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

NCT03283761 | Completed Phase 2 Results FDA Drug

• 1 other identifier: BTCRC-GI15-015
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 8

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.

Conditions

Gastro-Esophageal Junction Adenocarcinoma; Gastric Cancer

Keywords

FOLFOX; Nab-Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate will be calculated by combining the number of subjects who achieve complete response and partial response per RECIST 1.1 criteria.Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to \<10 mm.

  From C1D1 until death or up to a maximum of 36 months

Secondary Outcomes (6)

• Overall Survival (OS)

  From C1D1 until death or up to a maximum of 52 months

• Progression-Free Survival (PFS)

  From C1D1 until death or up to a maximum of 36 months

• Time to Progression (TTP)

  From C1D1 until PD or up to a maximum of 36 months

• Number of Subjects Achieve Best Overall Response of CR, PR, SD and PD

  From C1D1 until PD or up to a maximum of 36 months

• Disease Control Rate (DCR)

  From C1D1 until PD or up to a maximum of 36 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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.

Drug: Nab-paclitaxel 150 mg/m^2; Drug: Oxaliplatin 85 mg/m^2; Drug: 5-FU 1200 mg/m^2 x 2 D; Drug: Leucovorin 400 mg/m^2

Interventions

Nab-paclitaxel 150 mg/m^2 DRUG

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

Also known as: Abraxane®

Treatment Arm

Oxaliplatin 85 mg/m^2 DRUG

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

Also known as: Eloxatin

Treatment Arm

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

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

Also known as: Adrucil, Fluorouracil

Treatment Arm

Leucovorin 400 mg/m^2 DRUG

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

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Al B. Benson, III, MD: lead
• Celgene Corporation: collaborator
• Big Ten Cancer Research Consortium: collaborator

Study Sites (8)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Univeristy of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Michigan State University

Lansing, Michigan, 48910, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Related Links

• Big Ten Cancer Research Consortium Website

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Oxaliplatin; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Clinical Data Analyst
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• Al B. Benson, MD

  Big Ten Cancer Research Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 14, 2017
• Study Start: September 21, 2017
• Primary Completion: December 27, 2022
• Study Completion: January 16, 2023
• Last Updated: February 6, 2024
• Results First Posted: February 6, 2024

Record last verified: 2024-01

Locations

US (8)