Clinical trial NCT02485834: FDG-PET Directed Treatment in Improving Response in Patients With Locally Advanced Stomach or Gastroesophageal Junction Cancer
Official title: Impact of Early FDG-PET Directed Intervention on Preoperative Therapy for Locally Advanced Gastric Cancer: A Random Assignment Phase II Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adenocarcinoma of the Gastroesophageal Junction
Gastric Adenocarcinoma
Gastric Cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-06-30
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II trial studies how well fludeoxyglucose F-18 (FDG)/positron emission tomography (PET) directed treatment improves response in patients with stomach or gastroesophageal junction cancer that has not spread past the stomach and is not responding to the usual treatment. PET scans are a different way to take pictures of cancer and can be used to look at how much energy (such as glucose) is being used by the cancer. Using PET scans early to monitor the success of treatment may allow doctors to measure response and change treatment accordingly.

Detailed description: Pre-registered patients receive standard pre-operative chemotherapy comprising epirubicin intravenously 50mg/m\^2 (IV) on day 1; oxaliplatin 130 mg/m\^2 IV or cisplatin 60 mg/m\^2 IV on day 1; and capecitabine 625 mg/m\^2 orally (PO) twice daily (BID) or fluorouracil 200 mg/m\^2/day IV continuously on days 1-21; and undergo FDG-PET following course 1 (days 15-19). Patients defined as FDG-PET non-responders are registered and randomized to 1 of 2 treatment arms.

Primary objective

To assess and compare the overall survival (OS) of patients with locally advanced gastric cancer classified as FDG-PET non-responders after one cycle of pre-operative chemotherapy randomly assigned to receive either salvage chemotherapy before and after surgery or immediate surgery followed by fluorouracil sensitized radiotherapy.

Secondary objectives

1. To assess and compare progression-free survival (PFS) between the treatment arms (Arms A and B).
2. To assess and compare R0 resection rate between the treatment arms (Arms A and B).
3. To assess and compare pathologic complete response (pCR) rate between the treatment arms (Arms A and B).
4. To assess the adverse events (AE) profile and safety of each treatment arm (Arms A and B), including post-operative mortality rate, 30-day post-operative targeted adverse events (i.e., dehiscence, significant infection, and re-operation rate).
5. To examine the changes of FDG-PET SUV induced by pre-operative chemotherapy at different time points (from baseline to completion of one cycle of treatment before randomization, and 2 cycles of salvage treatment) in patients randomized to salvage treatment arm (Arm B).
6. To collect measurement of fatigue and overall perception of QOL at registration of the study (Alliance registration QOL assessment study).

Eligibility criteria: Pre-Registration Eligibility Criteria

1. Documentation of Disease

   1.1 Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II, III)

   1.2 Pre-treatment clinical stage of T3-4N any M0 or T any N positive M0 as determined by laparoscopy, CT scan (or PET/CT), or endoscopic ultrasound (histologic confirmation of lymph involvement is not required). Therefore, patients can have measurable or non-measurable disease.

   1.3 Patients with T1-2N0M0 tumors or patients with metastatic disease are NOT eligible.
2. Patients must be eligible for curative intent surgical resection.
3. FDG Avid malignancy - Patients must have an FDG avid tumor(s). FDG avid tumors are defined as a primary tumor with an increased uptake in the region of the tumor that has an SUV of \> 5.0 or a tumor:liver SUV ratio of \> 1.5.
4. No prior history of congestive heart failure - NYHA class I to IV or known DPD deficiency
5. No current grade 2, 3, or 4 of neuropathy.
6. No known hypersensitivity to epirubicin, oxaliplatin and cisplatin, capecitabine and 5-flurouracil, docetaxel or irinotecan.
7. Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.

   7.1 Therefore, for women of childbearing potential only, a negative serum pregnancy test pregnancy test done ≤ 7 days prior to pre-registration is required.

