A multi center study to assess the safety and efficacy of nab-paclitaxel with CC-486 and nab-paclitaxel alone as 2nd line treatment in subjects with advanced nonsquamous NSCLC

• Register: EUCTR
• Last refreshed on: 26 September 2023
• Main ID: EUCTR2014-001105-41-ES
• Date of registration: 03/10/2014
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: A multi center study to assess the safety and efficacy of nab-paclitaxel with CC-486 and nab-paclitaxel alone as 2nd line treatment in subjects with advanced nonsquamous NSCLC
• Scientific title: A Phase 2, randomized, open-label, multicenter study to assess safety and efficacy of nab-paclitaxel (ABI-007) with epigenetic modifying therapy of CC-486, and nab-paclitaxel monotherapy as second-line treatment in subjects with advanced nonsquamous non-small cell lung cancer (NSCLC): ABOUND.2L - ABOUND.2L
• Date of first enrolment: 25/11/2014
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001105-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, France, Germany, Italy, Netherlands, Spain, United States

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must satisfy the following criteria to be randomized in the study:
1.Age ? 18 years the time of signing the Informed Consent Form (ICF).
2.Understand and voluntarily provide written informed consent prior to the conduct of any study related assessments/procedures.
3.Able to adhere to the study visit schedule and other protocol requirements
4.Histologically or cytologically confirmed advanced nonsquamous NSCLC.
5.No other current active malignancy requiring anticancer therapy.
6.Radiographically documented measurable disease (defined by the presence of ? 1 radiographically documented measurable lesion).
7.One prior platinum-containing chemotherapy for the treatment of advanced disease.
8.Absolute neutrophil count (ANC) ? 1500 cells/mm3.
9.Platelets ? 100,000 cells/mm3.
10.Hemoglobin (Hgb) ? 9 g/dL.
11.Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ? 2.5 × upper limit of normal range (ULN) or ? 5.0 × ULN if liver metastases.
12.Total bilirubin ? 1.5 ULN (unless there is a known history of Gilberts Syndrome).
13.Serum creatinine ? 1.5 x ULN, or calculated creatinine clearance ? 60 mL/min (if renal impairment is suspected 24-hour urine collection for measurement is required).
14.Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
15.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:
a.Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 hours prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.
b.Either commit to true abstinence* from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 3 months after discontinuation of study therapy.
Male subjects must:
a.Practice true abstinence* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following IP discontinuation, even if he has undergone a successful vasectomy.
16.Females must abstain from breastfeeding during study participation and 3 months after IP discontinuation.

*True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion criteria:
The presence of any of the following will exclude a subject from enrollment:
1.Squamous cell NSCLC.
2.Prior taxane therapy.
3.Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if asymptomatic and clinically stable for at least 8 weeks following completion of therapy). MRI of the brain (or CT scan w/contrast) is preferred.
4.Only evidence of disease is non-measurable.
5.Known EGFR mutation.
6.Known EML4-ALK mutation.
7.Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).
8.Venous thromboembolism within 1 month prior to Cycle 1 Day 1.
9.Current congestive heart failure (New York Heart Association Class II-IV).
10.History of the following within 6 months prior to Cycle 1 Day 1: 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 electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
11.Known hepatitis B or C virus (HBV/HCV) infection, known history of human immunodeficiency virus (HIV) infection, or receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications.
12.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.
13.History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis.
14.Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical management.
15.Treatment with any investigational product within 28 days prior to signing the ICF.
16.History of or suspected allergy to nab-paclitaxel, azacitidine, human albumin or mannitol.
17.Currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices.
18.Any other clinically significant medical condition, psychiatric illness, and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol or which, in the views of investigator, preclude combination chemotherapy.
19.Any other malignancy within 5 years prior to randomization, or advanced malignant hepatic tumors, with the exception of adequately treated squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All treatment of which should have been completed 6 months prior to signing ICF).
20.Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
21.Any medical condition that confounds the ability to interpret data from the study.
22.Pregnant or breastfeeding females.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced nonsquamous non-small cell lung cancer (NSCLC).
MedDRA version: 17.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Abraxane
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Current Sponsor code: ABI-007
Other descriptive name: -
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Product Name: Azacitidina oral
Product Code: CC-486
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AZACITIDINA
CAS Number: 320-67-2
Current Sponsor code: -
Other descriptive name: -
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To assess the efficacy of nab-paclitaxel administered intravenously (IV) on Days 8 and 15 with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as second-line treatment for advanced nonsquamous NSCLC, and the relative efficacy of these two treatment regimens.

Primary end point(s): Progression free survival

Secondary Objective: To evaluate the safety and tolerability of nab-paclitaxel administered IV on Days 8 and 15 in combination with epigenetic modifying therapy of CC-486 once daily (QD) on Days 1 to 14 every 21 days, and nab-paclitaxel monotherapy administered IV on Days 1 and 8 every 21 days as second-line treatment for advanced nonsquamous NSCLC.

Timepoint(s) of evaluation of this end point: The time from the date of randomization to the date of disease progression or death (any cause) on or prior to the data cutoff date for analyses, whichever occurs first.

Secondary Outcome(s)

Secondary end point(s): Efficacy
- Disease control rate
- Overall response rate
- Overall survival

Safety
- The type, frequency, and severity of AEs and SAEs graded using National Cancer
Institute Common Terminology Criteria for Adverse Events (Version 4.0).
- Discontinuation rate
- The median dose intensity
- The incidence of dose reduction

Timepoint(s) of evaluation of this end point: Disease control rate, OS, and ORR will be evaluated within each treatment arm and between the treatment arms at the time of the final analysis of the PFS endpoint when approximately 120 PFS events have been observed.

Secondary ID(s)

ABI-007-NSCL-006

Source(s) of Monetary Support

Celgene Corporation

Ethics review

Status: Approved
Approval date: 14/11/2014
Contact: