Nintedanib in Patients With Advanced Esophagogastric Cancer

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT02234596
Collaborator
(none)
34
6
1
67.6
5.7
0.1

Study Details

Study Description

Brief Summary

This is a phase II study of Nintedanib in patients with metastatic or recurrent esophagogastric cancer. The goal of the study is to evaluate the efficacy of Nintedanib, an orally available triple kinase inhibitor targeting the receptors of the vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) receptor pathways.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
34 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Trial of Nintedanib in Patients With Advanced Esophagogastric Cancer
Actual Study Start Date :
Sep 4, 2014
Actual Primary Completion Date :
Apr 22, 2020
Actual Study Completion Date :
Apr 22, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nintedanib

Drug: Nintedanib
Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.

Outcome Measures

Primary Outcome Measures

  1. 6-month Progression-free Survival (PFS) [6 months]

Secondary Outcome Measures

  1. Objective Response Rate [3 years]

    defined as both complete response (CR) and partial response (PR), as measured by RECIST response criteria.

  2. Participants Evaluated for Toxicities [3 years]

    The severity of adverse event should be classified and recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Pathologically or cytologically MSKCC confirmed esophagogastric adenocarcinoma.

  • Metastatic diseases measurable or evaluable on a CT or MRI scan according to RECIST 1.1 criteria. Locally recurrent disease that is not amenable to potentially curative surgery or radiation therapy is also allowed. Lesions must be ≥10mm in size. Recurrent or metastatic disease within a prior radiation field is acceptable as long as the disease has progressed in the radiation field by RECIST criteria.

  • Patients are allowed to have had a maximum of 1 prior chemotherapy regimen for metastatic disease. Patients are allowed to have a maximum of two prior regimens if they previously received neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for their initial localized disease.

  • Patients aged 18 years or older.

  • Life expectancy of at least 6 months.

  • Karnofsky Performance Status (KPS) performance score ≥ 70%.

  • Patients must be able to reliably take and swallow oral medications.

  • Patients with prior deep vein thrombosis (DVT) or pulmonary embolism (PE) currently on anticoagulation regimen will be permitted.

  • Adequate bone marrow, liver, and renal function as assessed by the following:

  • Hemoglobin ≥ 9.0 g/dL.

  • Absolute neutrophil count (ANC) ≥ 1,500/mm3.

  • Platelet count ≥ 100,000/mm3.

  • Total bilirubin within normal limits, 0-1 mg/dL.

  • AST and ALT< 1.5 times ULN. (For patients with liver involvement: AST and ALT≤ 2.5 ULN).

  • International normalized ratio (INR) < 2, prothrombin time (PT) < 20 sec, and partial thromboplastin time (PTT) < 55 sec .

  • Creatinine < 1.5 x the ULN or GFR<45 ml/min.

Exclusion Criteria:
  • HER-2 positive esophagogastric cancer. Patients with unknown HER2 status are permitted.

  • Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating esophagogastric cancer. Last prior therapy must have been completed at least 2 weeks (14 days) prior to starting Nintedanib.

  • Concurrent radiotherapy is not permitted for disease progression on treatment on protocol. However, symptomatic treatment for pre-existing non-target lesions would be allowed with approval from the principal investigator.

  • Prior treatment with VEGFR inhibitor.

  • Brain metastases or leptomeningeal disease.

  • History of arterial thromboembolic (arterial blood clot) or hemorrhagic event with the exception of patients with pulmonary embolism stable on an anticoagulation regimen.

  • Patients with a cerebrovascular accident or transient ischemic attack within the past six months.

  • Patients on warfarin for any reason.

  • Patient with known pre-existing interstitial lung disease.

  • History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure, New York Heart Association (NYHA) functional classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 month prior to the study entry.

  • Patients with history of proteinuria grade ≥ 2.

  • Women of childbearing potential (WOCBP), or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial and for at least three months after the end of active therapy.

  • Women who are pregnant or breast-feeding. Persistence of clinically relevant therapy related toxicity from previous chemotherapy and/or radiotherapy. This does not include hemoglobin or other hematologic or laboratory criteria, as long as eligibility criteria are met

  • Other malignancies within the past 5 years other than non-melanoma superficial skin cancer or carcinoma in situ of the cervix.

  • Concurrent medical conditions or injury which may increase the risk of toxicity, including ongoing or active infection, history of significant bleeding disorder unrelated to cancer (congenital bleeding disorders, acquired bleeding disorders within one year), history of HIV-positive, or active or chronic hepatitis C and/or B infection.

  • Known or suspected active drug or alcohol abuse.

  • Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug. Patients who are unable to orally swallow the study medication.

