Study Comparing Standard of Care Chemotherapy With/ Without Sequential Cytoreductive Surgery for Patients With Metastatic Foregut Cancer and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid Levels

NCT04931420 | Withdrawn Phase 2

• 1 other identifier: IRB20-2185
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Cancer; Foregut Carcinoid Tumor; Gastric Adenocarcinoma; Gallbladder Adenocarcinoma; Liver Cancer; GI Cancer; GI Carcinoma; Lung Cancer

Keywords

metastatic cancer; foregut cancer; metastatic foregut cancer; gastrointestinal cancer; GI cancer; cytoreductive surgery; cytoreductive treatment

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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.

  12 months

Secondary Outcomes (11)

• 6 Month Progression Free Survival

  6 months

• Progression Free Survival 2

  12 months

• 12 Month Progression Free Survival

  12 months

• Median Overall Survival

  12 months

• Health-Related Quality of Life

  12 months

Study Arms (2)

Arm A - Participants Who Receive Sequential Procedures

EXPERIMENTAL

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.

Procedure: Video-Assisted Thoracic Surgery (VATS); Procedure: Lobectomy; Radiation: Consolidative Radiation; Radiation: Ablation Treatment; Procedure: Resection or Excision; Procedure: Peritonectomy; Other: Transarterial Radioembolization

Arm B (Control) - Participants Who Receive Standard of Care Chemotherapy

OTHER

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.

Drug: Standard of Care Chemotherapy

Interventions

Standard of Care Chemotherapy DRUG

* 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.

Arm B (Control) - Participants Who Receive Standard of Care Chemotherapy

Video-Assisted Thoracic Surgery (VATS) PROCEDURE

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.

Also known as: thoracoscopy, thoracoscopic surgery or pleuroscopy,

Arm A - Participants Who Receive Sequential Procedures

Lobectomy PROCEDURE

If you have lung cancer, you may receive a lobectomy: A major/invasive surgical procedure where an entire lobe of your lung is removed.

Arm A - Participants Who Receive Sequential Procedures

Consolidative Radiation 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.

Also known as: intensification therapy, postremission therapy.

Arm A - Participants Who Receive Sequential Procedures

Ablation Treatment RADIATION

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.

Arm A - Participants Who Receive Sequential Procedures

Resection or Excision PROCEDURE

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.

Arm A - Participants Who Receive Sequential Procedures

Peritonectomy PROCEDURE

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.

Arm A - Participants Who Receive Sequential Procedures

Transarterial Radioembolization OTHER

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.

Also known as: TARE

Arm A - Participants Who Receive Sequential Procedures

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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 5 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 (Appendix 4); all screening laboratory tests should be performed within 30 days prior to the first study intervention.
• Prior Therapy
• 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
• 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.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status score 0-1 at the time of randomization.

Sponsors & Collaborators

• University of Chicago: lead

MeSH Terms

Conditions

Neoplasm Metastasis; Liver Neoplasms; Gastrointestinal Neoplasms; Lung Neoplasms

Interventions

Thoracic Surgery, Video-Assisted; Thoracoscopy; Anterior Temporal Lobectomy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Video-Assisted Surgery; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Thoracic Surgical Procedures; Neurosurgical Procedures

Study Officials

• Kiran Turaga, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 18, 2021
• Study Start: May 19, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share