CompletedNCT02730247Updated Nov 19, 2020Results posted

Clinical Trial of the Safety and Efficacy of the Addition of Ramucirumab to Nab-paclitaxel in Previously Treated Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

A Phase 2 interventional study of ramucirumab and nab-paclitaxel in Non-small Cell Lung Cancer, sponsored by Liza Villaruz, MD. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-11-19.

Sponsored by Liza Villaruz, MD · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 7
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

The subjects who take part in this clinical research study have advanced non-small cell lung cancer (NSCLC) that has been previously treated with other drugs. If they join this study, they would receive ramucirumab (Cyramza ®) in combination with nab-paclitaxel (Abraxane®). Ramucirumab given with nab-paclitaxel is considered an investigational drug combination to use in this type of cancer because giving these two drugs together has not been approved by any regulatory authority like the US Food and Drug Administration (FDA) for NSCLC cancer. Ramucirumab works by slowing or stopping the growth of cancer cells. Nab-Paclitaxel works by blocking the ability of cancer cells to break down the internal 'skeleton' that allows them to divide and multiply. With the skeleton still in place, the cells cannot divide and they eventually die.

Read the detailed description

Ramucirumab is a human IgG1 (Immunoglobulin G) monoclonal antibody that targets the extracellular domain of VEGFR-2 (vascular endothelial growth factor receptor). A recent double-blind, placebo-controlled clinical trial evaluated the addition of ramucirumab to docetaxel compared with docetaxel and placebo in patients with Stage IV squamous and non-squamous NSCLC in the 2nd-line treatment setting. This study demonstrated a superior overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) with the combination therapy compared with docetaxel with placebo. This effect was seen across histologic subtypes, in the absence of excess toxicity in patients with squamous cell histology. This finding is intriguing, as prior study of bevacizumab in patients with NSCLC of squamous cell histology was associated with excess pulmonary hemorrhage. This provides the rationale for further investigation of ramucirumab in patients with squamous cell NSCLC.

nab-Paclitaxel is a formulation of paclitaxel complexed with albumin that is readily soluble in saline and allows administration of paclitaxel without the use of lipid-based solvents and the need for corticosteroid and antihistamine premedication. nab-Paclitaxel was approved for the 1st line treatment of NSCLC based on a trial which demonstrated a superior ORR with the addition of nab-paclitaxel to carboplatin compared with carboplatin/paclitaxel in patients with advanced and metastatic NSCLC, as well as prolonged PFS and OS without statistical significance. The subgroup analysis by tumor histology demonstrated a statistically significant advantage for nab-paclitaxel/carboplatin in terms of best overall response rate (41% vs 24%, p\<0.001), and numerically better PFS and OS in squamous NSCLC. [3]

This is a single-arm phase II clinical trial, in which patients with previously treated NSCLC will be treated with ramucirumab/nab-paclitaxel until disease progression, unacceptable treatment-related toxicity or withdrawal of consent with the primary endpoint of progression-free survival. A minimum of 40 patients with squamous cell histology will be required for determination of the co-primary endpoint. The investigators hypothesize that the addition of ramucirumab to nab-paclitaxel is well-tolerated and associated with a superior PFS compared with single agent taxane-based therapy.

Conditions studied

Non-small Cell Lung Cancer

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Keywords

ramucirumab
docetaxel

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 7 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

Liza Villaruz, MD is the lead sponsor of 5 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

All patients must have or meet the following:

