Pembrolizumab in Refractory Advanced Esophageal Cancer

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02971956
Collaborator
Merck Sharp & Dohme LLC (Industry)
49
3
1
88.4
16.3
0.2

Study Details

Study Description

Brief Summary

This research study is studying a targeted therapy as a possible treatment for advanced esophageal cancer.

The study intervention involved in this study is:

-Pembrolizumab

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab for the participant specific disease but it has been approved for other uses.

Pembrolizumab, also known as KEYTRUDA or MK-3475, is approved in the USA and several other countries to treat other types of diseases.

The goal of this research study is to

-Evaluate the safety and efficacy of pembrolizumab in participants with advanced esophageal cancer that have not responded to standard treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
49 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Pembrolizumab in Refractory Advanced Esophageal Cancer
Actual Study Start Date :
Jan 18, 2017
Actual Primary Completion Date :
Jul 23, 2019
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pembrolizumab

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.

Drug: Pembrolizumab
Immune checkpoint inhibitor
Other Names:
  • Keytruda
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [Disease was evaluated each cycle on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 2.1 months with a maximum of 14.9 months.]

      The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

    Secondary Outcome Measures

    1. Median Progression-free Survival (PFS) [Disease was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 28.9 months]

      Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

    2. Median Overall Survival (OS) [Disease was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months.]

      OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

    3. Number of Patients Experiencing Grade 3-4 Treatment-Related Toxicity [Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months.]

      All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Outcome defined as the number of patients experiencing at least one treatment-related grade 3-4 AE of any type during the time of observation.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically confirmed, measurable, unresectable adenocarcinoma or squamous cell carcinoma of the esophagus. For the purposes of this study, undifferentiated carcinomas or adenosquamous carcinomas will be categorized as adenocarcinomas.

    • The primary tumor must originate in the esophagus. Tumors that involve the GE junction must meet Sievert Type 1 criteria: "Adenocarcinoma of the distal oesophagus which usually arises from an area with specialized intestinal metaplasia of the oesophagus (i.e. Barrett's oesophagus) and which may infiltrate the oesophagogastric junction from above." For the purposes of this protocol, this will be interpreted as: greater than 50% of the tumor must be above the GE junction or, alternatively, the tumor must involve the GE junction and arise in the setting of biopsy-documented Barrett's esophagus (specialized intestinal metaplasia).

    • Patients must have received at least one prior therapy for unresectable disease. Patients with recurrence within 6 months of completion of neoadjuvant or adjuvant therapy may be considered as having received one prior therapy for unresectable disease.

    • Be willing and able to provide written informed consent/assent for the trial.

    • Be ≥ 18 years of age on day of signing informed consent.

    • Have measurable disease based on irRECIST.

    • Be willing to provide tissue from a newly obtained biopsy of a tumor lesion, most commonly an EGD biopsy from the esophagus. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor. Please note, patients may not initiate therapy until the biopsy specimen is received at the Dana-Farber Cancer Institute.

    • The first 15 patients with adenocarcinoma will be offered an optional tumor biopsy (typically EGD biopsy) at 8 weeks. Starting with adenocarcinoma patient #16, patients must have an accessible tumor and must agree to tumor biopsy at 8 weeks; this will continue to be mandatory until a total of 20 patients have undergone biopsy at 8 weeks.

    • Have a performance status of 0 or 1 on the ECOG Performance Scale (Appendix A).

    • Female subject of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

    • Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 6.3.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.

    • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

    • Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of treatment initiation.

    Hematological

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

    • Platelets ≥80,000 / mcL

    • Hemoglobin ≥8.5 g/dL or ≥5.6 mmol/L

    -Renal

    • Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured creatinine clearance ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCL) Creatinine clearance should be calculated per institutional standard.

    -Hepatic

    • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN

    • AST (SGOT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

    • ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases

    • Albumin > 2.8 mg/dL

    -Coagulation

    • International Normalized Ratio (INR) OR Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

    • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

    Exclusion Criteria:
    • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Subjects requiring systemic steroids are excluded from the trial. The use of physiologic doses of corticosteroids may be approved after discussion with the sponsor.

