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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Extensive Stage Small Cell Lung Cancer, Large Cell Lung Cancer, Metastatic Carcinoma of Unknown Primary, Neuroendocrine Carcinoma, Newly Diagnosed Carcinoma of Unknown Primary

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Trial Information

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


PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose (RP2D) of veliparib to use in combination with
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,
randomized, double-blind 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 stratified according to gender (male vs female) and lactate
dehydrogenase (LDH) (=< ULN vs > ULN. 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.

Peripheral blood mononuclear cells and tumor tissue samples may be collected periodically
for correlative studies.

After completion of study treatment, patients are followed up periodically for 3 years.


Inclusion Criteria:



- Women must not be pregnant or breastfeeding

- All females of childbearing potential must have a blood test within 2 weeks prior to
registration 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) (Phase I and II)

- 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, or
bilateral or contralateral supraclavicular adenopathy

- 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) (Phase I only)

- Small cell carcinoma of unknown primary or extrapulmonary origin and must be a
candidate for systemic therapy (phase I only)

- 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)

- 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)

- 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 glutamic 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 (phase I and
II) or large cell neuroendocrine NSCLC (phase I only), or small cell carcinoma of
unknown primary or extrapulmonary origin (phase I only)

- 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 may not be receiving any other investigational agents while on study

- 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose of veliparib based on the incidence of dose-limiting toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Taofeek Owonikoko

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01985

NCT ID:

NCT01642251

Start Date:

September 2012

Completion Date:

Related Keywords:

  • Extensive Stage Small Cell Lung Cancer
  • Large Cell Lung Cancer
  • Metastatic Carcinoma of Unknown Primary
  • Neuroendocrine Carcinoma
  • Newly Diagnosed Carcinoma of Unknown Primary
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Small Cell Lung Carcinoma
  • Carcinoma, Neuroendocrine
  • Neoplasms, Unknown Primary

Name

Location

Johns Hopkins UniversityBaltimore, Maryland  21205
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283
Ingalls Memorial HospitalHarvey, Illinois  60426
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
Cancer Institute of New Jersey at HamiltonHamilton, New Jersey  08690
Paoli Memorial HospitalPaoli, Pennsylvania  19301-1792
Parkland Memorial HospitalDallas, Texas  75235
Bryn Mawr HospitalBryn Mawr, Pennsylvania  19010
Trinity Medical CenterMoline, Illinois  61265-1291
Emory UniversityAtlanta, Georgia  30322
University of Texas Southwestern Medical CenterDallas, Texas  
Lankenau HospitalWynnewood, Pennsylvania  19096
Penn State Milton S Hershey Medical CenterHershey, Pennsylvania  17033
Mainline Health CCOPWynnewood, Pennsylvania  19096
Eastern Cooperative Oncology GroupBoston, Massachusetts  02215