Phase II Safety and Tolerability Trial With Nab-Paclitaxel Plus Carboplatin Followed by Nab-Paclitaxel for First Line Treatment of NSCLC Subjects With ECOG PS 2

NCT02289456 | Completed Phase 2 Results DMC

• 1 other identifier: ABI-007-NSCL-004
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 8

Brief Summary

4 cycles of induction treatment with nab-paclitaxel and carboplatin followed by nab-paclitaxel monotherapy for those subjects who are progression free at the end of 4 cycles.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Phase II, LOCALLY ADVANCED OR METASTATIC NON SMALL; CELL LUNG CANCER (NSCLC) AND AN; EASTERN COOPERATIVE ONCOLOGY GROUP; PERFORMANCE STATUS OF 2; (ABOUND.PS2); LOCALLY ADVANCED OR METASTATIC NON SMALL; CELL LUNG CANCER (NSCLC) SUBJECTS THAT AE NOT CANDIDATES FOR RADIATION OR CURATIVE SURGERY

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Discontinued Study Treatment During the Induction Period Due to Treatment Emergent Adverse Events (TEAEs).

  Treatment-emergent adverse events were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. A participant met the primary endpoint if: an AE was the reason for discontinuation as recorded in the electronic Case Report Form (eCRF) and the participant had no doses administered beyond Cycle 4. 95% confidence interval for the percentage was calculated using the Clopper Pearson method.

  From date of the first dose of IP until 28 days after the last dose of IP during induction and SAEs made known to the investigator any time thereafter that are suspected of being related to IP; maximum treatment duration during induction was 3.9 months

Secondary Outcomes (11)

• Percentage of Participants Who Discontinued Study Treatment During the Induction Period (Discontinuation Rate)

  From date of the first dose of IP until 28 days after the last dose of IP during induction and SAEs made known to the investigator any time thereafter that are suspected of being related to IP; maximum treatment duration during induction was 3.9 months

• Dose Intensity of Nab-Paclitaxel During the Entire Study

  From Day 1 of study treatment to end of study treatment; maximum treatment duration on study was 14.1 months

• Dose Intensity of Carboplatin During the Entire Study

  From Day 1 of study treatment to end of study treatment; maximum treatment duration on study was 14.1 months

• Percentage of Participants With Dose Reductions During the Entire Study

  From day 1 of IP until 28 days after the last dose of IP; maximum treatment duration was 14.1 months during the entire study

• Kaplan Meier Estimate of Progression-Free Survival (PFS)

  From Day 1 of study drug treatment to the date of disease progression; up to the clinical cut-off date of 24 February 2017; maximum treatment duration on study was 14.1 months

Other Outcomes (1)

• Percentage of Protocol Dose

  From Day 1 of study drug treatment to end of study drug treatment; up to clinical data cut-off date of 24 February 2017; ; maximum treatment duration was 14.1 months.

Study Arms (1)

nab-Paclitaxel

EXPERIMENTAL

nab-Paclitaxel 100 mg/m2 intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle • Carboplatin AUC = 5 mg\*min/mL IV on Day 1 of each 21-day cycle after completion of nab-paclitaxel infusion.

Drug: nab-Paclitaxel; Drug: Carboplatin

Interventions

nab-Paclitaxel DRUG

Also known as: Abraxane

nab-Paclitaxel

Carboplatin DRUG

Also known as: Paraplatin

nab-Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General and Demographics
• Age ≥ 18 years of age at the time of signing the Informed Consent Form.
• Understand and voluntarily provide written consent to the Informed Consent Form prior to conducting any study related assessments/procedures.
• Able to adhere to the study visit schedule and other protocol requirements. Disease Specific
• Histologically or cytologically confirmed Stage IIIB or IV Non-Small Cell Lung Cancer.
• Radiographically documented measurable disease at study entry per response evaluation criteria in solid tumours ( RECIST) v1.1.
• No prior anti-cancer therapy for the treatment of metastatic disease at the time of signing the ICF. Adjuvant treatment is permitted providing cytotoxic chemotherapy was completed 12 months prior to signing the ICF and without disease recurrence.
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.
• Platelets ≥ 100,000 cells/mm3.
• Hemoglobin (Hgb) ≥ 9 g/dL.
• Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase \[SGOT\]), alanine transaminase (ALT/serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × upper limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.
• Total bilirubin ≤ 1.5 × ULN except in cases of Gilbert's disease and liver metastases.
• Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance ≥ 40 mL/min (if renal impairment is suspected 24-hour urine collection for measurement is required).
• Eastern Cooperative Oncology Group Performance Status 2.
• Females of childbearing potential \[defined as a sexually mature woman who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months)\] must:

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if treated and stable and off therapy for at least 21days prior to signing ICF). MRI of the brain (or CT scan w/contrast) is preferred for diagnosis.
• History of leptomeningeal disease.
• Only evidence of disease is non-measurable.
• Pre-existing peripheral neuropathy of Grade 2, 3, or 4 (per Criteria for Adverse Events (CTCAE) v4.0).
• Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting investigational product (IP), and/or from whom ≥ 30% of the bone marrow was irradiated. Prior radiation therapy to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.
• Venous thromboembolism within 1 month prior to signing ICF.
• Current congestive heart failure (New York Heart Association Class II-IV).
• History of the following within 6 months prior to first administration of investigational product: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant ECG abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
• Subject has a known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications.
• Subject has an active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
• History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis.
• Treatment with any investigational product within 28 days prior to signing the ICF.
• History of or suspected allergy to nab-paclitaxel, carboplatin and human albumin or any other platinum-based therapy.
• Currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices.

Sponsors & Collaborators

• Celgene: lead

Study Sites (8)

University Cancer Institute

Boynton Beach, Florida, 33426, United States

Location

Ochsner Clinic Nephrology

New Orleans, Louisiana, 70121, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

University of RochesterJames P. Wilmont Cancer Center

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes

Limitations and Caveats

Due to slower than expected enrollment, Celgene elected to end enrollment. The decision was not based on safety concerns; those enrolled continued treatment and survival follow-up until 24 February 2017.

Results Point of Contact

• Title: Anne McClain, Senior Manager
• Organization: Celgene Corporation

ClinicalTrialDisclosure@celgene.com

888-260-1599

Study Officials

• Francois Lafleur, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: November 13, 2014
• Study Start: April 28, 2015
• Primary Completion: February 22, 2017
• Study Completion: February 22, 2017
• Last Updated: December 7, 2018
• Results First Posted: April 24, 2018

Record last verified: 2018-12

Locations

US (8)