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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02485834
• Other study ID #: A021302
• Secondary ID: U10CA180821NCI-2
• Status: Terminated
• Phase: Phase 2
• Start date: August 2015
• Est. completion date: August 2018

Study information

• Verified date: September 2019
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: August 2018
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Gastric Adenocarcinoma
• Gastric Cancer
• Stomach Neoplasms

Intervention

Procedure:
• FDG-PET

• surgery

Drug:
• 5-FU
200 mg/m^2/day IV
• capecitabine
oral 800 mg/m^2 BID
• docetaxel
30 mg/m^2 IV
• Irinotecan
50 mg/m^2 IV

Radiation:
• 3D-CRT

• IMRT

Locations

Country	Name	City	State
United States	Hawaii Oncology Inc-Pali Momi	'Aiea	Hawaii
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Medical University of South Carolina	Charleston	South Carolina
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii
United States	Hawaii Oncology Inc-Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Freeman Health System	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kettering Medical Center	Kettering	Ohio
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Regional Hematology and Oncology PA	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Saint Helena Hospital	Saint Helena	California
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in FDG-PET SUV Measures		Up to 14 days prior to surgery
Primary	Overall Survival	Overall survival is defined as the time from date of randomization to death due to any cause.	Up to 3 years
Secondary	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
Secondary	Number of Patients Achieved R0 Resection During Surgery	The number of patients achieved R0 resection during surgery	At time of surgery
Secondary	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
Secondary	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