Phase II Prospective, Open Label Randomized Controlled Trial Comparing Standard of Care Therapy With and Without Sequential Cytoreductive Intervention for Patients With Metastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid (ctDNA) Levels
This is a randomized, open label, single-center, phase 2, randomized controlled trial of sequential cytoreductive intervention versus standard of care therapy for patients with intervenable oligometastatic (stage IV) cancer of the upper gastrointestinal (GI) tract and undetectable ctDNA at the time of randomization after a three-month induction chemotherapy period.
• Has a primary diagnosis of AJCC 8th Edition Stage IV esophageal or gastroesophageal adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma, duodenal, and ampullary adenocarcinoma.
• a) All participants must have confirmed histologic diagnosis of the primary tumor, which may be confirmed retrospectively by a radiologist if necessary.
• Has a primary tumor that must be locally resectable or can be treated definitively. Primary tumors included are esophageal, gastric, duodenal, ampullary, pancreatic, cholangiocarcinoma, and gall bladder carcinoma. Primary tumors should be resectable or treatable with consolidative radiotherapy or ablative therapy such as microwave ablation or trans-arterial chemo/radioembolization (cholangiocarcinomas).
• Has limited (2 sites) metastatic disease determined to be completely resectable or treatable with curative intention (see SOE) at the time of diagnosis. This includes:
‣ Up to five pulmonary metastases amenable to wedge resection (maximum of three wedge resections) or lobectomy (single lobectomy) or consolidative radiation/ablative therapy
⁃ Up to five hepatic metastases amenable to hepatectomy (segmentectomy, sectionectomy, sectorectomy, minor hepatectomy, not more than three segments), wedge resection requiring a minimum of 40% of liver parenchyma following resection based on future liver remnant or a combination of partial hepatectomy and microwave ablation or trans-arterial radioembolization (TARE).
⁃ Lymphatic metastases that are resectable or intervenable (limited to only two non-regional sites) (see Appendix 3).
⁃ Resectable peritoneal disease with a PCI of ≤6 and the ability to obtain a CC0 cytoreduction.
⁃ Distant metastasis must be limited to two of the above-mentioned sites (a-d).
⁃ If both pulmonary and liver metastasis are present (a, b), then a total of five lesions will be considered oligometastatic.
• Patients with resected primary tumors can be included if they present with oligometastases at least six months after the completion of treatment of primary tumor with curative intent.
• Has adequate organ function, as described below (see Appendix 4); all screening laboratory tests should be performed within 30 days prior to the first study intervention.
• Patients must have had two concordant negative tissue informed ctDNA tests measured at different timepoints and with the second being within 45 days prior to enrollment.
• Patients must have at least 4 months of prior effective systemic therapy.
• Has hemoglobin ≥ 8 g/dL.
• Has ANC ≥ 1500/uL.
• Has platelet count ≥ 75000/uL.
• Has total bilirubin ≤ 1.5 times the upper limit of normal (ULN).
• Has aspartate aminotransferase (AST) \& alanine aminotransferase (ALT) ≤ 5 times ULN.
• Has creatinine clearance ≥ 50 mL/min.
• Patient who is at least 18 years of age at the time of signing informed consent and less than 81 years of age at the time of signing informed consent.
• Has an ECOG performance status score 0-1 (see Appendix 6) at the time of randomization.
• A male participant must agree to use contraception (barrier birth control, abstinence) during the treatment period and for at least 95 days following completion, corresponding to time needed to eliminate any study intervention(s), and refrain from donating sperm during this period.
• A female participant of childbearing age is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use contraception (hormonal, barrier birth control, or abstinence) during the treatment period and for at least 95 days following completion. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately.
∙ Informed Consent
• The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for the Foundation for Blood Research (FBR). However, the participant may participate in the main study without participating in the FBR.