Clinical Trials /

Intraperitoneal Docetaxel in Combination With mFOLFOX6 for Gastric Cancer Patients With Peritoneal Carcinomatosis

NCT04583488

Description:

This is a single-center, open-label, non-randomized, uncontrolled Phase 1 study of intraperitoneal docetaxel in combination with systemic mFOLFOX6 for patients who have gastric cancer with gross peritoneal carcinomatosis (GC-PC).

Related Conditions:
  • Peritoneal Carcinomatosis
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Intraperitoneal Docetaxel in Combination With mFOLFOX6 for Gastric Cancer Patients With Peritoneal Carcinomatosis
  • Official Title: A Phase I Study of Intraperitoneal Docetaxel in Combination With 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) for Gastric Cancer Patients With Peritoneal Carcinomatosis

Clinical Trial IDs

  • ORG STUDY ID: IRB00162730
  • NCT ID: NCT04583488

Conditions

  • Peritoneal Carcinomatosis

Interventions

DrugSynonymsArms
Intraperitoneal docetaxelTaxotereIntraperitoneal docetaxel

Purpose

This is a single-center, open-label, non-randomized, uncontrolled Phase 1 study of intraperitoneal docetaxel in combination with systemic mFOLFOX6 for patients who have gastric cancer with gross peritoneal carcinomatosis (GC-PC).

Detailed Description

      Gastric cancer (GC) is one of the leading causes of cancer-related deaths in the United
      States and has a five-year survival of 40% after surgical resection. Metastatic gastric
      cancer has an even poorer prognosis and most patients die within the first year of diagnosis.
      Most patients are diagnosed in advanced stages of the disease due to non-specific or lack of
      symptomatology and treatment options are then limited to systemic chemotherapy. The
      peritoneum is the most frequent site of metastasis as well as cancer recurrence. Peritoneal
      Carcinomatosis (PC) results in adverse clinical sequelae and is ultimately responsible for
      60% of all gastric cancer-related deaths. While visceral metastases originating from primary
      gastric cancer are relatively chemosensitive, peritoneal carcinomatosis is particularly
      challenging to treat because of inadequate drug delivery from systemic circulation. The
      primary purpose of this trial is to determine the safety of administering intraperitoneal
      docetaxel in conjunction with the standard of care treatment regimen of intravenous mFOLFOX6
      (5-Fluorouracil, leucovorin, and oxaliplatin) in patients with primary gastric cancer with
      gross peritoneal carcinomatosis.
    

Trial Arms

NameTypeDescriptionInterventions
Intraperitoneal docetaxelExperimentalParticipants will receive intraperitoneal docetaxel combined with intravenous mFOLFOX6. A standard 3 + 3 dose escalation design will be used according to the dose escalation plan.
  • Intraperitoneal docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Have histologically-confirmed GC-PC by diagnostic laparoscopy who have not undergone
             chemotherapy for metastatic/recurrent disease.

          -  Be willing and able to provide written informed consent/assent for the trial.

          -  Be ≥ 18 years of age on day of signing informed consent.

          -  Not have distant metastases as ruled out by an initial imaging (e.g. CT
             Chest/Abdomen/Pelvis with contrast), positron emission tomography (PET scan). Any
             metastasis in distant organs other than the peritoneum will exclude the patient from
             this study.

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale at study entry.

          -  Demonstrate adequate organ function. All screening labs should be performed within 7
             days prior to protocol therapy.

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication. Subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year.

          -  Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 120 days after the last dose of study therapy.

          -  Willingness to undergo intraperitoneal port placement

        Exclusion Criteria:

          -  Has gastric cancer involving the distal esophagus above the gastroesophageal (GE)
             junction (Siewart type 1, proximally), or second portion of the duodenum (distally).

          -  Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of
             treatment.

          -  Has a tumor positive for human epidermal growth factor receptor 2 (HER2) staining.

