FOLFOX-A in the Treatment of Metastatic or Advanced Unresectable Gastric, Gastro-Esophageal Junction Adenocarcinoma

NCT ID: NCT03283761

Last Updated: 2024-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-21
• Study Completion Date: 2023-01-16

Brief Summary

This is an open label, single-arm phase II, multi-institutional trial to evaluate the efficacy and safety of the combination of nab-paclitaxel and FOLFOX (FOLFOX-A) as first line therapy for patients diagnosed with histologically-confirmed advanced gastric/GEJ adenocarcinoma.

Detailed Description

All patients will receive FOLFOX-A on days 1 and 15 of each cycle (1 cycle = 28 days). Nab-paclitaxel will be given at a dose of 150 mg/m2 IV over 30 minutes, followed by oxaliplatin IV 85 mg/m2 and leucovorin IV 400 mg/m2 over 2 hours, and 5-FU as a continuous IV infusion over Day 1 and Day 2 (for a total dose of 2400mg/m2 over 46-48 hours.). Radiographic assessment will be performed at baseline and every other cycle (starting with Cycle 3) to evaluate response to treatment by RECIST Version 1.1 guidelines. Patients may continue to receive treatment until disease progression or unacceptable toxicity.

Conditions

Gastro-Esophageal Junction Adenocarcinoma; Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

All patients in Stage I (N=12) and Stage II (N=25) will receive FOLFOX-A on days 1 and 15 of each cycle (1 cycle = 28 days). Nab-paclitaxel will be given at a dose of 150 mg/m\^2 IV over 30 minutes, followed by oxaliplatin IV 85 mg/m\^2 and leucovorin IV 400 mg/m\^2 over 2 hours, and 5-FU as a continuous IV infusion over Day 1 and Day 2 (for a total dose of 2400mg/m\^2 over 46-48 hours.). Radiographic assessment will be performed at baseline and every other cycle (starting with Cycle 3) to evaluate response to treatment by RECIST Version 1.1 guidelines. Patients may continue to receive treatment until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Nab-paclitaxel 150 mg/m^2

Intervention Type: DRUG

Stage I (N=12), on day 1 and day 15 Stage II (N= 25), on day 1 and day 15

Oxaliplatin 85 mg/m^2

Intervention Type: DRUG

Stage I (N= 12), on day 1 and day 15 Stage II (N= 25), on day 1 and day 15

5-FU 1200 mg/m^2 x 2 D

Intervention Type: DRUG

Stage I (N= 12), on day 1 and day 15-16 Stage II (N= 25),on day 1 and day 15-16

Leucovorin 400 mg/m^2

Intervention Type: DRUG

Stage I (N= 12),on day 1 and day 15 Stage II (N= 25), on day 1 and day 15

Interventions

Nab-paclitaxel 150 mg/m^2

Stage I (N=12), on day 1 and day 15 Stage II (N= 25), on day 1 and day 15

Intervention Type: DRUG

Oxaliplatin 85 mg/m^2

Stage I (N= 12), on day 1 and day 15 Stage II (N= 25), on day 1 and day 15

Intervention Type: DRUG

5-FU 1200 mg/m^2 x 2 D

Stage I (N= 12), on day 1 and day 15-16 Stage II (N= 25),on day 1 and day 15-16

Intervention Type: DRUG

Leucovorin 400 mg/m^2

Stage I (N= 12),on day 1 and day 15 Stage II (N= 25), on day 1 and day 15

Intervention Type: DRUG

Other Intervention Names

Abraxane®; Eloxatin; Adrucil; Fluorouracil

Eligibility Criteria

Inclusion Criteria

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Histologically-confirmed advanced or metastatic unresectable gastric carcinoma, or adenocarcinoma of the gastroesophageal junction.
• Prior neoadjuvant or adjuvant chemotherapy, hormonal therapy, immunotherapy, radiation or chemoradiotherapy must have been completed at least 6 months prior to documented recurrence or metastatic disease. NOTE: patients must not have received previous systemic treatment for metastatic disease.
• Evaluable disease according to RECIST v1.1 for solid tumors, within 28 days prior to registration.
• Demonstrate adequate organ function as described below; all screening labs to be obtained within 28 days prior to registration.

• Bilirubin < 1.5 mg/dL
• Patients must have adequate liver function: AST and ALT < 2.5 x upper limit of normal, alkaline phosphatase < 2.5 x upper limit of normal, unless bone or liver metastasis is present (≤5 x upper limit of normal).
• Patients must have adequate bone marrow function: Platelets >100,000 cells/mm3 (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample), Hemoglobin > 9.0g/dL and ANC > 1,500 cells/mm3.
• Patients must have adequate renal function: creatinine <1.5 mg/dL or creatinine clearance ≥60mL/min is recommended; however, institutional norms are acceptable.
• Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must:

• Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use and be able to comply with effective contraception without interruption 28 days prior to starting investigational product (IP), and while on study medication (including dose interruptions) and for 30 days following the last dose of IP; and
• Have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing prior to each treatment and after the end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.
• Male subjects must practice true abstinence* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following IP discontinuation, even if he has undergone a successful vasectomy.

• NOTE: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].

Exclusion Criteria

Subjects meeting any of the criteria below may not participate in the study:

• Her-2 positive gastric tumor.
• Treatment with any investigational products within 28 days prior to study registration.
• Preexisting peripheral neuropathy is not allowed from any cause.
• Known history of Human Immunodeficiency Virus (HIV) or Hepatitis C (baseline testing is not required).
• Patients with active sepsis or pneumonitis
• 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 trial registration 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 registration.
• Known hypersensitivity to fluorouracil (5-FU), oxaliplatin, or other platinum agents.
• Known hypersensitivity to nab-paclitaxel or any of its excipients.
• History of slowly progressive dyspnea and unproductive cough, or pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis or multiple allergies. See section 6.5.1.
• Has known dihydropyrimidine dehydrogenase deficiency (DPD) deficiency (testing not required)
• Ongoing or active infection requiring systemic treatment (must be afebrile for ≥ 48 hours prior to study registration)
• Uncontrolled intercurrent illness including, but not limited to any of the following:

• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Known additional malignancy within the past 3 years. Exceptions include treated localized basal cell or squamous cell carcinoma of the skin, in situ cervical or vulvar carcinoma that has undergone potentially curative therapy, superficial bladder tumors (Ta, Tis & T1), ductal carcinoma in situ (DCIS) of the breast and low grade prostate cancer (Gleason sore 6). Any cancer curatively treated > 3 years prior to registration with no clinical evidence of recurrence is permitted.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Big Ten Cancer Research Consortium

OTHER

Sponsor Role: collaborator

Al B. Benson, III, MD

OTHER

Sponsor Role: lead

Responsible Party

Al B. Benson, III, MD

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Al B. Benson, MD

Role: PRINCIPAL_INVESTIGATOR

Big Ten Cancer Research Consortium

Locations

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Univeristy of Illinois Cancer Center

Chicago, Illinois, United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Michigan State University

Lansing, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.bigtencrc.org

Big Ten Cancer Research Consortium Website

Other Identifiers

BTCRC-GI15-015

Identifier Type: -

Identifier Source: org_study_id