Metastatic Cancer, Foregut Carcinoid Tumor, Gastric Adenocarcinoma, Gallbladder Adenocarcinoma, Liver Cancer, GI Cancer, GI Carcinoma, Lung Cancer
Conditions
Keywords
metastatic cancer, foregut cancer, metastatic foregut cancer, gastrointestinal cancer, GI cancer, cytoreductive surgery, cytoreductive treatment
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.
Interventions
* If you have cancer of the stomach or food pipe (esophagus): the preferred chemotherapy regimen includes two or three medications. These drugs include Cisplatin or Oxaliplatin and 5-fluorouracil (5 FU) in combination with Docetaxel. * If you have cancer of the pancreas or ampulla: the preferred chemotherapy medicines include Gemcitabine or a three-drug combination chemotherapy called FOLFIRINOX, which includes 5FU, Leucovorin, Irinotecan, and Oxaliplatin. * If you have bile duct cancers: a combination of Gemcitabine, platinum agents, or fluoropyrimidine will be considered.
PROCEDUREVideo-Assisted Thoracic Surgery (VATS)
If you have lung cancer, you may receive video-assisted thoracic surgery (VATS): a type of minimally invasive thoracic surgery of the chest, performed with a thoracoscope (small videoscope) using small incisions and special instruments to minimize trauma.
PROCEDURELobectomy
If you have lung cancer, you may receive a lobectomy: A major/invasive surgical procedure where an entire lobe of your lung is removed.
RADIATIONConsolidative Radiation
A type of radiation treatment used to kill any cancer cells that may be left in the body. It may also include a stem cell transplant or treatment with drugs that kill cancer cells.
RADIATIONAblation Treatment
Depending on the location of you cancer and the state of your cancer after chemotherapy, you may receive on the the following ablation treatments: -Microwave or Radiofrequency Ablation: Radiofrequency ablation (RFA) and microwave ablation (MWA) are treatments that remove liver tumors by placing a needle through the skin into the tumor. In RFA, high-frequency electrical currents are passed through an electrode in the needle, creating a small region of heat. In MWA, microwaves are created from the needle to create a small region of heat. The heat destroys the liver cancer cells. -General Tumor Ablation Treatment: a minimally invasive surgical method to treat solid cancers. Special probes are used to burn or freeze cancers without the usual surgery. Doctors use images of your tumor to guide where they place the needle. This requires only a tiny hole, usually less than 3 mm via which the probe is introduced.
PROCEDUREResection or Excision
Depending on the type of GI cancer you have and the state of your cancer after chemotherapy, you may receive a resection or excision: a surgical procedure that focuses on removing all or part of a tumor/organ/body using a sharp knife (scalpel) or other cutting instrument.
PROCEDUREPeritonectomy
Peritonectomy is a surgery used to remove peritoneal tumors (tumors in the lining of the abdomen/stomach) from a patient. Following surgery, a heated chemotherapy bath (HIPEC) is commonly administered.
If you have cancer in your biliary tract (gallbladder, pancreas or liver), you may receive transarterial radioembolization known as TARE. TARE allows doctors to deliver radiation treatment directly to the liver using a minimally invasive technique that is designed to cause few side effects. TARE allows doctors to thread a catheter through a small incision in the participant's upper thigh through the artery that goes directly to the liver.
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
A participant will be eligible for inclusion in the study if the participant: 1. 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. 1. All participants must have confirmed histologic diagnosis of the primary tumor 2. Excludes patients with bone and brain metastasis (See
Exclusion criteria
) 2. 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). 3. 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: 1. Up to 5 pulmonary metastasis amenable to wedge resection (maximum of 3 wedge resections) or lobectomy (single lobectomy) or consolidative radiation/ablative therapy 2. 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). 3. Lymphatic metastases that are resectable or intervenable (limited to only two non-regional sites). 4. Resectable peritoneal disease with a PCI of \<6 and the ability to obtain a CC0 cytoreduction. 5. Distant metastasis must be limited to two of the above-mentioned sites (a-d). 6. If both pulmonary and liver metastasis are present (a, b), then a total of 5 lesions will be considered oligometastatic. 4. 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. 5. Has adequate organ function, as described below (Appendix 4); all screening laboratory tests should be performed within 30 days prior to the first study intervention. Prior Therapy 6. Patients taking substrates, inhibitors, or inducers of Cytochrome P450 3A4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions. Demographics 7. Is male or female, 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. 8. Has an Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 at the time of randomization. Male Participants 9. 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. Female Participants 10. 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) for at least 95 days following completion, corresponding to time needed to eliminate any study intervention(s). 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 11. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for Future Biomedical Research (FBR). However, the participant may participate in the main study without participating in FBR.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival 2 | 12 months | The percentage of participants in each arm without disease progression/death from randomization to progression on second line therapy, which includes repeat interventions. |
| 12 Month Progression Free Survival | 12 months | The percentage of participants in each arm without disease progression/death at 12 months as assessed by clinical records. |
| Median Overall Survival | 12 months | The median overall survival of participants undergoing sequential procedures (Arm A) vs standard of care therapy (Arm B) as assessed by clinical records. Median overall survival will be defined as the time from randomization to death from any cause. |
| Health-Related Quality of Life | 12 months | Health-related quality of life (HRQoL) for participants undergoing sequential procedures (Arm A) vs. the HRQoL for participants receiving standard of care treatment (Arm B). This will be assessed by quality of questionnaires completed by participants at baseline and after treatment. |
| Financial Toxicity | 12 months | The financial burden and its consequences faced by participants undergoing sequential procedures vs. the financial burden experienced by participants receiving standard of care treatment (Arm B). This financial burden/toxicity will be assessed by the Comprehensive Score for Financial Toxicity (COST) questionnaire, a standardized participant-friendly questionnaire used to measure financial toxicity/burden of treatment. |
| 6 Month Progression Free Survival | 6 months | The percentage of participants in each arm without disease progression/death at 6 months as assessed by clinical records. |
| Post-Procedure Mortality of Participants in Arm A | 12 months | The mortality (the number of deaths) of participants after undergoing sequential cytoreductive procedures (procedures used to remove tumors) as assessed by clinical records. |
| Incidence of Adverse Events Reported Among Participants in Arm B (Standard of Care Group) | 12 months | The safety/ tolerability of standard of care treatment as assessed by reported adverse events from participants in Arm B. Adverse Events will be measured using the Common Terminology Criteria for Adverse Events (CTCAE) v.5. |
| Circulating Tumor DNA (ctDNA) Progression Free survival | 2 years after randomization | The median circulating tumor DNA (ctDNA) progression free survival, which will be defined as the time from randomization to first documented disease progression, positive ctDNA detection, or death as assessed by the radiology team in participants with undetectable ctDNA. ctDNA levels in participants will be tested/assessed using liquid biopsies. |
| The Effect of Interventions on Circulating Tumor DNA (ctDNA) | 2 years after randomization | The effect of interventions on circulating tumor DNA (ctDNA) levels in participants who receive aggressive interventions (Arm A) versus standard of care treatments (Arm B). The effect of interventions on ctDNA will be assessed based on recorded ctDNA levels measured using liquid biopsies at baseline and after treatment. |
| Post-Procedure Morbidity of Participants in Arm A | 12 months | The morbidity (the state of having a particular illness) of participants after undergoing sequential cytoreductive procedures (procedures used to remove tumors) as assessed by clinical records. |
Outcome results
None listed