Study of Docetaxel, Cisplatin, and Fluorouracil (Modified DCF) With Bevacizumab in Patients With Unresectable or Metastatic Gastroesophageal Adenocarcinoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00390416
• Collaborator: Sanofi (Industry), Genentech, Inc. (Industry)
• Enrollment: 48
• Locations: 5
• Arm: 1
• Duration (Months): 63
• Patients Per Site: 9.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is being done to find out what effects a drug named/called bevacizumab has on patients and patients' tumors when given together with standard chemotherapy drugs. Making new blood vessels seems to be important for many tumors to grow. Bevacizumab is a new type of treatment for cancer that blocks the growth of new tumor blood vessels. In this study, the researchers will combine bevacizumab with chemotherapy drugs that are standard for the patient's disease and include cisplatin, docetaxel, fluorouracil, and leucovorin. The way the original combination of cisplatin, docetaxel, and fluorouracil was given caused many side effects including gastrointestinal symptoms, weakness, and a drop in the blood count of infection fighting cells. For this study, the researchers have modified this combination to give lower doses of the medicines more often, to reduce side effects from the chemotherapy. Patients will receive bevacizumab with this modified combination of docetaxel, cisplatin, and fluorouracil. This study is called a phase II study. In this study, everyone will have similar tumors and receive the same treatment.

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasms; Esophageal Neoplasms	Drug: Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Docetaxel, Cisplatin, and Fluorouracil (Modified DCF) With Bevacizumab in Patients With Unresectable or Metastatic Gastroesophageal Adenocarcinoma
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin	Drug: Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin; Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes

Outcome Measures

Primary Outcome Measures

1. 6 Month Progression Free Survival [6 months]

   as measured from the start of the treatment to the date of either documentation of disease progression or death. As we have previously, we will define progression of disease as per RECIST criteria. As per RECIST criteria, any evidence of progression in non-measurable lesions, measurable lesions, or the development of new lesions, would qualify as disease progression .RECIST criteria as defined by CTEP (http://ctep.info.nih.gov/Policies).

2. 1-year Survival [1 year]

Secondary Outcome Measures

1. Patients With Measurable Disease the Confirmed Response Rate [up to 2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed metastatic or unresectable gastric or esophageal adenocarcinoma, including GEJ adenocarcinoma which will be classified according to Siewert's classification type I, II, or III.

• Histological documentation of local recurrence or metastasis is strongly encouraged, unless the risk of such a procedure outweighs the potential benefit of confirming the metastatic disease.

• If no histologic confirmation, then the metastases or recurrence will require documentation by a 2nd radiographic procedure (i.e. positron emission tomography [PET] scan or magnetic resonance imaging [MRI] in addition to the computed tomography [CT] scan). If the imaging procedure does not confirm recurrent or metastatic disease, biopsy confirmation will be required.

• Patients must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease. Measurable disease is defined as that which can be measured in at least one dimension as > or = 20 mm with conventional techniques, or > or = 10 mm by high resolution imaging. Disease that is identified on radiology studies, but does not meet the criteria for measurable disease, is considered non-measurable - see section 12.1.1 of protocol for further details.

• No prior chemotherapy for metastatic or unresectable disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration. Patients may not have received prior docetaxel or cisplatin, or bevacizumab or any other novel biologic anti-angiogenic agent.

• Age 18 years or older.

• Karnofsky performance status > or = 70% (ECOG performance status 0-1).

• Peripheral neuropathy < or = grade 1

• Hematologic (minimal values):

• White blood cell count > or = 3000/mm3

• Absolute neutrophil count > or = 1500 cells/mm3

• Hemoglobin > or = 9.0 g/dl

• Platelet count > or = 100,000/mm3

• Hepatic (minimal values):

• Total bilirubin < or = to upper limit of normal (ULN)

• AST and ALT and alkaline phosphatase must be within the eligible range. In determining eligibility, the more abnormal of the two values (AST or ALT) should be used. AST and ALT and alkaline phosphatase should be no more than 1-1.5 times the upper limit of normal.

• Kidney function (minimal values):

• Serum creatinine < or = 1.5 mg/dl

• Urinalysis < 2+ proteinuria; urine protein (mg/dl)/urine creatinine (mg/dl) ratio (Up/c) < 1.0

• The patient has a PT (INR) < or = 1.5 and a PTT < or = 3 seconds above the upper limits of normal if the patient is not on anticoagulation therapy. If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:

1. The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin.

2. The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices).

• Women of childbearing potential must have a negative pregnancy test. Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.

