E-Newsletter - February 2017

Alliance Trials explores to use of PET scans to direct therapy for gastric cancers

Advanced Gastric Cancer | Alliance A021302
Impact of Early FDG-PET Directed Intervention on Preoperative Therapy for Locally Advanced Gastric Cancer: A Random Assignment Phase II Study

Across all treatment strategies, patients with locally advanced gastric cancer have a 10 to 15 percent absolute improvement in survival over surgery alone when additional treatment is prescribed. The limited benefit of adjuvant therapy is likely due to the persistence of microscopic disease that was not eradicated by the additional therapy. Based on numerous studies, it has also been established that a good fludeoxyglucose F-18 (FDG)/positron emission tomography (PET) response, which can be identified early following the initiation of therapy, is associated with improved patient survival. However, it remains unresolved whether or not FDG-PET can be used as a barometer for the response in micro-metastatic disease. Specifically, does a good FDG-PET response simply reflect a tumor with better underlying biology that was destined not to recur, or does a good FDG-PET response indicate a higher likelihood that micro-metastases were killed? If the latter is true, then patients with a poor FDG-PET response to chemotherapy (i.e., associated with a higher chance of recurrence) may then be salvaged with alternative treatment. Alliance A021302 will test this question directly.

In patients who are classified as FDG-PET non-responders, Alliance researchers will examine the utility of salvage therapy versus standard of care. If an improvement in FDG-PET response and survival in FDG-PET non-responding patients who receive salvage therapy are demonstrated, it would support two important concepts that would advance the field of gastric cancer research: (1) that FDG-PET may be used as a surrogate for response in micro-metastatic disease, and (2) early intervention with salvage chemotherapy is meaningful. Alternatively, if salvage therapy does not improve patient outcomes in FDG-PET non-responders, it would suggest that early FDG-PET response may be only a prognostic marker, identifying tumors with better biology that are destined to do well, or that the salvage treatment options are presently inadequate.

The primary objective of the Alliance A021302 study is to assess and compare the overall survival 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. Using PET scans early to monitor the success of treatment may allow doctors to measure response and change treatment accordingly. About 162 people will participate in this study.

Pre-registered patients will receive standard pre-operative chemotherapy comprising epirubicin hydrochloride, oxaliplatin or cisplatin, and capecitabine or fluorouracil, and will undergo FDG-PET. Patients defined as FDG-PET non-responders will be registered and randomized to one of two groups. Patients in Group 1 will undergo surgery within 42 days of completion of pre-registration chemotherapy, receive fluorouracil and capecitabine, and undergo 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy. Patients in Group 2, beginning within 28 days of pre-registration chemotherapy, will receive docetaxel and irinotecan hydrochloride followed by surgery. Patients will also undergo FDG-PET prior planned surgery. After surgery, patients receive additional docetaxel and irinotecan hydrochloride. After completion of study treatment, patients will be followed for five years at various intervals.

To be eligible for this study (Alliance A021302), patients must meet several criteria, including but not limited to the following:

Pre-registration

·              ·      Patients must have histologically diagnosed advanced gastric cancer (Siewert type II, III).

·      Pre-treatment clinical stage of primary tumor (T)3-4 lymph nodes (N) any metastasis (M) 0 or T any N positive M0 as determined by laparoscopy, CT scan (or PET/CT), or endoscopic ultrasound; patients can have measurable or non-measurable disease

·      Patients with T1-2N0M0 tumors or patients with metastatic disease are not eligible

·      Patients must be eligible for curative intent surgical resection

·      FDG avid malignancy; patients must have an FDG avid tumor(s)

Registration

·      Patient must continue to be eligible for curative intent surgical resection

·      Disease progression: FDG avid malignancy that is classified as an FDG PET non-responder

·      PET non-responders are defined as having less than 35 percent reduction in the FDG uptake of the primary tumor when compared to baseline.

To learn more about this study, refer to the study protocol (Alliance A021302), which can be found on the CTSU menu (ctsu.org) and includes complete information on the trial design, treatment plan and patient eligibility. The Alliance Study Chair is Manish A. Shah MD, Weill Medical College of Cornell University, e-mail: mas9313@med.cornell.edu. Also see ClinicalTrial.gov Identifier: NCT02485834.


 

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