   7.2 A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
8. Age ≥ 18 years
9. ECOG Performance Status 0 or 1
10. Required Initial Laboratory Values:

    * Absolute Neutrophil Count (ANC) ≥ 1,500/mm\^3
    * Platelet Count ≥ 100,000/mm\^3
    * Creatinine ≤ 1.5 x upper limit of normal (ULN)
    * Total Bilirubin ≤ 1.5 x ULN, except in patients with Gilbert's disease
    * AST and ALT ≤ 2.5 x ULN
    * Alkaline Phosphatase ≤ 2.5 x ULN

Registration Eligibility Criteria to Treatment Arms A or B

1. Patient must continue to be eligible for curative intent surgical resection.
2. Disease Progression: FDG avid malignancy that is classified as an FDG PET non- responder. PET non-responders are defined as having \< 35% reduction in the FDG uptake of the primary tumor when compared to baseline.
3. Concomitant Medications -

   3.1 Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this trial. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days prior to the start of study treatment.

   3.2 Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
4. Patient must have received only one cycle of the following regimens during the pre-registration time period and no other therapy for gastric or gastroesophageal junction cancer:

   * Epirubicin, Oxaliplatin, and Capecitabine
   * Epirubicin, Oxaliplatin, and Fluorouracil
   * Epirubicin, Cisplatin, and Capecitabine
   * Epirubicin, Cisplatin, and Fluorouracil
5. Toxicity recovery should include the following:

   * Grade ≤ 2 neuropathy
   * Grade ≤ 2 diarrhea
   * Grade ≤ 2 mucositis
6. Pre-registration chemotherapy given within 42 days of treatment (treatment meaning surgery if Arm A, chemotherapy if Arm B)

Primary outcomes:
measure: Overall Survival
timeFrame: Up to 3 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Up to 3 years
measure: Number of Patients Achieved R0 Resection During Surgery
timeFrame: At time of surgery
measure: Number of Patients Had Pathologic Complete Response
timeFrame: Up to 3 years
measure: Number of Participants Who Reported Grade 3 or Higher Adverse Events
timeFrame: Up to 30 days after completion of protocol treatment
Other outcomes:
measure: Change in FDG-PET SUV Measures
timeFrame: Up to 14 days prior to surgery
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Saint Helena
country: United States
facility: Saint Helena Hospital
state: California
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Newark
country: United States
facility: Regional Hematology and Oncology PA
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: 'Aiea
country: United States
facility: Hawaii Oncology Inc-Pali Momi
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Cancer Care Inc-POB II
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Cancer Care Inc-Liliha
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Oncology Inc-Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: The Cancer Center of Hawaii-Liliha
state: Hawaii
city: Post Falls
country: United States
facility: Kootenai Cancer Center
state: Idaho
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Geneva
country: United States
facility: Northwestern Medicine Cancer Center Delnor
state: Illinois
city: Warrenville
country: United States
facility: Northwestern Medicine Cancer Center Warrenville
state: Illinois
city: Mishawaka
country: United States
facility: Memorial Regional Cancer Center Day Road
state: Indiana
city: Richmond
country: United States
facility: Reid Health
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Edina
country: United States
facility: Fairview-Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Joplin
country: United States
facility: Freeman Health System
state: Missouri
city: Rolla
country: United States
facility: Delbert Day Cancer Institute at PCRMC
state: Missouri
city: Rolla
country: United States
facility: Saint John's Clinic-Rolla-Cancer and Hematology
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Great Falls
country: United States
facility: Benefis Healthcare- Sletten Cancer Institute
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc-Blue Ash
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital - Dayton
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Health Center
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Hospital
state: Ohio
city: Franklin
country: United States
facility: Atrium Medical Center-Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Springfield
country: United States
facility: Springfield Regional Medical Center
state: Ohio
city: Troy
country: United States
facility: Upper Valley Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Andrews
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Butternut
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Faris
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Eastside
state: South Carolina
city: Greer
country: United States
facility: Greenville Health System Cancer Institute-Greer
state: South Carolina
city: Seneca
country: United States
facility: Greenville Health System Cancer Institute-Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Greenville Health System Cancer Institute-Spartanburg
state: South Carolina
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
Study officials:
affiliation: Weill Medical College of Cornell University
name: Manish Shah, MD
role: STUDY_CHAIR
References: