FDG-PET Directed Treatment in Improving Response in Patients With Locally Advanced Stomach or Gastroesophageal Junction Cancer

Impact of Early FDG-PET Directed Intervention on Preoperative Therapy for Locally Advanced Gastric Cancer: A Random Assignment Phase II Study

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.

Study Overview

• Status: Terminated
• Conditions: Gastric Cancer; Gastric Adenocarcinoma; Adenocarcinoma of the Gastroesophageal Junction
• Intervention / Treatment: Procedure: surgery; Procedure: FDG-PET; Radiation: IMRT; Drug: 5-FU; Drug: capecitabine; Radiation: 3D-CRT; Drug: docetaxel; Drug: Irinotecan

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).

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Saint Helena, California, United States, 94574
      • Saint Helena Hospital
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Newark, Delaware, United States, 19713
      • Regional Hematology and Oncology PA
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Hawaii Oncology Inc-Pali Momi
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Cancer Care Inc-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc-POB II
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Oncology Inc-Kuakini
  • Idaho
    • Post Falls, Idaho, United States, 83854
      • Kootenai Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Geneva, Illinois, United States, 60134
      • Northwestern Medicine Cancer Center Delnor
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine Cancer Center Warrenville
  • Indiana
    • Mishawaka, Indiana, United States, 46545
      • Memorial Regional Cancer Center Day Road
    • Richmond, Indiana, United States, 47374
      • Reid Health
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Saint John's Clinic-Rolla-Cancer and Hematology
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc-Blue Ash
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Andrews
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Butternut
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A - surgery, chemotherapy and radiation therapy; Patients undergo surgery within 42 days of completion of pre-registration chemotherapy. Beginning within 49 days of surgery, patients receive 5-FU IV continuously and capecitabine PO BID on days 1-7, and undergo 3D-CRT or IMRT QD on days 1-5. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity.	Procedure: surgery; Radiation: IMRT; Drug: 5-FU; 200 mg/m^2/day IV; Drug: capecitabine; oral 800 mg/m^2 BID; Radiation: 3D-CRT
Experimental: Arm B - surgery, chemotherapy and FDG-PET; Beginning within 28 days of day 1 of pre-registration chemotherapy, patients receive docetaxel IV and irinotecan IV on days 1 and 8. Treatment repeats every 3 weeks for 2 courses. Beginning within 42 days of completion of docetaxel and irinotecan, patients undergo surgery. Patients also undergo FDG-PET within 14 days of planned surgery. Beginning within 60 days after surgery, patients receive 3 additional courses of docetaxel and irinotecan hydrochloride courses in the absence of disease progression or unacceptable toxicity.	Procedure: surgery; Procedure: FDG-PET; Drug: docetaxel; 30 mg/m^2 IV; Drug: Irinotecan; 50 mg/m^2 IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival is defined as the time from date of randomization to death due to any cause.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.	Up to 3 years
Number of Patients Achieved R0 Resection During Surgery	The number of patients achieved R0 resection during surgery	At time of surgery
Number of Patients Had Pathologic Complete Response	The number of patients had pathologic complete response (pCR). (pCR is defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined.)	Up to 3 years
Number of Participants Who Reported Grade 3 or Higher Adverse Events	The number of patients who reported grade 3 or higher Adverse Events according to Common Terminology Criteria for Adverse Events version 4.0.	Up to 30 days after completion of protocol treatment

Other Outcome Measures

Outcome Measure	Time Frame
Change in FDG-PET SUV Measures	Up to 14 days prior to surgery

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Manish Shah, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: June 25, 2015
• First Submitted That Met QC Criteria: June 26, 2015
• First Posted (Estimate): June 30, 2015

Study Record Updates

• Last Update Posted (Actual): September 11, 2019
• Last Update Submitted That Met QC Criteria: September 10, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Docetaxel; Capecitabine; Irinotecan
• Other Study ID Numbers: A021302; U10CA180821 (U.S. NIH Grant/Contract); NCI-2014-02566 (Registry Identifier: NCI Clinical Trials Reporting Office)