Dose Escalation and Double-blind Study of Veliparib in Combination With Carboplatin and Etoposide in Treatment-naive Extensive Stage Disease Small Cell Lung Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02289690
• Date of registration: 10/11/2014
• Prospective Registration: No
• Primary sponsor: AbbVie
• Public title: Dose Escalation and Double-blind Study of Veliparib in Combination With Carboplatin and Etoposide in Treatment-naive Extensive Stage Disease Small Cell Lung Cancer
• Scientific title: A Phase 1 Dose Escalation and Phase 2 Randomized Double-Blind Study of Veliparib in Combination With Carboplatin and Etoposide as a Therapy of Treatment-Naïve Extensive Stage Disease Small Cell Lung Cancer
• Date of first enrolment: October 13, 2014
• Target sample size: 221
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02289690
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, Czechia, France, Hungary, Korea, Republic of, Netherlands, Romania, Russian Federation, Spain, United States

Contacts

• Name: AbbVie Inc.
• Affiliation: AbbVie

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Subject with histologically or cytologically confirmed extensive-stage disease SCLC
which is newly diagnosed and chemotherapy naive

2. Phase 1 ONLY: histologically or cytologically confirmed advanced/metastatic solid
tumors for which carboplatin/etoposide treatment is considered appropriate.

3. Subject in Phase 2 only: must have measurable disease per RECIST 1.1.

4. Subjects with ED SCLC must consent to provide available archived formalin fixed
paraffin embedded (FFPE) tissue sample of SCLC lesion (primary or metastatic) for
central review and biomarker analysis.

5. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.

6. Subject must have adequate hematologic, renal and hepatic function.

Exclusion Criteria:

1. Phase 1 ONLY: Subject has had any prior anti-cancer therapy other than:

Hormonal, non-myelosuppressive, biologic, targeted, or immune therapy (must be
completed = 4 weeks prior to Cycle 1 Day -2).

One line of cytotoxic chemotherapy (must be completed = 4 weeks prior to Cycle 1 Day
-2).

Adjuvant/neoadjuvant radiotherapy (must be completed = 12 months prior to Cycle 1 Day
-2, with field not involving > 10% of bone marrow reserve).

2. Phase 2 ONLY: Subject has had any prior chemotherapy, radiotherapy, investigational
anti-cancer agents or biologic therapy for the disease under study. Single non-target
lesion irradiation with intent of symptom palliation is allowed if = 4 weeks prior
Cycle 1 Day -2.

3. Subject has current central nervous system (CNS) or leptomeningeal metastases or
history of CNS or leptomeningeal metastases.

4. Subject has a history of seizures within 12 months of Cycle 1 Day-2 or diagnosed
neurological condition placing subject at the increased risk of seizures.

5. Subject has received anti-cancer Chinese medicine or anti-cancer herbal remedies
within 14 days prior to Cycle 1 Day-2.

6. Subject has had major surgery within 6 weeks prior to Cycle 1 Day-2 (subjects must
have completely recovered from any previous surgery prior Cycle 1 Day-2).

7. Subject has clinically significant and uncontrolled major medical condition(s)
including but not limited to:

- Uncontrolled nausea/vomiting/diarrhea;

- Active uncontrolled infection;

- History of hepatitis B (HBV) with surface antigen (HBsAg) positivity within 3
months prior to the date of informed consent for this study (if no test has been
performed within 3 months, it must be done at screening);

- History of hepatitis C (HCV) with HCV ribonucleic acid (RNA) positivity within 3
months prior to the date of informed consent for this study (if no test has been
performed within 3 months it must be done at screening);

- Symptomatic congestive heart failure (Yew York Heart Association [NYHA] class =
II);

- Unstable angina pectoris or cardiac arrhythmia (except atrial fibrillation);

- Psychiatric illness/social situation that would limit compliance with study
requirements;

- Any other medical condition, which in the opinion of the Investigator, places the
subject at an unacceptably high risk for toxicities.

8. The subject has a history of another active cancer within the past 3 years except
cervical cancer in situ, in situ carcinoma of the bladder, squamous or basal cell
carcinoma of the skin or another in situ cancer that is considered cured by the
investigator (e.g., in situ prostate cancer, breast DCIS).



Age minimum: 18 Years
Age maximum: 99 Years
Gender: All

Health Condition(s) or Problem(s) studied

Small Cell Lung Cancer

Intervention(s)

Drug: Carboplatin

Drug: Veliparib

Drug: Etoposide

Drug: Placebo

Primary Outcome(s)

Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-8]) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib [Time Frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose]

Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-8]) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) [Time Frame: Cycle 1 Day -2 to pre-dose on Cycle 2 Day 1 (23 days)]

Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib [Time Frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose]

Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib [Time Frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose]

Phase 2: Progression-free Survival [Time Frame: From randomization up to the date the 126th PFS event was reached; Median time on follow-up was 7.3, 7.1, and 8.9 months in each treatment group respectively.]

Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib [Time Frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose]

Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib [Time Frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose]

Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib [Time Frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose]

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib [Time Frame: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.]

Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib [Time Frame: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose]

Secondary Outcome(s)

Phase 1: Number of Participants With Adverse Events [Time Frame: From first dose of any study drug to 30 days after the last dose; the median duration of treatment with veliparib across all groups in Phase 1 was 127.5 days.]

Phase 2: Objective Response Rate [Time Frame: Tumor assessments were performed every 6 weeks for the first 30 weeks and every 9 weeks thereafter until disease progression; median time on follow-up was 7.3, 7.1, and 8.9 months in each group respectively.]

Phase 2: Overall Survival [Time Frame: From randomization until the end of study; median time on follow-up was 10.0, 8.6, and 11.7 months in each treatment group respectively.]

Secondary ID(s)

2014-001764-35

M14-361

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 14/05/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02289690