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Non-small Cell Lung Cancer Stage IIIPhase 1/2NCT02412371

A Study Evaluating the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Adults With Stage III Non-Small Cell Lung Cancer (NSCLC)

A Phase 1/2 study testing Paclitaxel, Carboplatin and Veliparib in people with Non-small Cell Lung Cancer Stage III, run by AbbVie at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study seeks to establish the recommended Phase 2 dose (RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based chemoradiotherapy (CRT) and consolidation with paclitaxel/carboplatin-based chemotherapy (Phase 1 portion), and to assess whether the addition of oral veliparib versus placebo to… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer Stage III
What is being tested?
Paclitaxel, Carboplatin and Veliparib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
12 sitesUnited States
Study dates
30 Apr 2015to 5 Aug 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants with histologically or cytologically confirmed Stage III non-small cell lung cancer (NSCLC).
  • Participants in the randomized portion of the study must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 criteria.
  • Participants must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) < 35%.
  • Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 - 1.
  • Participant must have adequate hematologic, renal, hepatic, and lung function.
  • Participant must consent to provide archived tissue or cytology sample of NSCLC lesion for analysis.

Who cannot join

  • Participants with prior chemotherapy or radiotherapy (RT) for current NSCLC. Participants curatively treated for past early stage NSCLC greater than 3 years ago may be included.
  • Participants with prior exposure to poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors.
  • Participants with known hypersensitivity to carboplatin, paclitaxel, or formulations containing polyethoxylated castor oil (Cremophor).
  • Participants with prior mediastinal or thoracic radiotherapy. Prior tangential radiotherapy to prior breast cancer is acceptable.
  • Participants with major surgery in the 4 weeks prior to randomization (Video-assisted thoracoscopic surgery (VATS) and/or mediastinoscopy is not considered major surgery).
  • Participants with a previous or concurrent malignancy except for treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient received potentially curative treatment and has been disease-free for 3 years or is considered cured by the investigator if has been disease-free for less than 3 years.
  • Participant is pregnant or lactating.
  • Participant with sensory peripheral neuropathy of ≥ Grade 2 at baseline, unable to swallow medication, or participants with prior history of seizure within the prior 12 months.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Univ Maryland School Medicine /ID# 132944

    Baltimore, Maryland, 21201

  • Dana-Farber Cancer Institute /ID# 133494

    Boston, Massachusetts, 02215

  • Unc /Id# 133496

    Chapel Hill, North Carolina, 27599

  • University of Virginia /ID# 133495

    Charlottesville, Virginia, 22908

  • University of Chicago /ID# 133828

    Chicago, Illinois, 60637-1443

  • Duke University Medical Center /ID# 133497

    Durham, North Carolina, 27710-3000

  • Ucsd /Id# 133037

    La Jolla, California, 92093

  • Christiana Care Health Service /ID# 133486

    Newark, Delaware, 19713

  • Rhode Island Hospital /ID# 133493

    Providence, Rhode Island, 02903

  • The Miriam Hospital /ID# 133910

    Providence, Rhode Island, 02906

  • SUNY Upstate Medical University - Downtown /ID# 133492

    Syracuse, New York, 13210

  • Wake Forest Univ HS /ID# 134608

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Subjects With Stage III Non-Small Cell Lung Cancer (NSCLC)

This study seeks to establish

  • the recommended Phase 2 dose (RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based chemoradiotherapy (CRT) and consolidation with paclitaxel/carboplatin-based chemotherapy (Phase 1 portion), and
  • to assess whether the addition of oral veliparib versus placebo to paclitaxel/carboplatin-based chemoradiotherapy with paclitaxel/carboplatin consolidation will improve progression-free survival (PFS) in adults with Stage III non-small cell lung cancer (Phase 2 portion).

A strategy decision was made not to proceed to Phase 2 portion of this study due to change in standard of care.

Read the detailed description

This was to be a 2-phase study consisting of

  1. A Phase 1, dose escalation study of veliparib to determine a RPTD for combination with concurrent paclitaxel/carboplatin-based CRT and paclitaxel/carboplatin-based consolidation chemotherapy; followed by
  2. A Phase 2, randomized, double-blinded study to determine whether veliparib improved outcome relative to placebo when added to paclitaxel/carboplatin based CRT followed by consolidation paclitaxel/carboplatin in adults with previously untreated Stage III NSCLC.