Histologically or cytologically confirmed Stage IV (AJCC 7) non-small cell lung cancer.
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
Received at least one prior platinum-based chemotherapy for locally advanced or metastatic disease. Prior bevacizumab as 1st line and/or maintenance therapy is allowed. Prior nivolumab is allowed.
Age ≥18 years.
ECOG performance status ≤2
Life expectancy of greater than 12 weeks.
Adequate liver function
Adequate hematologic function
Not have cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) with a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.
Adequate renal function
Urinary protein of ≤1+ on dipstick or routine urinalysis (UA).
Adequate coagulation function. Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
Treated and clinically stable brain metastases are allowed.
Adequate contraceptive use.
\< Grade 2 pre-existing peripheral neuropathy.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Patients with previous intolerance to ramucirumab.
Patients who are receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ramucirumab or nab-paclitaxel.
Patients with untreated CNS metastases.
Patients with significant bleeding disorders, vasculitis, or who experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment.
History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to enrollment.
Any arterial thromboembolic events, within 6 months prior to enrollment.
History of uncontrolled hereditary or acquired thrombotic disorder.
Uncontrolled or poorly-controlled hypertension.
A serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment.
Major surgery within 28 days prior to enrollment, or subcutaneous venous access device placement within 7 days prior to enrollment.
Chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
Elective or planned major surgery scheduled during the course of the clinical trial.
Hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months prior to enrollment, or with central or cavitating lesions.
Radiologically documented evidence of major blood vessel invasion or encasement by cancer.
History of GI perforation and/or fistulae within 6 months prior to enrollment, or risk factors for perforation.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnancy
HIV-positive patients on combination antiretroviral therapy.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 7 participants (actual)

Study arms

Experimental
ramucirumab + nab-paclitaxel
Ramucirumab will be administered through a vein in the arm as a 60 minute infusion at a dose of 8 mg/kg on days 1 and 15 of a 28-day cycle. The nab-paclitaxel will be administered through a vein in the arm as a 30 minute infusion at a dose of 100 mg/m2 on days 1, 8 and 15 of a 28 day cycle.
Drug: ramucirumab · Drug: nab-paclitaxel

Interventions

Drugramucirumab
it is administered through a vein in the arm as a 60 minute infusion at a dose of 8 mg/kg on days 1 and 15 of a 28-day cycle.
Also known as: Cyramza
Drugnab-paclitaxel
it is administered through a vein in the arm as a 30 minute infusion at a dose of 100 mg/m2 on days 1, 8 and 15 of a 28 day cycle.
Also known as: Abraxane

What researchers measure

Primary outcomes

Progression-free Survival (PFS)
The duration of time from start of treatment to time of progression or death. Progression as defined by RECIST v1.1 for target lesions: Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Time frame: Up to 26 months
Worst Grade of Adverse Event Experienced
Percentage of patients that experienced Grade 3-5 adverse events as their highest Grade event, irrespective of relatedness to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events).
Time frame: Up to 26 months
Worst Grade of Adverse Event Experienced, at Least Possibly Related to Treatment
Percentage of patients who experienced Grade 2-5 adverse events as their highest Grade event, that were at least possibly related to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events).
Time frame: Up to 26 months
Worst Grade of Adverse Event Experienced, at Least Probably Related to Treatment
Percentage of patients who experienced Grade 0-4 adverse events as their highest Grade event, that were at least probably related to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events).
Time frame: Up to 26 months
Worst Grade of Adverse Event Experienced, Definitely Related to Treatment
Percentage of patients that experienced Grade 0-2 adverse events as their highest Grade event, that were definitely related to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events.
Time frame: Up to 26 months

Secondary outcomes

Best Overall Response
Median percentage of patients who experienced a best response of partial or complete response (PR + CR) / total number of patients (PR + CR + Stable Disease (SD) + Progressive Disease (PD)), per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm; appearance new lesions.
Time frame: Up to 26 months
Overall Survival (OS)
The duration of time from the start of treatment to death.
Time frame: Up to 26 months
Median EuroQol Five Dimension Questionnaire (EQ-5D-5L) Score
The EuroQol Five Dimension questionnaire (EQ-5D-5L) score is a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: level 0=no problems, level 1=slight problems, level 2=moderate problems, level 3=severe problems and level 4= extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. Data is presented as a health profile table reporting a proportion of reported problems for each level for each dimension and/or dichotomised levels - 'no problems' (i.e. level 1) and 'problems' (i.e. levels 2 to 5)
Time frame: Baseline through up to 26 months