• Ability to understand informed consent and signing of written informed consent document prior to initiation of protocol therapy.

Exclusion Criteria:

• Patients who have received previous chemotherapy for the treatment of metastatic or unresectable gastric, GEJ, or esophageal adenocarcinoma are ineligible. Patients who have received previous pre- or post-operative chemotherapy or chemoradiation are ineligible if therapy was completed less than 6 months prior to study registration. Patients must have recovered from adverse events from any previous therapy.

• Patients who have received previous bevacizumab, docetaxel, or cisplatin.

• Patients with a history of another neoplastic disease within the past three years, excluding basal cell carcinoma of the skin, cervical carcinoma in situ, or nonmetastatic prostate cancer.

• Patients with brain or central nervous system metastases, including leptomeningeal disease.

• Minor surgical procedure such as fine needle aspiration, core biopsy, laparoscopy, or mediport placement within 7 days prior to initiating treatment.

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0

• Anticipation of need for major surgical procedure during the course of the study.

• Pregnant (positive pregnancy test) or breast feeding.

• Urine protein:creatinine (Up/c) ratio > or = 1.0 at screening

• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to the initiation of treatment.

• Serious, non-healing wound, ulcer, or bone fracture.

• Blood pressure > 150/100 mmHg

• Significant cardiac disease defined as:

• Unstable angina

• New York Heart Association (NYHA) grade II or greater

• Congestive heart failure

• History of myocardial infarction within 6 months

• Evidence of bleeding diathesis or coagulopathy.

• History of a stroke or cerebrovascular accident (CVA) within 6 months.

• Clinically significant peripheral vascular disease.

• Clinically significant hearing loss or ringing in the ears.

• Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.

• Inability to comply with study and/or follow-up procedures.

• Patients with any other medical condition or reason, in the investigator's opinion, that makes the patient unstable to participate in a clinical trial.

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 Cancer Center @ Suffolk	Commack	New York	United States	11725
3	Memorial Sloan-Kettering Cancer Center 1275 York Avenue	New York	New York	United States	10021
4	Memorial Sloan-Kettering Cancer Center at Mercy Medical Center	Rockville Centre	New York	United States	11570
5	Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital	Sleepy Hollow	New York	United States

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Sanofi
• Genentech, Inc.

Investigators

• Principal Investigator: David Ilson, MD,PhD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan-Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00390416
• Other Study ID Numbers: 06-096; NCT00403468
• First Posted: Oct 19, 2006
• Last Update Posted: Mar 14, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: Metastatic; Gastroesophageal; Docetaxel; Cisplatin; Fluorouracil; Bevacizumab; Metastatic Gastroesophageal Adenocarcinoma; 06-096
• Additional relevant MeSH terms: Neoplasms; Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Leucovorin; Bevacizumab; Docetaxel; Fluorouracil

Study Results

Participant Flow

Arm/Group Title	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Arm/Group Description	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin: Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
Period Title: Overall Study
STARTED	48
COMPLETED	44
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Arm/Group Description	Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
Overall Participants	48
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	40 83.3%
>=65 years	8 16.7%
Sex: Female, Male (Count of Participants)
Female	14 29.2%
Male	34 70.8%
Region of Enrollment (participants) [Number]
United States	48 100%

Outcome Measures

1. Primary Outcome

Title	6 Month Progression Free Survival
Description	as measured from the start of the treatment to the date of either documentation of disease progression or death. As we have previously, we will define progression of disease as per RECIST criteria. As per RECIST criteria, any evidence of progression in non-measurable lesions, measurable lesions, or the development of new lesions, would qualify as disease progression .RECIST criteria as defined by CTEP (http://ctep.info.nih.gov/Policies).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Arm/Group Description	Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	79 164.6%

2. Secondary Outcome

Title	Patients With Measurable Disease the Confirmed Response Rate
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Arm/Group Description	Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
Measure Participants	39
Confirmed Response Rate	67 139.6%
Response Rate (proximal/GEJ tumors)	85 177.1%

3. Primary Outcome

Title	1-year Survival
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Arm/Group Description	Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
Measure Participants	39
Progression Free Survival	12
Overall Survival	16.8

