CompletedNCT01191697Updated Nov 3, 2025Results posted

CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer

A Phase 2 interventional study of bevacizumab and trastuzumab in Esophageal Cancer and Gastric Cancer, sponsored by Dana-Farber Cancer Institute. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-03.

Sponsored by Dana-Farber Cancer Institute · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 37
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

The purpose of this study is to determine the safety and effectiveness of a combination of chemotherapy, capecitabine and oxaliplatin, plus the antibodies bevacizumab and trastuzumab. Trastuzumab (also called Herceptin) is an antibody that attacks HER2 protein in tumor cells. Bevacizumab (also called Avastin) works by slowing or stopping the growth of cells in cancer tumors by decreasing the blood supply of the tumors. If blood supply is decreased, oxygen and nutrients that are needed for tumor growth are decreased. The chemotherapy used in this trial is called CAPOX, which is an abbreviation of capecitabine and oxaliplatin.

Read the detailed description

We recommend that the participants have a vascular access device, more commonly known as a PORT, inserted prior to starting chemotherapy. A port is a small device that is inserted under the skin (usually near the collar bone) by a minor surgical procedure and is then connected to one of the large veins inside the chest. The port will be used to give the intravenous medications.
During the first cycle, the participant will receive trastuzumab intravenously on Day 1. Cycle 2 will then start one week later. On this day, bevacizumab will be given intravenously first followed by trastuzumab and then oxaliplatin. The participant will then start taking capecitabine tablets orally twice a day for 14 days. Each treatment cycle is 21 days long.
Participants will have the following tests and procedures at specific time points during study treatment; physical exam, blood tests, CT scan, MUGA scan or echocardiogram, and urine test.

Conditions studied

Esophageal Cancer
Gastric Cancer

Browse trials for

Keywords

HER2 positive

In context

Esophageal Neoplasms

1,593 studies on the registry are indexed under Esophageal Neoplasms; 461 are open to participants now.

This study's enrollment of 37 is below the median of 58 across 1,171 interventional studies indexed under Esophageal Neoplasms.

Browse Esophageal Neoplasms studies →

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

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

Confirmed HER2-positive esophageal, GE junction or gastric adenocarcinoma that is metastatic or unresectable.
All patients must have available tumor sample (either paraffin block or 15 freshly cut, unstained slides) prior to study entry.

Part II: Patient must have primary esophagogastric tumor in place or other tumor that is accessible for mandatory biopsy.

Measurable disease, defined in RECIST 1.1
18 years of age or older
Life expectancy of greater than 12 weeks
ECOG performance status of 0 or 1
Organ and marrow function as outlined in the protocol
Women of child-bearing potential and men must agree to use adequate contraception during study participation and for 30 days from the date of the last study drug administration.
Part II only: Participant agrees to undergo mandatory pre and post loading dose of trastuzumab biopsy for correlative science.

Exclusion criteria

Exclusion Criteria:

Prior therapy with any of the following; capecitabine, oxaliplatin, bevacizumab or trastuzumab is not allowed. May have received and completed adjuvant therapy at least 6 months prior to study entry or one prior therapy for metastatic disease as long as it did not include any of the above agents.
Chemotherapy or radiotherapy to greater then 25% of bone marrow within 4 weeks prior to entering the study.
Palliative radiation therapy to isolated bone metastasis within 2 weeks of initiating therapy.
Major surgery, open biopsy, significant traumatic injury within 4 weeks prior to study entry,.
Minor surgery, including placement of vascular access device within 7 days prior to the first dose of bevacizumab.
Residual toxicity from prior chemotherapy and/or radiation therapy of Grade 2 or greater.
Participants may not be receiving any concurrent investigational agents
Active brain or other CNS metastasis by history or clinical examination.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine, bevacizumab or trastuzumab. No known allergy or hypersensitivity to Chinese hamster ovary, or any of the study agents. No known DPD deficiency.
Warfarin is prohibited; anticoagulation using low molecular weight heparin is allowed.
Uncontrolled, intercurrent illness
Patients with a history of other malignancy are not eligible except for the following circumstances: disease-free for at least 3 years and are deemed to be at low risk for recurrence of that malignancy; cervical cancer in situ, basal cell or squamous cell carcinoma of the skin that was treated with curative intent within the past 5 years.
Known HIV seropositivity, hepatitis C, acute or chronic hepatitis B or other serious active infection
LVEF less than 50% as determined by MUGA scan or echocardiogram within 28 days prior to initiation of therapy
Inadequately controlled hypertension
History of prior hypertensive crisis or hypertensive encephalopathy
History of any arterial thrombosis, CVA, TIA, MI or unstable angina in past 6 months.
Evidence of bleeding diathesis or coagulopathy
Serious, unhealed wounds, bone fractures or skin ulcers
Pregnant or breast feeding
Greater than grade 1 peripheral neuropathy at baseline
Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 37 participants (actual)