In the dose escalation phase (Phase 1) of the study participants will be assigned to ascending doses of veliparib in combination with carboplatin, paclitaxel, and thoracic radiotherapy for 7 weeks following a traditional "3 + 3" design. The first cohort of at least 3 - 6 participants will receive veliparib 60 mg twice a day (BID) throughout CRT. Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new dosing cohort is opened or until the RPTD is identified. Participants will also receive a consolidation dose of veliparib of 120 mg BID + carboplatin and paclitaxel for up to two 21-day cycles. Once the concurrent CRT RPTD is identified, an additional cohort will be enrolled to explore the tolerability of a consolidation dose of veliparib at 240 mg BID + carboplatin + paclitaxel for up to two 21-day cycles.

Following the dose escalation portion of the study, the RPTD will be determined by the sponsor and the Phase 2 portion of the study will begin with patient randomization in a 1:1:1 ratio to concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/veliparib, concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/placebo, or concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo. Randomization will be stratified by tumor volume (≤ 90 versus > 90 cm³) and smoking history (current smoker versus former smoker versus never smoked).

Phase 2 was not carried out since during the study there was a change in standard of care for patients with newly diagnosed, unresectable Stage III NSCLC.

Being tested
Paclitaxel, Placebo for Veliparib, Carboplatin, Veliparib, Radiotherapy
Keywords
veliparib, PARP inhibitor, ABT-888, first line, previously untreated, stage III, non-small cell lung cancer, radiotherapy, paclitaxel, carboplatin
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PaclitaxelDrug

    Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)

  • Placebo for VeliparibDrug

    Capsule for oral administration

  • CarboplatinDrug

    Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)

  • VeliparibDrug

    Also called ABT-888

    Capsule for oral administration

  • RadiotherapyRadiation

    Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks

Study groups in NCT02412371
Study groupRoleWhat they receive
Phase 1: Veliparib + Carboplatin + Paclitaxel + RadiotherapyExperimentalParticipants in Phase 1 will be sequentially assigned to ascending dose levels of 60 mg, 80 mg, 120 mg, 200 mg, and 240 mg of twice daily (BID) veliparib in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Veliparib; Radiation: Radiotherapy
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/VeliparibExperimentalParticipants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Receives: Drug: Paclitaxel; Drug: Carboplatin; Drug: Veliparib; Radiation: Radiotherapy
Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/PlaceboExperimentalParticipants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Receives: Drug: Paclitaxel; Drug: Placebo for Veliparib; Drug: Carboplatin; Drug: Veliparib; Radiation: Radiotherapy
Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/PlaceboActive comparatorParticipants will receive placebo to veliparib with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle.
Receives: Drug: Paclitaxel; Drug: Placebo for Veliparib; Drug: Carboplatin; Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose-limiting Toxicities (DLTs)

    DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

    • Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity
    • Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of >3 weeks or early discontinuation (DC) of RT (total dose <50 Gy)
    • ≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of >7 days despite medical management, neutropenia for >7 days or neutropenic fever or thrombocytopenia
    • ≥G2 seizure
    • G4 diarrhea or nausea/vomiting despite antiemetic therapy for >48 hours
    • Any other toxicity resulting in delay in RT, CT or veliparib >14 days or early DC of RT
    • Other nonhematologic toxicities ≥G3, except anorexia, fatigue, G3 infection, G3 aspartate/alanine transferase (AST/ALT) elevations ≤7 days, infusion reactions, G3/4 lymphopenia or electrolyte abnormalities corrected to ≤G2 in <48 hours

    Measured: For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy.

Secondary outcomes (1)

  1. Objective Response Rate

    Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders.

    Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis).

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Response must have been confirmed 4 weeks after the first documentation.

    Measured: Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2015 (estimated)
  2. Study start30 Apr 2015
  3. Primary completion5 Aug 2019
  4. Study completion5 Aug 2019

Why it stopped: Phase 2 was not conducted due to a change in the standard of care for newly diagnosed, unresectable Stage III NSCLC

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
In the dose escalation phase (Phase 1) of the study participants will be enrolled sequentially to receive ascending dose of veliparib in combination with carboplatin + paclitaxel + thoracic radiotherapy. In the Phase 2 portion of the study participants were to be randomized in a 1:1:1 ratio to one of three treatment arms.
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02412371
Sponsor's protocol ID
M14-360
Other IDs
2016-001659-32, 2016
Status last verified
Jul 2020
First submitted
6 Nov 2014
Last updated
22 Jul 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Paclitaxel, Carboplatin and Veliparib in people with Non-small Cell Lung Cancer Stage III, run by AbbVie at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02412371.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2020; AzTrials last refreshed its copy on 6 Nov 2026.

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