Adverse Events

Arm/Group Title	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
Arm/Group Description	Bevacizumab 10mg/kg day 1 IV over 30 minutes Docetaxel 40mg/m2 day 1 IV over 1 hour Leucovorin 400mg/m2 day 1 IV over 30 minutes Fluorouracil 400mg/m2 IVP day 1 Fluorouracil 1000mg/m2 IVCI x 48 hours Cisplatin 40mg/m2 day 3 IV over 30 minutes
All Cause Mortality
	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
	Affected / at Risk (%)	# Events
Total	27/48 (56.3%)
Blood and lymphatic system disorders
Febrile neutropenia	2/48 (4.2%)	2
Anemia	1/48 (2.1%)	1
Cardiac disorders
Chest pain-cardiac	1/48 (2.1%)	1
Gastrointestinal disorders
Diarrhea	1/48 (2.1%)	1
Dysphagia	1/48 (2.1%)	1
Anal fistula	1/48 (2.1%)	1
Hemorrhage, Abdomen NOS	1/48 (2.1%)	1
Mucositis-Oral	3/48 (6.3%)	3
Nausea	4/48 (8.3%)	4
Rectal obstruction	1/48 (2.1%)	1
Small intestinal obstruction	1/48 (2.1%)	1
Abdominal pain	4/48 (8.3%)	4
Esophageal perforation	1/48 (2.1%)	1
Gastric perforation	1/48 (2.1%)	1
Vomiting	3/48 (6.3%)	4
General disorders
Death not assoc w CTCAE term-Disease prog NOS	3/48 (6.3%)	3
Fatigue	1/48 (2.1%)	1
Infections and infestations
Infection, other	3/48 (6.3%)	4
Injury, poisoning and procedural complications
Fracture	1/48 (2.1%)	1
Investigations
Bilirubin increased	1/48 (2.1%)	1
White blood cell decreased	1/48 (2.1%)	1
Neutrophil count decreased	8/48 (16.7%)	9
Platelet count decrease	1/48 (2.1%)	1
Metabolism and nutrition disorders
Anorexia	1/48 (2.1%)	1
Dehydration	6/48 (12.5%)	6
Hypokalemia	1/48 (2.1%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/48 (4.2%)	3
Nervous system disorders
Dizziness	1/48 (2.1%)	1
Syncope	1/48 (2.1%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/48 (2.1%)	1
Pneumonia	1/48 (2.1%)	1
Vascular disorders
Hypotension	2/48 (4.2%)	2
Thrombosis/thrombus/embolism	4/48 (8.3%)	4
Other (Not Including Serious) Adverse Events
	Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin
	Affected / at Risk (%)	# Events
Total	44/48 (91.7%)
Blood and lymphatic system disorders
Anemia	26/48 (54.2%)	241
Ear and labyrinth disorders
Tinnitus	4/48 (8.3%)	6
Gastrointestinal disorders
Diarrhea	13/48 (27.1%)	21
Dysphagia	4/48 (8.3%)	6
Mucositis-Oral	20/48 (41.7%)	37
Nausea	12/48 (25%)	24
Abdominal pain	3/48 (6.3%)	4
Vomiting	5/48 (10.4%)	11
General disorders
Fatigue	28/48 (58.3%)	104
Immune system disorders
Allergic reaction	6/48 (12.5%)	8
Investigations
Alanine aminotransferase increase	4/48 (8.3%)	6
Aspartate aminotransferase increase	5/48 (10.4%)	9
Creatinine increased	4/48 (8.3%)	8
White blood cell decreased	36/48 (75%)	197
Lymphocyte count decreased	26/48 (54.2%)	115
Neutrophil count decreased	34/48 (70.8%)	127
Platelet count decreased	11/48 (22.9%)	58
Metabolism and nutrition disorders
Anorexia	5/48 (10.4%)	7
Dehydration	8/48 (16.7%)	15
Hypomagnesemia	20/48 (41.7%)	112
Hypophosphatemia	30/48 (62.5%)	119
Hypokalemia	4/48 (8.3%)	7
Nervous system disorders
Peripheral sensory neuropathy	16/48 (33.3%)	54
Dysgeusia	4/48 (8.3%)	4
Skin and subcutaneous tissue disorders
Dry skin	3/48 (6.3%)	3
Hair loss/alopecia	3/48 (6.3%)	18
Rash: hand-foot skin reaction	3/48 (6.3%)	6
Vascular disorders
Thrombosis/thrombus/embolism	19/48 (39.6%)	21

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.