Results

Posted Nov 19, 2020

Participant flow

Participant flow — Overall Study
Milestone	Ramucirumab + Nab-paclitaxel
Started	7
Completed	7
Not completed	0

Outcome measures

PrimaryProgression-free Survival (PFS)

The duration of time from start of treatment to time of progression or death. Progression as defined by RECIST v1.1 for target lesions: Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). For non-target lesions: Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

Time frame:: Up to 26 months
Reported as:: Median · months

Progression-free Survival (PFS)
months	Ramucirumab + Nab-paclitaxel
Progression-free Survival (PFS)	8.16 (3.68 to NA)

PrimaryWorst Grade of Adverse Event Experienced

Percentage of patients that experienced Grade 3-5 adverse events as their highest Grade event, irrespective of relatedness to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events).

Time frame:: Up to 26 months
Reported as:: Number · percentage of participants

Worst Grade of Adverse Event Experienced
percentage of participants	Ramucirumab + Nab-paclitaxel
Grade 3 adverse event	57.1 (20.0 to 87.6)
Grade 4 adverse event	28.6 (6.2 to 70.7)
Grade 5 adverse event	14.3 (1.8 to 59.7)

PrimaryWorst Grade of Adverse Event Experienced, at Least Possibly Related to Treatment

Percentage of patients who experienced Grade 2-5 adverse events as their highest Grade event, that were at least possibly related to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events).

Time frame:: Up to 26 months
Reported as:: Number · percentage of participants

Worst Grade of Adverse Event Experienced, at Least Possibly Related to Treatment
percentage of participants	Ramucirumab + Nab-paclitaxel
Grade 2	14.3 (1.5 to 64.8)
Grade 3	42.9 (10.5 to 82.8)
Grade 4	28.6 (5.2 to 74.6)
Grade 5	14.3 (1.5 to 64.8)

PrimaryWorst Grade of Adverse Event Experienced, at Least Probably Related to Treatment

Percentage of patients who experienced Grade 0-4 adverse events as their highest Grade event, that were at least probably related to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events).

Time frame:: Up to 26 months
Reported as:: Number · percentage of participants

Worst Grade of Adverse Event Experienced, at Least Probably Related to Treatment
percentage of participants	Ramucirumab + Nab-paclitaxel
Grade 0	14.3 (1.3 to 68.4)
Grade 1	28.6 (4.5 to 77.3)
Grade 2	28.6 (4.5 to 77.3)
Grade 3	14.3 (1.3 to 68.4)
Grade 4	14.3 (1.3 to 68.4)

PrimaryWorst Grade of Adverse Event Experienced, Definitely Related to Treatment

Percentage of patients that experienced Grade 0-2 adverse events as their highest Grade event, that were definitely related to treatment, per NCI CTCAE v2.0 (National Cancer Institute Common Terminology Criteria for Adverse Events.

Time frame:: Up to 26 months
Reported as:: Number · proportion of participants

Worst Grade of Adverse Event Experienced, Definitely Related to Treatment
proportion of participants	Ramucirumab + Nab-paclitaxel
Grade 0	71.4 (29.3 to 93.8)
Grade 1	14.3 (1.8 to 59.7)
Grade 2	14.3 (1.8 to 59.7)

SecondaryBest Overall Response

Median percentage of patients who experienced a best response of partial or complete response (PR + CR) / total number of patients (PR + CR + Stable Disease (SD) + Progressive Disease (PD)), per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm; appearance new lesions.

Time frame:: Up to 26 months
Reported as:: Median · percentage of participants

Best Overall Response
percentage of participants	Ramucirumab + Nab-paclitaxel
Best Response - Stable Disease	67.7 (22.3 to 95.7)
Best Response - Partial Response	33.3 (4.3 to 77.8)

SecondaryOverall Survival (OS)

The duration of time from the start of treatment to death.

