Study of Nab-Paclitaxel and Ramucirumab as Second-line Treatment for Patients With Metastatic Gastroesophageal Cancer

Phase II Study of Nab-Paclitaxel and Ramucirumab for the Second-line Treatment of Patients With Metastatic Gastroesophageal Cancer

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02317991

Enrollment

Registered

2014-12-17

Start date

2015-05-05

Completion date

2021-05-21

Last updated

2022-07-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastroesophageal Cancer

Keywords

gastroesophageal adenocarcinoma, nab-paclitaxel, Abraxane, ramucirumab, Cyramza, GE junction

Brief summary

The purpose of this study is to determine whether nab-Paclitaxel (Abraxane®) and ramucirumab (Cyramza®) are effective when used in combination for treating patients with metastatic gastroesophageal cancer who have either progressed or not responded to prior therapy.

Detailed description

Adenocarcinoma of the esophagus and the gastroesophageal junction (GE junction) is the ninth most common cancer worldwide. Ramucirumab (Cyramza®), a monoclonal antibody, is approved as a single agent and in combination with paclitaxel as a treatment for patients with metastatic gastric or GE junction adenocarcinoma whose cancer has progressed after prior chemotherapy. Nab-paclitaxel (Abraxane®) is an albumin-based formulation of paclitaxel which was developed to improve the therapeutic index and reduce toxicity. Nab-paclitaxel is approved in over 40 countries/regions for treatment of various metastatic cancers including breast cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer. In this Phase II study, the investigators propose to combine the less toxic nab-paclitaxel to increase tumor uptake of the drug and improve efficacy while minimizing side effects. The biological rationale of using this combination is that ramucirumab will inhibit tumor angiogenesis and nab-paclitaxel will induce apoptosis of the rapidly dividing tumor cell.

Interventions

DRUGnab-paclitaxel

nab-paclitaxel 125 mg/m\^2 IV

BIOLOGICALramucirumab

Ramucirumab 8 mg/kg IV

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Patients with histologically confirmed metastatic adenocarcinoma of the esophagus, GE junction, or stomach who progressed on one prior line of chemotherapy in the metastatic setting. 2. Measurable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 4. Adequate hematologic, renal, and hepatic functions 5. Patients must have \< Grade 2 pre-existing peripheral neuropathy (per National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v 4.03) 6. Life expectancy \> 3 months

Exclusion criteria

1. Patients who have received any other investigational agents, chemotherapy, biologic therapy, or radiation therapy within the 28 days prior to Day 1 of the study. For investigational, chemotherapy, or biologic therapy, patients will be allowed on study if five half-lives or greater have elapsed since last dose of drug or 28 days, whichever is shorter. 2. Patients with prior taxane chemotherapy or agents which act by primary anti-angiogenic mechanisms. 3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results. 4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study initiation, or anticipation of need for major surgical procedure during the course of the study. 5. Evidence or history of uncontrolled hypertension, proteinuria, non-healing wound, ulcer, bone fracture, hemoptysis, valvular disease, abdominal fistula, GI perforation, intra-abdominal abscess, bleeding diathesis or coagulopathy that would exclude patients from treatment with anti-angiogenesis agents. 6. Therapeutic anticoagulation with coumarin-derivatives will not be permitted. However, a maximum daily dose of 1 mg will be permitted for port line patency. Anticoagulation with low molecular weight heparin or anti-Factor Xa agents will be allowed. 7. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise safety of treatment as so judged by treating physician (i.e., severely impaired lung function, severe infection, ventricular arrhythmias active ischemic heart disease, known active vasculitis of any cause, chronic liver or renal disease).

Design outcomes

Primary

Measure	Time frame	Description
Progression-Free Survival (PFS)	up to 1 year	Measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation in Solid Tumors Criteria (RECIST v1.1), or death on study from any cause. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Participants who are alive and free from disease progression were censored at the date of the last adequate tumor assessment. If no adequate post-treatment tumor assessments were obtained for participants, PFS will be censored on Day 1.

Secondary

Measure	Time frame	Description
Overall Response Rate (ORR)	every 8 weeks up to 1 year	ORR is defined as the percentage of patients with confirmed complete response (CR) or confirmed partial response (PR), i.e., two CRs and/or PRs at least 4 weeks apart, according to the RECIST v1.1 criteria. CR=disappearance of all target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time to Progression (TTP)	up to 1 year	TTP is defined as the time from the first day of study drug administration (Day 1) to objective disease progression as defined by the RECIST v1.1 criteria. Patients who are alive and free from disease progression will be censored at the date of the last adequate tumor assessment. If no adequate post-treatment tumor assessments were obtained for a patient, TTP will be censored on Day 1. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions.
Overall Survival (OS)	up to 1 year	OS is defined as the time from the first treatment until date of death due to any cause. In the absence of confirmation of death or lack of data beyond follow-up period, the survival time was censored to last date the participant was known to be alive.

Other

Measure	Time frame	Description
Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability	For duration of treatment, up to of 6 months	Adverse events will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03

Countries

United States

Participant flow

Participants by arm

Arm	Count
Nab-paclitaxel and Ramucirumab All patients will receive 125 mg/m\^2 of nab-Paclitaxel intravenously (IV) on Days 1, 8, and 15 of a 28-day cycle (weekly for 3 weeks, with 1 week of rest). Patients will receive ramucirumab 8mg/kg IV in combination with nab-paclitaxel on Days 1 and 15 of the 28-day cycle. nab-paclitaxel: nab-paclitaxel 125 mg/m\^2 IV ramucirumab: Ramucirumab 8 mg/kg IV	65
Total	65

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	12
Overall Study	Death	4
Overall Study	Progressive Disease	41
Overall Study	Withdrawal by Subject	8

Baseline characteristics

Characteristic	Nab-paclitaxel and Ramucirumab
Age, Continuous	63 years
Participants with HER2 positive status (confirmed by FISH)	12 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	6 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	58 Participants
Region of Enrollment United States	65 Participants
Sex: Female, Male Female	16 Participants
Sex: Female, Male Male	49 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	51 / 65
other Total, other adverse events	62 / 65
serious Total, serious adverse events	30 / 65

Outcome results

Primary

Progression-Free Survival (PFS)

Measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation in Solid Tumors Criteria (RECIST v1.1), or death on study from any cause. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Participants who are alive and free from disease progression were censored at the date of the last adequate tumor assessment. If no adequate post-treatment tumor assessments were obtained for participants, PFS will be censored on Day 1.

Time frame: up to 1 year