposide (CE). (Phase I) II. To determine whether the addition of ABT-888 (veliparib) to cisplatin etoposide (CE) results in improved progression free survival (PFS) over CE with placebo in the frontline therapy of newly diagnosed extensive stage small cell lung cancer. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the overall survival (OS) associated with the combination of CE plus ABT-888. (Phase II) II. To assess the overall response rate (ORR) as well as complete response rate (CRR) associated with the combination of CE plus ABT-888. (Phase II) III. To determine the toxicity profile of the combination of ABT-888 and CE chemotherapy in this patient population. (Phase II) IV. To conduct exploratory correlative analysis of the impact of select biomarkers. (Phase II) V. To compare the overall toxicity profile and specifically the incidence and severity of chemotherapy-induced peripheral neuropathy with the addition of ABT-888 to CE. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II study.

Phase I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, etoposide intravenously (IV) over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Phase II: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4 courses 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:

  • Women must not be pregnant or breastfeeding; breastfeeding must be discontinued or the subject is not eligible for the study
  • All females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
  • Patients must have histologically or cytologically confirmed:

    • Extensive stage small cell lung cancer (SCLC) or
    • Stage IV (M1a or M1b according to American Joint Committee on Cancer [AJCC] Staging Manual, 7th edition) large cell neuroendocrine non-small cell lung cancer (NSCLC) or
    • Small cell carcinoma of unknown primary or extrapulmonary origin and must be a candidate for systemic therapy

      • NOTE: The extensive disease SCLC 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
  • Patients must have measurable or non-measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; baseline measurements and evaluations of all sites of disease must be obtained =< 4 weeks prior to registration (Phase I)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Leukocytes >= 3,000/mm^3
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase[SGPT]) =< 3 times institutional ULN (=< 5 times if liver function test [LFT] elevations due to known liver metastases)
  • Creatinine =< 1.5 X ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x ULN
  • Patients with central nervous system (CNS) metastases or a history of CNS metastases are ineligible
  • Patients cannot have had prior chemotherapy or biologic therapy for SCLC or large cell neuroendocrine NSCLC, or small cell carcinoma of unknown primary or extrapulmonary origin; patients receiving prior radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
  • Patients receiving prior radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
  • Patients must NOT have active seizure(s) or history of seizure(s)
  • Patients must NOT have history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib 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 be able to swallow pills
  • PHASE II: Women must not be pregnant or breastfeeding; breastfeeding must be discontinued or the subject is not eligible for the study
  • PHASE II: All females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) with the current month counted as month 1
  • PHASE II: Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
  • PHASE II: Patients must have extensive stage, histologically or cytologically confirmed small cell lung cancer; NOTE: 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
  • PHASE II: Patients must have measurable disease based on RECIST 1.1; baseline measurements and evaluations of all sites of disease must be obtained =< 4 weeks prior to registration
  • PHASE II: ECOG performance status 0 or 1
  • PHASE II: Absolute neutrophil count >= 1,500/mm^3
  • PHASE II: Platelets >= 100,000/mm^3
  • PHASE II: Leukocytes >= 3,000/mm^3
  • PHASE II: Hemoglobin >= 9 g/dL
  • PHASE II: Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)
  • PHASE II: AST (SGOT) and ALT (SGPT) =< 3 times institutional ULN (=< 5 times if LFT elevations due to known liver metastases)
  • PHASE II: Creatinine =< 1.5 X ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 x ULN
  • PHASE II: Patients with CNS metastases or a history of CNS metastases are ineligible
  • PHASE II: Patients cannot have had prior chemotherapy or biologic therapy for small cell lung cancer; patients receiving prior radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
  • PHASE II: Patient must be able to swallow pills
  • PHASE II: Patients may not be receiving any other investigational agents while on study
  • PHASE II: Patients must NOT have history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in the study
  • PHASE II: Patients must NOT have active seizure(s) or history of seizure(s)
  • PHASE II: 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
  • PHASE II: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with veliparib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  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: NCT01642251

  Show 334 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Taofeek Owonikoko ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01642251     History of Changes
Other Study ID Numbers: NCI-2012-01985, NCI-2012-01985, U10CA021115, ECOG-E2511, CDR0000736704, E2511, E2511, U10CA021115, U10CA180820
Study First Received: July 13, 2012
Last Updated: October 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Neuroendocrine
Carcinoma
Neoplasms, Unknown Primary
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Etoposide phosphate
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014