    • Has a known history of active TB (Bacillus Tuberculosis)

    • Hypersensitivity to pembrolizumab or any of its excipients.

    • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

    • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    • Note: Subjects with ≤ Grade 2 neuropathy and alopecia are an exception to this criterion and may qualify for the study.

    • Note: If subject received major surgery, they must wait ≥ 3 weeks prior to starting study treatment. They must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

    • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.

    • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.

    • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

    • Has an active infection requiring systemic therapy.

    • Patients that require supplemental oxygen are excluded.

    • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

    • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

    • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

    • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

    • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

    • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

    • Has received a live vaccine within 30 days of planned start of study therapy.

    --Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

    • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Massachusetts General Hospital Boston Massachusetts United States 02114
    2 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02115
    3 Dana Farber Cancer Institute Boston Massachusetts United States 02115

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • Merck Sharp & Dohme LLC

    Investigators

    • Principal Investigator: Peter C. Enzinger, MD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Peter C. Enzinger, MD, Peter C. Enzinger MD, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02971956
    Other Study ID Numbers:
    • 16-293
    First Posted:
    Nov 23, 2016
    Last Update Posted:
    Apr 8, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Peter C. Enzinger, MD, Peter C. Enzinger MD, Dana-Farber Cancer Institute
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details from January 2017 to October 2018
    Pre-assignment Detail
    Arm/Group Title Pembrolizumab
    Arm/Group Description Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
    Period Title: Overall Study
    STARTED 49
    COMPLETED 49
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Pembrolizumab
    Arm/Group Description Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
    Overall Participants 49
    Age, Customized (years) [Median (Full Range) ]
    Median (Full Range) [years]
    64
    Sex: Female, Male (Count of Participants)
    Female
    39
    79.6%
    Male
    10
    20.4%
    Race/Ethnicity, Customized (Count of Participants)
    White
    44
    89.8%
    Black or African American
    2
    4.1%
    Asian
    1
    2%
    Other
    1
    2%
    More than one race
    1
    2%
    Region of Enrollment (participants) [Number]
    United States
    49
    100%

    Outcome Measures

    1. Primary Outcome
    Title Overall Response Rate (ORR)
    Description The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
    Time Frame Disease was evaluated each cycle on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 2.1 months with a maximum of 14.9 months.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pembrolizumab
    Arm/Group Description Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
    Measure Participants 49
    Number (95% Confidence Interval) [proportion of participant]
    0.08
    2. Secondary Outcome
    Title Median Progression-free Survival (PFS)
    Description Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
    Time Frame Disease was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 28.9 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pembrolizumab
    Arm/Group Description Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
    Measure Participants 49
    Median (95% Confidence Interval) [months]
    1.8
    3. Secondary Outcome
    Title Median Overall Survival (OS)
    Description OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
    Time Frame Disease was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pembrolizumab
    Arm/Group Description Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
    Measure Participants 49
    Median (95% Confidence Interval) [months]
    5.8
    4. Secondary Outcome
    Title Number of Patients Experiencing Grade 3-4 Treatment-Related Toxicity
    Description All grade 3-4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Outcome defined as the number of patients experiencing at least one treatment-related grade 3-4 AE of any type during the time of observation.
    Time Frame Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Pembrolizumab
    Arm/Group Description Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
    Measure Participants 49
    Count of Participants [Participants]
    6
    12.2%