Study arms

Experimental
Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine for patients with HER2-positive metastatic esophagogastric cancer. Each cycle is 21 days. Cycle 1, Day 1 Trastuzumab (loading dose) 4mg/kg IV Cycle 2, Day 1 and all Subsequent Cycles Bevacizumab (7.5mg/kg) IV Trastuzumab (6mg/kg) IV Oxaliplatin (130mg/m2) IV Capecitabine (1200mg/m2) PO (taken Days 1-14 of each cycle) Patients remained on treatment until disease progression, intercurrent illness that prevented further administration of treatment, unacceptable adverse events, participant decision to withdraw consent or general or specific changes in the participant's condition that rendered the participant unacceptable for further treatment.
Drug: bevacizumab · Drug: trastuzumab · Drug: oxaliplatin · Drug: capecitabine

Interventions

Drugbevacizumab
Given intravenously on day 1 of each cycle beginning cycle 2
Also known as: Avastin
Drugtrastuzumab
Given intravenously on day 1 of each treatment cycle
Also known as: Herceptin
Drugoxaliplatin
Given intravenously on day one of each cycle beginning cycle 2
Drugcapecitabine
Taken orally on days 1-14 of each cycle beginning cycle 2
Also known as: xeloda

What researchers measure

Primary outcomes

Objective Response Rate (ORR)
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. 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: Patients received a median of 19 cycles of therapy (Interquartile range (IQR): 8 - 34.5 cycles). Median duration of follow-up of 23.2 months (IQR: 11.0 - 46.9 months ).

Secondary outcomes

Median Overall Survival
Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.
Time frame: 23.2 months (IQR: 11.0 - 46.9 months ).
Median Duration of Response (DOR)
DOR is defined as the time from date of first documented confirmed objective response to date of first documented progressive disease (PD). Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time frame: 23.2 months (IQR: 11.0 - 46.9 months ).
Median Progression Free Survival (PFS)
PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time frame: Patients received a median of 19 cycles of therapy (Interquartile range (IQR): 8 - 34.5 cycles). Median duration of follow up of 23.2 months (IQR: 11.0 - 46.9 months ).

Results

Posted Sep 5, 2023

Participant flow

Of 61 participants assessed for eligibility, 37 met the inclusion criteria and enrolled for treatment. One patient withdrew consent prior to starting therapy. 36 were evaluable for efficacy and safety.

Participant flow — Overall Study
Milestone	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Started	37
Analyzed popopulation	36
Completed	0
Not completed	37
Withdrew: Death	1
Withdrew: Physician decision	2
Withdrew: Pursue chemoradiation	2
Withdrew: Break from chemotherapy	2
Withdrew: Withdrawal by subject	1
Withdrew: Surveillance	1
Withdrew: Adverse event	2
Withdrew: Subject never received treatment and wasn't analyzed.	1
Withdrew: Not completed but analyzed	25

Outcome measures

PrimaryObjective Response Rate (ORR)

ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. 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:: Patients received a median of 19 cycles of therapy (Interquartile range (IQR): 8 - 34.5 cycles). Median duration of follow-up of 23.2 months (IQR: 11.0 - 46.9 months ).
Reported as:: Number · percentage of patients

Objective Response Rate (ORR)
percentage of patients	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Objective Response Rate (ORR)	81

SecondaryMedian Overall Survival

Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.