Time frame:: Up to 26 months
Reported as:: Median · months

Overall Survival (OS)
months	Ramucirumab + Nab-paclitaxel
Overall Survival (OS)	7.42 (3.48 to NA)

SecondaryMedian EuroQol Five Dimension Questionnaire (EQ-5D-5L) Score

The EuroQol Five Dimension questionnaire (EQ-5D-5L) score is a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: level 0=no problems, level 1=slight problems, level 2=moderate problems, level 3=severe problems and level 4= extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. Data is presented as a health profile table reporting a proportion of reported problems for each level for each dimension and/or dichotomised levels - 'no problems' (i.e. level 1) and 'problems' (i.e. levels 2 to 5)

Time frame:: Baseline through up to 26 months
Reported as:: Median · EQ-5D-5L score

Median EuroQol Five Dimension Questionnaire (EQ-5D-5L) Score
EQ-5D-5L score	Ramucirumab + Nab-paclitaxel
Walking	1 (0 to 2)
Dressing	1 (0 to 2)
Active	1 (0 to 4)
Pain	1 (0 to 4)
Anxious	1 (0 to 3)

Adverse events

Collected over Up to 26 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Ramucirumab + Nab-paclitaxel	5/7 (71.4%)	7/7 (100%)	7/7 (100%)

Most frequent serious events

Showing 10 of 14

Most frequent serious events
Event	Ramucirumab + Nab-paclitaxel
Lymphocyte count decreasedInvestigations	3/7
Neutrophil count decreasedInvestigations	3/7
HyponatremiaMetabolism and nutrition disorders	2/7
White blood cell decreasedInvestigations	2/7
AnemiaBlood and lymphatic system disorders	1/7
Cardiac arrestCardiac disorders	1/7
DyspneaRespiratory, thoracic and mediastinal disorders	1/7
Febrile neutropeniaBlood and lymphatic system disorders	1/7
HypertensionVascular disorders	1/7
HypoalbuminemiaMetabolism and nutrition disorders	1/7

Most frequent other events

Showing 10 of 65

Most frequent other events
Event	Ramucirumab + Nab-paclitaxel
AnemiaBlood and lymphatic system disorders	6/7
HyponatremiaMetabolism and nutrition disorders	6/7
FatigueGeneral disorders	5/7
HypoalbuminemiaMetabolism and nutrition disorders	5/7
Neutrophil count decreasedInvestigations	5/7
AnorexiaMetabolism and nutrition disorders	4/7
DyspneaRespiratory, thoracic and mediastinal disorders	4/7
HypophosphatemiaMetabolism and nutrition disorders	4/7
ProteinuriaRenal and urinary disorders	4/7
White blood cell decreasedInvestigations	4/7

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Ramucirumab + Nab-paclitaxel
Median	63 (54.9 to 77.3)

Sex: Female, Male
Sex: Female, Male(Participants)	Ramucirumab + Nab-paclitaxel
Female	4
Male	3

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Ramucirumab + Nab-paclitaxel
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	7
More than one race	0
Unknown or Not Reported	0

Stage of Disease
Stage of Disease(Participants)	Ramucirumab + Nab-paclitaxel
Stage IV	5
Stage IV B	2

ECOG Performance Status
ECOG Performance Status(Participants)	Ramucirumab + Nab-paclitaxel
Grade 1	6
Grade 2	1

Study locations

1 site

UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232, United States

References and documents

Study documents

Protocol and statistical analysis plan · Jul 9, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 19, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02730247
Lead sponsor: Liza Villaruz, MD
Responsible party: Liza Villaruz, MD (Assistant Professor of Medicine, Division of Hematology Oncology, University of Pittsburgh) — Sponsor-investigator
First posted: Apr 6, 2016
Start date: Jul 5, 2017
Primary completion: Sep 8, 2019
Completion: Sep 8, 2019
Results posted: Nov 19, 2020
Last update: Nov 19, 2020

Study contacts

Liza Villaruz, MD

principal investigator · University of Pittsburgh Cancer Institute, Department of Hematology Oncology

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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