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

• Sponsor: Al B. Benson, III, MD
• Collaborators: Celgene Corporation; Big Ten Cancer Research Consortium
• Information provided by (Responsible Party): Al B. Benson, III, MD, Big Ten Cancer Research Consortium

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Gastro-Esophageal Junction Adenocarcinoma; Gastric Cancer	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	Phase 2

Detailed Description:

All patients will receive FOLFOX-A every 14 days 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 8 weeks to evaluate response to treatment by RECIST Version 1.1 guidelines. Patients may continue to receive treatment until disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 39 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Masking Description: Open-Label
• Primary Purpose: Treatment
• Official Title: A Phase II Study of FOLFOX Combined With Nab-Paclitaxel (FOLFOX-A) in the Treatment of Metastatic or Advanced Unresectable Gastric, Gastro-Esophageal Junction Adenocarcinoma. Big Ten Cancer Research Consortium: BTCRC-GI15-015
• Actual Study Start Date: September 21, 2017
• Estimated Primary Completion Date: June 30, 2020
• Estimated Study Completion Date: June 30, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment Arm; All patients in Stage I (N=12) and Stage II (N=25) will receive FOLFOX-A every 14 days 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 8 weeks 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; Stage I (N=12), every 14 days Stage II (N= 25), every 14 days; Other Name: Abraxane®; Drug: Oxaliplatin 85 mg/m^2; Stage I (N= 12), every 14 days Stage II (N= 25), every 14 days; Other Name: Eloxatin; Drug: 5-FU 1200 mg/m^2 x 2 D; Stage I (N= 12), every 14 days Stage II (N= 25), every 14 days; Other Names: Adrucil; Fluorouracil; Drug: Leucovorin 400 mg/m^2; Stage I (N= 12), every 14 days Stage II (N= 25), every 14 days

Outcome Measures

Primary Outcome Measures :

1. Overall Objective Response Rate [ Time Frame: 2 years ]
   partial or complete response of FOLFOX combined with nab-paclitaxel (FOLFOX-A) in patients with advanced gastric, gastroesophageal junction adenocarcinoma

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: 2 years ]
   will be estimated using the method of Kaplan-Meier and univariate testing will be done via the log rank test (median time to event)
2. Progression-Free Survival (PFS) [ Time Frame: 2 years ]
   will be estimated using the method of Kaplan-Meier and univariate testing will be done via the log rank test (median time to event)
3. Time to Progression (TTP) [ Time Frame: 2 years ]
   will be estimated using the method of Kaplan-Meier and univariate testing will be done via the log rank test (median time to event)
4. Best Overall Response Rate (ORR) [ Time Frame: 2 years ]
   will be summarized by count and percent of subjects with each ordinal response analyzed by Cochran-Mantel-Hanzel test
5. Best Disease Control Rate (DCR) [ Time Frame: 2 years ]
   will be summarized by count and percent of subjects with each ordinal response analyzed by Cochran-Mantel-Hanzel test
6. Adverse Events [ Time Frame: 2 years ]
   grade 3 and 4 adverse events defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Subject must meet all of the following applicable inclusion criteria to participate in this study:

• Written informed consent and HIPAA authorization for release of personal health information.
• 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.
• Measurable 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/mm^3 (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to laboratory sample), Hemoglobin > 9.0g/dL and ANC > 1,500 cells/mm^3.
  • 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 IP therapy (including dose interruptions), and while on study medication or for a longer period if required by local regulations 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.

Exclusion Criteria:

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

• Prior systemic treatment.
• 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.
• 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.

Contacts and Locations

Contacts

Contact: Dylan Cregar; 317-634-5842 ext 38; dcregar@hoosiercancer.org

Contact: Al B. Benson,, MD; 312-695-6180; a-benson@northwestern.edu

Locations

United States, Illinois

Northwestern University Feinberg School of Medicine; Recruiting

Chicago, Illinois, United States, 60611

Contact: Victoria Maurer 312-695-3818 victoria.maurer@northwestern.edu

Principal Investigator: Al Benson, MD

Univeristy of Illinois Cancer Center; Recruiting

Chicago, Illinois, United States, 60612

Contact: Alyssa Secreto 312-413-1069 asecre2@uic.edu

Principal Investigator: Rozina Chowdhery, MD

Northwestern Medicine Lake Forest Hospital; Recruiting

Lake Forest, Illinois, United States, 60045

Contact: Valerie Nelson 847-582-2134 cancertrials@northwestern.edu

United States, Michigan

Michigan State University; Recruiting

Lansing, Michigan, United States, 48910

Contact: Kimberly Wright 517-975-9532 Kimberly.Wright@hc.msu.edu

Principal Investigator: Jatin Rana, MD

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Julie Madsen 612-625-0761 mads0056@umn.edu

Principal Investigator: Emil Lou, MD

United States, New Jersey

Rutgers Cancer Institute of New Jersey; Recruiting

New Brunswick, New Jersey, United States, 08903

Contact: Tracie Saunders 732-235-8861 ks13@cinj.rutgers.edu

Principal Investigator: Howard Hochster, MD

United States, Wisconsin

University of Wisconsin; Recruiting

Madison, Wisconsin, United States, 53705

Contact: Erin Clements 608-265-2857 eclements@wisc.edu

Principal Investigator: Nataliya Uboha, MD

Sponsors and Collaborators

Al B. Benson, III, MD

Celgene Corporation

Big Ten Cancer Research Consortium

Investigators

• Study Chair: Al B. Benson, MD; Big Ten Cancer Research Consortium

More Information

Additional Information:

Big Ten Cancer Research Consortium Website 

• Responsible Party: Al B. Benson, III, MD, Sponsor-Investigator, Big Ten Cancer Research Consortium
• ClinicalTrials.gov Identifier: NCT03283761 History of Changes
• Other Study ID Numbers: BTCRC-GI15-015
• First Posted: September 14, 2017
• Last Update Posted: August 14, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Al B. Benson, III, MD, Big Ten Cancer Research Consortium:

FOLFOX; Nab-Paclitaxel

Additional relevant MeSH terms:

Adenocarcinoma; Esophageal Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Paclitaxel; Albumin-Bound Paclitaxel; Oxaliplatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action