    Adverse Events

    Time Frame Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 2.1 months with maximum of 14.9 months. All-Cause Mortality was evaluated each cycle on treatment and in long-term follow-up every 12 weeks for up to 5 years. Maximum follow-up in this study cohort was 38.7 months.
    Adverse Event Reporting Description Serious adverse events (AEs) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Maximum grade toxicity by type for a patient over time was calculated. No further data is available to specify classification of other beyond the general term.
    Arm/Group Title Pembrolizumab
    Arm/Group Description Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
    All Cause Mortality
    Pembrolizumab
    Affected / at Risk (%) # Events
    Total 49/49 (100%)
    Serious Adverse Events
    Pembrolizumab
    Affected / at Risk (%) # Events
    Total 6/49 (12.2%)
    Cardiac disorders
    Cardiac arrest 1/49 (2%)
    Eye disorders
    Eye disorders - Other 1/49 (2%)
    Gastrointestinal disorders
    Duodenal hemorrhage 1/49 (2%)
    Dysphagia 1/49 (2%)
    General disorders
    Pain 1/49 (2%)
    Investigations
    Aspartate aminotransferase increased 1/49 (2%)
    Metabolism and nutrition disorders
    Anorexia 1/49 (2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/49 (2%)
    Myalgia 1/49 (2%)
    Nervous system disorders
    Nervous system disorders - Other 1/49 (2%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/49 (2%)
    Hypoxia 1/49 (2%)
    Pneumonitis 2/49 (4.1%)
    Respiratory failure 1/49 (2%)
    Other (Not Including Serious) Adverse Events
    Pembrolizumab
    Affected / at Risk (%) # Events
    Total 46/49 (93.9%)
    Blood and lymphatic system disorders
    Anemia 32/49 (65.3%)
    Blood and lymphatic system disorders - Other 1/49 (2%)
    Cardiac disorders
    Atrial fibrillation 2/49 (4.1%)
    Chest pain - cardiac 2/49 (4.1%)
    Palpitations 1/49 (2%)
    Sinus tachycardia 8/49 (16.3%)
    Endocrine disorders
    Endocrine disorders - Other 1/49 (2%)
    Hyperthyroidism 1/49 (2%)
    Hypothyroidism 3/49 (6.1%)
    Eye disorders
    Eye disorders - Other 2/49 (4.1%)
    Vitreous hemorrhage 1/49 (2%)
    Gastrointestinal disorders
    Abdominal distension 2/49 (4.1%)
    Abdominal pain 15/49 (30.6%)
    Ascites 1/49 (2%)
    Constipation 17/49 (34.7%)
    Diarrhea 14/49 (28.6%)
    Dry mouth 3/49 (6.1%)
    Duodenal hemorrhage 1/49 (2%)
    Dyspepsia 4/49 (8.2%)
    Dysphagia 18/49 (36.7%)
    Esophageal hemorrhage 2/49 (4.1%)
    Esophageal pain 1/49 (2%)
    Esophageal perforation 1/49 (2%)
    Fecal incontinence 1/49 (2%)
    Gastric hemorrhage 1/49 (2%)
    Gastritis 1/49 (2%)
    Gastrointestinal disorders - Other 3/49 (6.1%)
    Gastrointestinal pain 1/49 (2%)
    Mucositis oral 2/49 (4.1%)
    Nausea 20/49 (40.8%)
    Obstruction gastric 1/49 (2%)
    Pancreatitis 1/49 (2%)
    Vomiting 12/49 (24.5%)
    General disorders
    Death NOS 3/49 (6.1%)
    Edema limbs 7/49 (14.3%)
    Fatigue 40/49 (81.6%)
    Fever 3/49 (6.1%)
    Gait disturbance 1/49 (2%)
    General disorders and administration site conditions - Other 3/49 (6.1%)
    Localized edema 1/49 (2%)
    Non-cardiac chest pain 4/49 (8.2%)
    Pain 7/49 (14.3%)
    Infections and infestations
    Abdominal infection 1/49 (2%)