Time frame:: 23.2 months (IQR: 11.0 - 46.9 months ).
Reported as:: Median · months

Median Overall Survival
months	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Median Overall Survival	23.2 (16.6 to 36.4)

SecondaryMedian Duration of Response (DOR)

DOR is defined as the time from date of first documented confirmed objective response to date of first documented progressive disease (PD). Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

Time frame:: 23.2 months (IQR: 11.0 - 46.9 months ).
Reported as:: Median · months

Median Duration of Response (DOR)
months	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Median Duration of Response (DOR)	14.9 (2.4 to 95.9)

SecondaryMedian Progression Free Survival (PFS)

PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation or start of new anticancer therapy. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.

Time frame:: Patients received a median of 19 cycles of therapy (Interquartile range (IQR): 8 - 34.5 cycles). Median duration of follow up of 23.2 months (IQR: 11.0 - 46.9 months ).
Reported as:: Median · months

Median Progression Free Survival (PFS)
months	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Median Progression Free Survival (PFS)	14.0 (11.3 to 36.4)

Adverse events

Collected over All adverse events experienced by participants will be collected from the time of the first dose of study treatment, throughout the study, and until the final study visit. Participants continuing to experience toxicity at the off-study visit may be contacted for additional assessments until the toxicity has resolved or is deemed irreversible. (10 years and 7 months). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine	31/36 (86.1%)	13/36 (36.1%)	36/36 (100%)

Most frequent serious events

Showing 10 of 17

Most frequent serious events
Event	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
DehydrationMetabolism and nutrition disorders	5/36
PneumothoraxRespiratory, thoracic and mediastinal disorders	3/36
Abdominal PainGastrointestinal disorders	2/36
Pulmonary EmbolismBlood and lymphatic system disorders	1/36
PneumoniaRespiratory, thoracic and mediastinal disorders	1/36
HponatremiaBlood and lymphatic system disorders	1/36
Pneumatosis intestinalisGastrointestinal disorders	1/36
HypertriglyceridemiaBlood and lymphatic system disorders	1/36
Perforated GallbladderGastrointestinal disorders	1/36
HerniaGeneral disorders	1/36

Most frequent other events

Showing 10 of 106

Most frequent other events
Event	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Peripheral sensory neuropathyNervous system disorders	32/36
DiarrheaGastrointestinal disorders	29/36
NauseaGastrointestinal disorders	27/36
AnemiaBlood and lymphatic system disorders	26/36
Platelet count decreasedInvestigations	21/36
Aspartate aminotransferase increasedInvestigations	19/36
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders	18/36
FatigueGeneral disorders and administration site conditions	16/36
DysesthesiaNervous system disorders	15/36
HypertensionVascular disorders	15/36

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Median	55.5 (32 to 79)

Sex: Female, Male
Sex: Female, Male(Participants)	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Female	4
Male	32

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
Hispanic or Latino	1
Not Hispanic or Latino	34
Unknown or Not Reported	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	34
More than one race	0
Unknown or Not Reported	0

Region of Enrollment
Region of Enrollment(participants)	Trastuzumab, Bevacizumab, Oxaliplatin and Capecitabine
United States	36

Study locations

2 sites

Massachusetts General Hospital
Boston, Massachusetts 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02115, United States

References and documents

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Study documents

Protocol and statistical analysis plan · Mar 18, 2019

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

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 3, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01191697
Lead sponsor: Dana-Farber Cancer Institute
Collaborators: Brigham and Women's Hospital, Massachusetts General Hospital, Genentech, Inc.
Responsible party: Peter Enzinger, MD (Principal Investigator, Dana-Farber Cancer Institute) — Principal investigator
First posted: Aug 31, 2010
Start date: Feb 2011
Primary completion: Dec 2021
Completion: Aug 2024
Results posted: Sep 5, 2023
Last update: Nov 3, 2025

Study contacts

Peter Enzinger, MD

principal investigator · Dana-Farber Cancer Institute

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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