E2511: 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 ID
STU 102012-035

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
Laurin Priddy
214-648-1688
laurin.loudat@utsouthwestern.edu

Principal Investigator
David Gerber

Summary

This randomized phase i/ii trial studies the side effects and the best dose of veliparib giving together with cisplatin and etoposide and to see how well it works in treating patients with extensive stage small cell lung cancer or metastatic large cell neuroendocrine non-small cell lung cancer.

Phase i Schema will include:

arm a:
Veliparib 60mg po bid3 Days 1-7
etoposide 100mg/m2 in 500ml nS Days 1-3
Cisplatin 75 mg/m2 in 250ml nS Day 1
every cycle for 4 cycles

arm B:
Veliparib 100mg po bid3 Days 1-7
etoposide 100mg/m2 in 500ml nS Days 1-3
Cisplatin 75 mg/m2 in 250ml nS Day 1
every cycle for 4 cycles

arm C:
Veliparib 40mg po bid3 Days 1-7
etoposide 100mg/m2 in 500ml nS Days 1-3
Cisplatin 75 mg/m2 in 250ml nS Day 1
every cycle for 4 cycles

Phase ii Schema (Randomized) will include:

experimental arm (D):
* Veliparib pills (RP2D2) bid po Days 1-71
* etoposide 100 mg/m2 in 500 ml nS Days 1-3
* Cisplatin 75 mg/m2 in 250 ml nS Day 1
* every cycle for 4 cycles

Control arm (e):
* Placebo bid po Days 1-71
* etoposide 100 mg/m2 in 500 ml nS Days 1-3
* Cisplatin 75 mg/m2 in 250 ml Day 1
* every cycle for 4 cycles

Participant Eligibility

Inclusionary Criteria: Phase I: Registration to Arms A, B, or C


* Age > 18 years


* 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).


* Patients must have histologically or cytologically confirmed either: Extensive stage small cell lung cancer


* Stage IV (M1a or M1b according to AJCC Staging Manual, 7th edition) large cell neuroendocrine NSCLC
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-measureable disease based on RECIST 1.1 (see Section 6). Baseline measurements and evaluations of all sites of disease must be obtained < 4 weeks prior to registration.


* ECOG performance status 0 or 1


* Patients must have acceptable organ and marrow function as defined below (these must be obtained < 7 days prior to protocol registration):


* Absolute neutrophil count >1,500/mm3


* Platelets >=100,000/mm3


* Leukocytes >= 3000/mm3


* Hemoglobin >= 9 g/dL


* Total bilirubin <= 1.5 X institutional upper limit of normal (ULN)


* AST (SGOT) and ALT (SGPT) <= 3 X institutional upper limit of normal (ULN)

* (< 5 X if LFT elevations due to known liver metastases)


* Creatinine <= 1.5 X institutional upper limit of (ULN) normal OR creatinine clearance >= 60 mL/min/1.73m2 for patients with creatinine levels > 1.5 x institutional upper limit of normal (ULN).


* Patient must be able to swallow pills.


Inclusionary Criteria Phase II: Randomization (Arms D and E)


* Age > 18 years


* Women must not be pregnant or breastfeeding. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the agents used in this study, 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 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 (see Section 6).
Baseline measurements and evaluations of all sites of disease must be obtained < 4 weeks prior to registration.


* ECOG performance status 0 or 1


* Patients must have acceptable organ and marrow function as defined below (these must be obtained < 7 days prior to protocol randomization):


* Absolute neutrophil count >1,500/mm3


* Platelets >100,000/mm3


* Leukocytes > 3000/mm3


* Hemoglobin > 9 g/dL


* Total bilirubin <1.5 X institutional upper limit of normal (ULN)


* AST (SGOT) and ALT (SGPT) < 3 X institutional upper limit of normal (ULN)

* (< 5 X if LFT elevations due to known liver metastases)


* Creatinine < 1.5 X institutional upper limit of (ULN) normal OR creatinine clearance > 60 mL/min/1.73m2 for patients with creatinine levels > 1.5 x institutional upper limit of normal (ULN).


* Patient must be able to swallow pills