  • Known hypersensitivity to trial drug.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Memoral Sloan Kettering Cancer Center Basking Ridge New Jersey United States
2 Memorial Sloan Kettering Monmouth Middletown New Jersey United States 07748
3 Memorial Sloan Kettering Cancer Center @ Suffolk Commack New York United States 11725
4 Memorial Sloan Kettering Westchester Harrison New York United States 10604
5 Memorial Sloan Kettering Cancer Center 1275 York Avenue New York New York United States 10065
6 Memorial Sloan Kettering at Mercy Medical Center Rockville Centre New York United States

Sponsors and Collaborators

  • Memorial Sloan Kettering Cancer Center

Investigators

  • Principal Investigator: Yelena Janjigian, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02234596
Other Study ID Numbers:
  • 14-094
First Posted:
Sep 9, 2014
Last Update Posted:
Jan 25, 2021
Last Verified:
Apr 1, 2020
Keywords provided by Memorial Sloan Kettering Cancer Center
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Nintedanib
Arm/Group Description Nintedanib: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.
Period Title: Overall Study
STARTED 34
COMPLETED 32
NOT COMPLETED 2

Baseline Characteristics

Arm/Group Title Nintedanib
Arm/Group Description Nintedanib: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.
Overall Participants 34
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]
60
Sex: Female, Male (Count of Participants)
Female
5
14.7%
Male
29
85.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
1
2.9%
Not Hispanic or Latino
7
20.6%
Unknown or Not Reported
26
76.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
Asian
3
8.8%
Native Hawaiian or Other Pacific Islander
0
0%
Black or African American
2
5.9%
White
28
82.4%
More than one race
0
0%
Unknown or Not Reported
1
2.9%
Region of Enrollment (Count of Participants)
United States
34
100%

Outcome Measures

1. Primary Outcome
Title 6-month Progression-free Survival (PFS)
Description
Time Frame 6 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Nintedanib
Arm/Group Description Nintedanib: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.
Measure Participants 32
Median (95% Confidence Interval) [months]
1.9
2. Secondary Outcome
Title Objective Response Rate
Description defined as both complete response (CR) and partial response (PR), as measured by RECIST response criteria.
Time Frame 3 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Nintedanib
Arm/Group Description Nintedanib: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.
Measure Participants 32
Complete Response
0
0%
Partial Response
0
0%
Stable Disease
14
41.2%
Progressive Disease
18
52.9%
3. Secondary Outcome
Title Participants Evaluated for Toxicities
Description The severity of adverse event should be classified and recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Time Frame 3 years

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Nintedanib
Arm/Group Description Nintedanib: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.
Measure Participants 32
Count of Participants [Participants]
32
94.1%

Adverse Events

Time Frame 3 years
Adverse Event Reporting Description
Arm/Group Title Nintedanib
Arm/Group Description Nintedanib: Nintedanib 200mg twice daily administered continuously. Patients will continue on treatment until progression of disease. Each cycle consists of 28 days continuously, unless interrupted for intolerable toxicity.
All Cause Mortality
Nintedanib
Affected / at Risk (%) # Events
Total 26/34 (76.5%)
Serious Adverse Events
Nintedanib
Affected / at Risk (%) # Events
Total 8/34 (23.5%)
Blood and lymphatic system disorders
Anemia 1/34 (2.9%)
Cardiac disorders
Heart Failure 1/34 (2.9%)
Gastrointestinal disorders
Abdominal pain 1/34 (2.9%)
Constipation 1/34 (2.9%)
Nausea 2/34 (5.9%)
Vomiting 1/34 (2.9%)
General disorders
Death NOS 3/34 (8.8%)
Fatigue 2/34 (5.9%)
Fever 1/34 (2.9%)
Infections and infestations
Skin infection 1/34 (2.9%)
Investigations
Blood bilirubin increased 1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Back pain 1/34 (2.9%)
Nervous system disorders
Dizziness 1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea 2/34 (5.9%)
Pleural effusion 1/34 (2.9%)
Skin and subcutaneous tissue disorders
Skin & subcutaneous tissue disorders, Other, spec 1/34 (2.9%)
Vascular disorders
Thromboembolic event 1/34 (2.9%)
Other (Not Including Serious) Adverse Events
Nintedanib
Affected / at Risk (%) # Events
Total 32/34 (94.1%)
Blood and lymphatic system disorders
Anemia 3/34 (8.8%)
Gastrointestinal disorders
Diarrhea 14/34 (41.2%)
Nausea 13/34 (38.2%)
Vomiting 4/34 (11.8%)
Abdominal pain 3/34 (8.8%)
Constipation 2/34 (5.9%)
Dyspepsia 2/34 (5.9%)
Mucositis oral 2/34 (5.9%)
General disorders
Fatigue 18/34 (52.9%)
Investigations
Aspartate aminotransferase increased 12/34 (35.3%)
Alanine aminotransferase increased 11/34 (32.4%)
Alkaline phosphatase increased 11/34 (32.4%)
Platelet count decreased 5/34 (14.7%)
White blood cell decreased 4/34 (11.8%)
Blood bilirubin increased 3/34 (8.8%)
Lymphocyte count decreased 2/34 (5.9%)
Metabolism and nutrition disorders
Anorexia 4/34 (11.8%)
Hyperglycemia 3/34 (8.8%)
Nervous system disorders
Peripheral sensory neuropathy 2/34 (5.9%)
Skin and subcutaneous tissue disorders
Dry skin 2/34 (5.9%)
Pruritus 2/34 (5.9%)
Vascular disorders
Hypertension 16/34 (47.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. Yelena Janjigian,
Organization Memorial Sloan Kettering Cancer Center
Phone 646-888-4186
Email janjigiy@mskcc.org
Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT02234596
Other Study ID Numbers:
  • 14-094
First Posted:
Sep 9, 2014
Last Update Posted:
Jan 25, 2021
Last Verified:
Apr 1, 2020