Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Therapy With and Without Sequential Cytoreductive Interventions for Patients With Metastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid (ctDNA) Levels
Overview
- Phase
- Phase 2
- Intervention
- Video-Assisted Thoracic Surgery (VATS)
- Conditions
- Metastatic Cancer
- Sponsor
- University of Chicago
- Primary Endpoint
- Progression Free Survival
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
This study is designed for participants who have cancer of the upper gastrointestinal (GI) tract such as cancer of the esophagus, stomach, duodenum (the initial portion of your small intestine), pancreas, bile duct (Cholangiocarcinoma), ampulla, or gall bladder with limited sites of spread (metastases). Doctors leading this study are looking to see if treating the disease using sequential procedures (more than one procedure given one after another) such as surgeries or radiation can lead to better survival and if these surgeries, combined with standard of care treatment, are safe for the treatment of upper GI cancers.
Detailed Description
This study is designed for participants who have cancer of the upper gastrointestinal (GI) tract such as cancer of the esophagus, stomach, duodenum (the initial portion of your small intestine), pancreas, bile duct (Cholangiocarcinoma), ampulla, or gall bladder with limited sites of spread (metastases). Doctors leading this study are looking to see if treating the disease using sequential procedures (more than one procedure given one after another) such as surgeries or radiation can lead to better survival and if it is safe for the treatment of upper GI cancers. The purpose of the proposed study is to identify a group of patients with metastatic cancer of the upper GI and biliary tract that may benefit from sequential procedures such as surgeries or radiation compared to the current standard of care chemotherapy treatment alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A participant will be eligible for inclusion in the study if the participant:
- •Has a newly diagnosed primary diagnosis of American Joint Committee of Cancer (AJCC) 8th Edition Stage IV esophageal or gastroesophageal adenocarcinoma, gastric adenocarcinoma, pancreatic/ampullary adenocarcinoma, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma gallbladder adenocarcinoma, duodenal, and ampullary adenocarcinoma.
- •All participants must have confirmed histologic diagnosis of the primary tumor
- •Excludes patients with bone and brain metastasis (See exclusion criteria)
- •Has a primary tumor that must be locally resectable or can be treated definitively (see preferred intervention sequence). 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 treatment algorithm) at the time of diagnosis (before induction chemotherapy). This includes:
- •Up to 5 pulmonary metastasis amenable to wedge resection (maximum of 3 wedge resections) or lobectomy (single lobectomy) or consolidative radiation/ablative therapy
- •Up to 5 hepatic metastasis amenable to hepatectomy (segmentectomy, sectionectomy, sectorectomy, minor hepatectomy (not more than 3 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).
- •Resectable peritoneal disease with a PCI of \<6 and the ability to obtain a CC0 cytoreduction.
Exclusion Criteria
- •The participant must be excluded from the study if the participant:
- •Medical Conditions
- •Has a positive urine pregnancy test within 3 days prior to randomization or treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Note: In the event that 3 days have elapsed between the screening pregnancy test and the first dose of study intervention, another pregnancy test (urine or serum) must be performed and must be negative for the participant to start receiving study medication.
- •Has hypoxia as defined by pulse oximeter reading \<92% at rest or requires intermittent or chronic supplemental oxygen.
- •Has a known additional malignancy that is progressing or has required active treatment within the past three years.
- •Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- •Has known central nervous system (CNS) metastasis and/or carcinomatous meningitis.
- •Has known osseous metastasis.
- •Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from treatment initiation, or New York Heart Association Class III or IV congestive heart failure. Medially controlled arrhythmia stable on medication is permitted.
Arms & Interventions
Arm A - Participants Who Receive Sequential Procedures
If you are assigned to this arm, study doctors will sequentially remove and treat all visible cancer spots with surgery, radiation, ablation, or other procedures. These interventions might include surgical removal of the diseased part of your lung, liver, lymph nodes, and/or the lining of your belly. In addition, if surgery could not be done, we could treat these diseased spots with other modalities such as radiation and/or radiofrequency/microwave ablation. If you're selected to be in this arm, the type of procedure you receive will vary based on your cancer and what the study doctor recommends for treatment.
Intervention: Video-Assisted Thoracic Surgery (VATS)
Arm A - Participants Who Receive Sequential Procedures
If you are assigned to this arm, study doctors will sequentially remove and treat all visible cancer spots with surgery, radiation, ablation, or other procedures. These interventions might include surgical removal of the diseased part of your lung, liver, lymph nodes, and/or the lining of your belly. In addition, if surgery could not be done, we could treat these diseased spots with other modalities such as radiation and/or radiofrequency/microwave ablation. If you're selected to be in this arm, the type of procedure you receive will vary based on your cancer and what the study doctor recommends for treatment.
