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Cisplatin and Etoposide With or Without Veliparib in Treating Patients With Extensive Stage Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01642251
Recruitment Status : Completed
First Posted : July 17, 2012
Results First Posted : February 5, 2019
Last Update Posted : February 5, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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 large cell neuroendocrine non-small cell lung cancer that has spread to other parts of the body. 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 or disease Intervention/treatment Phase
Extensive Stage Small Cell Lung Carcinoma Large Cell Lung Carcinoma Neuroendocrine Carcinoma Small Cell Carcinoma Stage IV Non-Small Cell Lung Cancer AJCC v7 Drug: Cisplatin Drug: Etoposide Drug: Veliparib Drug: Placebo Phase 1 Phase 2

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)

OTHER PRE-SPECIFIED OBJECTIVES:

I. To conduct exploratory correlative analysis of the impact of the select biomarkers. (Phase II) II. 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 D: 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 E: 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 156 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Study Start Date : September 28, 2012
Actual Primary Completion Date : December 8, 2016
Actual Study Completion Date : July 2, 2018


Arm Intervention/treatment
Experimental: Arm A (veliparib)
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: Cisplatin
Given IV
Other Names:
  • Cisdiaminedichloroplatinum
  • Cis -diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • Platinol -AQ
  • Cis-platinum
  • P latinol
  • platinum
  • DDP
  • CDDP
  • DACP
  • NSC 119875

Drug: Etoposide
Given IV
Other Names:
  • Epipodophyllotoxin
  • EPEG
  • Vepesid
  • VP 16-213
  • VP-16

Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888
  • A-861695.0

Active Comparator: Arm B (placebo)
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.
Drug: Cisplatin
Given IV
Other Names:
  • Cisdiaminedichloroplatinum
  • Cis -diaminedichloroplatinum (II)
  • diaminedichloroplatinum
  • Platinol -AQ
  • Cis-platinum
  • P latinol
  • platinum
  • DDP
  • CDDP
  • DACP
  • NSC 119875

Drug: Etoposide
Given IV
Other Names:
  • Epipodophyllotoxin
  • EPEG
  • Vepesid
  • VP 16-213
  • VP-16

Drug: Placebo
placebo of Veliparib
Other Name: placebo therapy




Primary Outcome Measures :
  1. Recommended Phase II Dose (Phase I) [ Time Frame: assessed for a maximum of cycle 1 ]
    dose of veliparib which was deemed to be the recommended phase II dose to be administered in the combination with CE for the phase II clinical trial

  2. Progression Free Survival (Phase II) [ Time Frame: Assessed every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration until the date of first documented progression or death. No specific requirements if patient is > 3 years from registration ]
    Profession free survival (PFS) is defined as time from randomization to date of disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date they were last known to be alive and progression-free. Tumor response was evaluated via Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, and progression was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Median PFS was estimated using the Kaplan-Meier method.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Assessed every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration until the date of death. No specific requirements if patient is > 3 years from registration ]
    Overall survival (OS) is defined as time from randomization to death from any cause. Median OS was estimated using the Kaplan-Meier method.

  2. Overall Response Rate (ORR) [ Time Frame: assessed every 6 weeks while on study, then every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration. ]
    Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Complete response (CR) was defined as disappearance of all target lesions. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Overall response rate= (CR+PR)/all eligible and treated patients


Other Outcome Measures:
  1. Neurotoxicity Total Score Change Between Baseline and 3 Months After Treatment Start [ Time Frame: assessed at baseline and 3 months after treatment initiation ]
    Neurotoxicity total score was measured by the 11 items in the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire. Each item was scored from 0-4. The severity of neurotoxicity was measured by the total score of the 11 items, ranged from 0 to 44. Lower values of the FACT/GOG-Ntx neurotoxicity total score indicate higher neurotoxicity.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

PHASE I

Inclusion Criteria (phase I):

  • 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 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

Exclusion Criteria (phase I):

  • Patients have active seizure(s) or history of seizure(s)
  • Patients 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

Inclusion Criteria (phase II):

  • 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) with the current month counted as month 1
  • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
  • 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
  • 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
  • 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)
  • AST (SGOT) and ALT (SGPT) =< 3 times institutional ULN (=< 5 times if 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 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
  • Patient must be able to swallow pills
  • Patients may not be receiving any other investigational agents while on study

Exclusion Criteria (phase II):

  • Patients with CNS metastases or a history of CNS metastases are ineligible
  • Patients have history of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib or other agents used in the study
  • Patients have active seizure(s) or history of seizure(s)
  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01642251


  Show 428 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Taofeek Owonikoko ECOG-ACRIN Cancer Research Group

Publications of Results:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01642251     History of Changes
Other Study ID Numbers: NCI-2012-01985
E2511 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
U10CA180820 ( U.S. NIH Grant/Contract )
U10CA021115 ( U.S. NIH Grant/Contract )
U24CA196172 ( U.S. NIH Grant/Contract )
First Posted: July 17, 2012    Key Record Dates
Results First Posted: February 5, 2019
Last Update Posted: February 5, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Cancer Institute (NCI):
Veliparib
Small cell lung cancer
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Neuroendocrine
Carcinoma, Small Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Cisplatin
Etoposide
Etoposide phosphate
Veliparib
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action