          -  Has had prior surgery with dense intra-abdominal adhesions

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          -  Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
             recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 4 weeks (6 weeks for nitrosureas or mitomycin C) prior to study Day 1 or who
             has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a
             previously administered agent.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy.

          -  Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.

          -  Has an active infection requiring antibiotic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has any other medical condition, including mental illness or substance abuse, deemed
             by the Investigator to be likely to interfere with a patient's ability to sign
             informed consent, cooperate and participate in the study, or interfere with the
             interpretation of the results.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C virus (e.g.,
             Hepatitis C virus RNA [qualitative] is detected).

          -  Patients receiving any medications or substances that are inhibitors or inducers of
             Cytochrome P450 3A4 (CYP 3A4) are ineligible. Investigator can change to a similar
             agent that is a non-CYP3A4 inhibitor/inducer with a washout period of 1 week.

          -  Patients with known hypersensitivity to any of the components of docetaxel or
             mFOLFOX6.

          -  Patients who received pelvic or abdominal radiotherapy.

          -  Peripheral neuropathy ≥ Grade 2.

          -  History of allogeneic transplant.

          -  Any known cardiac abnormalities, in accordance with mFOLFOX6 guidelines, such as:

             i. Congenital long QT syndrome. ii. Corrected QT (QTc) interval ≥ 485 milliseconds;
             iii. Myocardial infarction within 6 months of Cycle 1, Day 1 (C1D1). Subjects with a
             history of myocardial infarction between 6 and 12 months prior to C1D1 who are
             asymptomatic and have had a negative cardiac risk assessment (treadmill stress test,
             nuclear medicine stress test, or stress echocardiogram) since the event may
             participate; iv. Other significant ECG abnormalities including 2nd degree
             atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular
             rate less than 50 beats/min) Trial Treatments.

             v. Symptomatic coronary artery disease (CAD), e.g., angina. In any patient in whom
             there is doubt, the patient should have a stress imaging study and, if abnormal,
             angiography to define whether or not CAD is present; vi. An ECG recorded at screening
             showing evidence of cardiac ischemia (ST depression, depression of ≥2 mm, measured
             from isoelectric line to the ST segment). If in any doubt, the patient should have a
             stress imaging study and, if abnormal, angiography to define whether or not CAD is
             present; vii. Congestive heart failure (CHF) that meets New York Heart Association
             (NYHA) Class II to IV definitions (see Appendix B) and/or ejection fraction <40% by
             multigated acquisition (MUGA) scan or <50% by echocardiogram and/or MRI; viii. A known
             history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF),
             Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic
             implantable cardioverter defibrillator (AICD); ix. Hypertrophic cardiomegaly or
             restrictive cardiomyopathy from prior treatment or other causes; x. Uncontrolled
             hypertension, i.e., blood pressure (BP) of ≥160/95; patients who have a history of
             hypertension controlled by medication must be on a stable dose (for at least one
             month) and meet all other inclusion criteria; or xi. Any cardiac arrhythmia requiring
             an anti-arrhythmic medication (excluding stable doses of beta-blockers) xii. Patients
             taking drugs leading to significant QT prolongation xiii. Evidence / history of
             coronary vasospasm.

          -  Any other condition that would render the patient to be unfit for the trial as deemed
             by the PI or clinical team.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:20 weeks
Safety Issue:
Description:To determine the Maximum Tolerated Dose (MTD) of intraperitoneal docetaxel in conjunction with the standard of care treatment regimen of intravenous mFOLFOX6 in patients with primary gastric cancer with gross peritoneal carcinomatosis

Secondary Outcome Measures

Measure:Progression-Free Survival
Time Frame:20 weeks
Safety Issue:
Description:Progression-free survival rate at 20 weeks, which is defined as the percentage of patients alive and free of disease progression at 20 weeks.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Johns Hopkins University

Trial Keywords

  • gastric cancer
  • Peritoneal Surface Malignancies

Last Updated

October 5, 2020