Intervention: Lobectomy
Arm A - Participants Who Receive Sequential Procedures
If you are assigned to this arm, study doctors will sequentially remove and treat all visible cancer spots with surgery, radiation, ablation, or other procedures. These interventions might include surgical removal of the diseased part of your lung, liver, lymph nodes, and/or the lining of your belly. In addition, if surgery could not be done, we could treat these diseased spots with other modalities such as radiation and/or radiofrequency/microwave ablation. If you're selected to be in this arm, the type of procedure you receive will vary based on your cancer and what the study doctor recommends for treatment.
Intervention: Consolidative Radiation
Arm A - Participants Who Receive Sequential Procedures
If you are assigned to this arm, study doctors will sequentially remove and treat all visible cancer spots with surgery, radiation, ablation, or other procedures. These interventions might include surgical removal of the diseased part of your lung, liver, lymph nodes, and/or the lining of your belly. In addition, if surgery could not be done, we could treat these diseased spots with other modalities such as radiation and/or radiofrequency/microwave ablation. If you're selected to be in this arm, the type of procedure you receive will vary based on your cancer and what the study doctor recommends for treatment.
Intervention: Ablation Treatment
Arm A - Participants Who Receive Sequential Procedures
If you are assigned to this arm, study doctors will sequentially remove and treat all visible cancer spots with surgery, radiation, ablation, or other procedures. These interventions might include surgical removal of the diseased part of your lung, liver, lymph nodes, and/or the lining of your belly. In addition, if surgery could not be done, we could treat these diseased spots with other modalities such as radiation and/or radiofrequency/microwave ablation. If you're selected to be in this arm, the type of procedure you receive will vary based on your cancer and what the study doctor recommends for treatment.
Intervention: Resection or Excision
Arm A - Participants Who Receive Sequential Procedures
If you are assigned to this arm, study doctors will sequentially remove and treat all visible cancer spots with surgery, radiation, ablation, or other procedures. These interventions might include surgical removal of the diseased part of your lung, liver, lymph nodes, and/or the lining of your belly. In addition, if surgery could not be done, we could treat these diseased spots with other modalities such as radiation and/or radiofrequency/microwave ablation. If you're selected to be in this arm, the type of procedure you receive will vary based on your cancer and what the study doctor recommends for treatment.
Intervention: Peritonectomy
Arm A - Participants Who Receive Sequential Procedures
If you are assigned to this arm, study doctors will sequentially remove and treat all visible cancer spots with surgery, radiation, ablation, or other procedures. These interventions might include surgical removal of the diseased part of your lung, liver, lymph nodes, and/or the lining of your belly. In addition, if surgery could not be done, we could treat these diseased spots with other modalities such as radiation and/or radiofrequency/microwave ablation. If you're selected to be in this arm, the type of procedure you receive will vary based on your cancer and what the study doctor recommends for treatment.
Intervention: Transarterial Radioembolization
Arm B (Control) - Participants Who Receive Standard of Care Chemotherapy
Participants in this arm receive the current standard of care chemotherapy for their specific type of gastrointestinal cancer. This treatment may include the continuation of chemotherapy and a few procedures which may improve your quality of life.
Intervention: Standard of Care Chemotherapy
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: 12 months
The progression free survival (PFS) of participants undergoing sequential procedures (Arm A of study) vs standard of care chemotherapy (participants in Arm B - control group) as assessed by clinical records. Progression free survival will be defined as the time from randomization to first documented disease progression or death as assessed by clinical records.
Secondary Outcomes
- 6 Month Progression Free Survival(6 months)
- Progression Free Survival 2(12 months)
- Median Overall Survival(12 months)
- Financial Toxicity(12 months)
- Post-Procedure Morbidity of Participants in Arm A(12 months)
- The Effect of Interventions on Circulating Tumor DNA (ctDNA)(2 years after randomization)
- 12 Month Progression Free Survival(12 months)
- Health-Related Quality of Life(12 months)
- Post-Procedure Mortality of Participants in Arm A(12 months)
- Incidence of Adverse Events Reported Among Participants in Arm B (Standard of Care Group)(12 months)
- Circulating Tumor DNA (ctDNA) Progression Free survival(2 years after randomization)