    Bronchial infection 1/49 (2%)
    Lung infection 1/49 (2%)
    Investigations
    Activated partial thromboplastin time prolonged 1/49 (2%)
    Alanine aminotransferase increased 8/49 (16.3%)
    Alkaline phosphatase increased 26/49 (53.1%)
    Aspartate aminotransferase increased 20/49 (40.8%)
    Blood bilirubin increased 7/49 (14.3%)
    Creatinine increased 3/49 (6.1%)
    Investigations - Other 2/49 (4.1%)
    Lipase increased 1/49 (2%)
    Lymphocyte count decreased 3/49 (6.1%)
    Neutrophil count decreased 5/49 (10.2%)
    Platelet count decreased 12/49 (24.5%)
    Weight gain 1/49 (2%)
    Weight loss 10/49 (20.4%)
    White blood cell decreased 4/49 (8.2%)
    Metabolism and nutrition disorders
    Acidosis 1/49 (2%)
    Anorexia 21/49 (42.9%)
    Dehydration 8/49 (16.3%)
    Hypercalcemia 1/49 (2%)
    Hyperglycemia 31/49 (63.3%)
    Hyperkalemia 3/49 (6.1%)
    Hypernatremia 1/49 (2%)
    Hypoalbuminemia 31/49 (63.3%)
    Hypocalcemia 3/49 (6.1%)
    Hypokalemia 7/49 (14.3%)
    Hypomagnesemia 2/49 (4.1%)
    Hyponatremia 24/49 (49%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 4/49 (8.2%)
    Arthritis 1/49 (2%)
    Back pain 16/49 (32.7%)
    Bone pain 3/49 (6.1%)
    Chest wall pain 1/49 (2%)
    Generalized muscle weakness 8/49 (16.3%)
    Muscle weakness left-sided 1/49 (2%)
    Musculoskeletal and connective tissue disorder - Other 3/49 (6.1%)
    Myalgia 2/49 (4.1%)
    Neck pain 1/49 (2%)
    Pain in extremity 6/49 (12.2%)
    Nervous system disorders
    Ataxia 1/49 (2%)
    Dizziness 8/49 (16.3%)
    Dysgeusia 3/49 (6.1%)
    Headache 2/49 (4.1%)
    Memory impairment 2/49 (4.1%)
    Nervous system disorders - Other 5/49 (10.2%)
    Peripheral motor neuropathy 1/49 (2%)
    Peripheral sensory neuropathy 10/49 (20.4%)
    Syncope 1/49 (2%)
    Tremor 1/49 (2%)
    Psychiatric disorders
    Anxiety 4/49 (8.2%)
    Confusion 7/49 (14.3%)
    Depression 3/49 (6.1%)
    Insomnia 6/49 (12.2%)
    Renal and urinary disorders
    Hematuria 1/49 (2%)
    Proteinuria 2/49 (4.1%)
    Renal and urinary disorders - Other 1/49 (2%)
    Respiratory, thoracic and mediastinal disorders
    Cough 21/49 (42.9%)
    Dyspnea 17/49 (34.7%)
    Epistaxis 3/49 (6.1%)
    Hypoxia 1/49 (2%)
    Pleural effusion 2/49 (4.1%)
    Pneumonitis 1/49 (2%)
    Respiratory, thoracic and mediastinal disorders - Other 3/49 (6.1%)
    Tracheal fistula 4/49 (8.2%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/49 (2%)
    Dry skin 1/49 (2%)
    Hyperhidrosis 4/49 (8.2%)
    Pruritus 5/49 (10.2%)
    Rash acneiform 2/49 (4.1%)
    Rash maculo-papular 7/49 (14.3%)
    Skin and subcutaneous tissue disorders - Other 4/49 (8.2%)
    Vascular disorders
    Hypertension 29/49 (59.2%)
    Hypotension 2/49 (4.1%)
    Thromboembolic event 3/49 (6.1%)
    Vascular disorders - Other 1/49 (2%)

    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 Peter C. Enzinger MD
    Organization Dana-Farber Cancer Institute
    Phone (877) 442-3324
    Email Peter_Enzinger@dfci.harvard.edu
    Responsible Party:
    Peter C. Enzinger, MD, Peter C. Enzinger MD, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT02971956
    Other Study ID Numbers:
    • 16-293
    First Posted:
    Nov 23, 2016
    Last Update Posted:
    Apr 8, 2022
    Last Verified:
    Apr 1, 2022