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Intraperitoneal Docetaxel in Combination with mFOLFOX6 for the Treatment of Gastric Cancer Patients with Peritoneal Carcinomatosis

Trial Status: Active

This phase I trial evaluates the side effects and best dose of intraperitoneal docetaxel when given together with intravenous combination chemotherapy (mFOLFOX6) in treating patients with gastric cancer that has spread to the peritoneal (abdominal) surface (peritoneal carcinomatosis). Docetaxel works by inhibiting DNA, RNA, and protein creation thus preventing the growth of tumor cells. mFOLFOX6 is a combination of oxaliplatin, leucovorin, and fluorouracil that work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) kills more tumor cells. Giving docetaxel directly into the abdomen (intraperitoneal) may result in more of the drug reaching the tumor cells. Giving intraperitoneal docetaxel and intravenous mFOLFOX6 chemotherapy may be effective in treating gastric cancer patients with peritoneal carcinomatosis.

Inclusion Criteria

  • Have histologically-confirmed gastric cancer (GC)-peritoneal carcinomatosis (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
  • Not have distant metastases as ruled out by an initial imaging (e.g. computed tomography [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
  • Absolute neutrophil count (ANC) >= 1,500 /mcL (within 7 days prior to protocol therapy)
  • Platelets >= 100,000/mcL (within 7 days prior to protocol therapy)
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (within 7 days prior to protocol therapy)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (within 7 days prior to protocol therapy) * Creatinine clearance should be calculated per institutional standard
  • Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 7 days prior to protocol therapy)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN (within 7 days prior to protocol therapy)
  • Albumin > 3.0 gm/dL (within 7 days prior to protocol therapy)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 7 days prior to protocol therapy)
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (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 (Siewert 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 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 nitrosoureas 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., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Patients receiving any medications or substances that are inhibitors or inducers of 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: * Congenital long QT syndrome * Corrected QT (QTc) interval >= 485 milliseconds * 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 * Other significant electrocardiogram (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 * 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 * 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 * Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multigated acquisition scan (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI) * 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) * Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes * 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 * Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers) * Patients taking drugs leading to significant QT prolongation * Evidence/history of coronary vasospasm
  • Any other condition that would render the patient to be unfit for the trial as deemed by the principal investigator (PI) or clinical team

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Fabian Mc. Johnston
Phone: 410-502-0197

PRIMARY OBJECTIVE:

I. To determine the safety of administering intraperitoneal docetaxel (IP DTX) in conjunction with the standard of care treatment regimen of intravenous modified (m) leucovorin, fluorouracil and oxaliplatin (FOLFOX6) in patients with primary gastric cancer with gross peritoneal carcinomatosis.

SECONDARY AND EXPLORATORY OBJECTIVES:

I. Assess the quality of life in patients undergoing study protocol with primary gastric cancer and gross peritoneal disease.

II. To estimate progression-free survival and overall survival in gastric cancer patients treated with IP DTX concurrently with systemic mFOLFOX6.

III. To estimate the response rate of IP DTX concurrently with systemic mFOLFOX6 in gastric cancer patients.

IV. To collect patient specimens into a tissue bank for future studies.

OUTLINE: This is a dose-escalation study of docetaxel.

Patients receive fluorouracil intravenously (IV) over 15 minutes on day 1, then continuously over 46 hours on days 1 and 2, leucovorin IV over 2 hours on day 1, oxaliplatin IV over 2 hours on day 1, and docetaxel intraperitoneally (IP) over 60 minutes on days 1 and 8. Treatment repeats every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with a minimal burden of disease (peritoneal cancer index [PCI] score =< 7) may undergo gastrectomy per standard of care.

After completion of study treatment, patients are followed up every 3 months for 5 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Fabian Mc. Johnston

  • Primary ID J1709
  • Secondary IDs NCI-2020-07534, CRMS-65773, IRB00162730
  • Clinicaltrials.gov ID NCT04583488