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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04931420
Recruitment Status : Not yet recruiting
First Posted : June 18, 2021
Last Update Posted : November 5, 2021
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Tracking Information
First Submitted Date  ICMJE June 8, 2021
First Posted Date  ICMJE June 18, 2021
Last Update Posted Date November 5, 2021
Estimated Study Start Date  ICMJE December 1, 2021
Estimated Primary Completion Date May 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2021)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
Median Progression Free Survival [ Time Frame: 12 months ]
The median progression free survival (PFS) of participants undergoing sequential procedures (Arm A of study) vs standard of care treatment (participants in Arm B of study - aka the control group) as assessed by clinical records. Median progression free survival will be defined as the time from randomization to first documented disease progression (first measurement at clinical progression or 3 months after randomization) or death.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2021)
  • 6 Month Progression Free Survival [ Time Frame: 6 months ]
    The percentage of participants in each arm without disease progression/death at 6 months as assessed by clinical records.
  • Progression Free Survival 2 [ Time Frame: 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 [ Time Frame: 12 months ]
    The percentage of participants in each arm without disease progression/death at 12 months as assessed by clinical records.
  • Median Overall Survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Post-Procedure Morbidity of Participants in Arm A [ Time Frame: 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.
  • Post-Procedure Mortality of Participants in Arm A [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
  • 6 Month Progression Free Survival [ Time Frame: 6 months ]
    The percentage of participants in each arm without disease progression/death at 6 months as assessed by clinical records.
  • 12 Month Progression Free Survival [ Time Frame: 12 months ]
    The percentage of participants in each arm without disease progression/death at 12 months as assessed by clinical records.
  • Median Overall Survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • Post-Procedure Morbidity of Participants in Arm A [ Time Frame: 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.
  • Post-Procedure Mortality of Participants in Arm A [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Cancer
  • Foregut Carcinoid Tumor
  • Gastric Adenocarcinoma
  • Gallbladder Adenocarcinoma
  • Liver Cancer
  • GI Cancer
  • GI Carcinoma
  • Lung Cancer
Intervention  ICMJE
  • Drug: Standard of Care Chemotherapy
    • 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.
  • Procedure: Video-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.
    Other Name: thoracoscopy, thoracoscopic surgery or pleuroscopy,
  • Procedure: Lobectomy

    If you have lung cancer, you may receive a lobectomy:

    A major/invasive surgical procedure where an entire lobe of your lung is removed.

  • Radiation: Consolidative 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.
    Other Name: intensification therapy, postremission therapy.
  • Radiation: Ablation 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.

  • Procedure: Resection 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.
  • Procedure: Peritonectomy
    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.
  • Other: Transarterial Radioembolization

    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.

    Other Name: TARE
Study Arms  ICMJE
  • Experimental: 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.

    Interventions:
    • 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
    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: Drug: Standard of Care Chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2021)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 1, 2025
Estimated Primary Completion Date May 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Exclusion Criteria:

The participant must be excluded from the study if the participant:

Medical Conditions

  1. 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.

  2. Has hypoxia as defined by pulse oximeter reading <92% at rest or requires intermittent or chronic supplemental oxygen.
  3. 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.

  4. Has known central nervous system (CNS) metastasis and/or carcinomatous meningitis.
  5. Has known osseous metastasis.
  6. 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.
  7. Has poorly controlled hypertension defined as SBP ≥150mmHg and/or DBP ≥90mmHg.
  8. Has moderate to severe hepatic impairment (Child-Pugh B or C).
  9. Has a known psychiatric condition such as schizophrenia, mania, delirium, or a substance abuse disorder that would interfere with the study-related procedures.
  10. Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (severe dysphasia, bowel obstruction, malabsorption).
  11. Has known malignant pleural effusion or previous malignant effusion previously treated at the time of enrollment.
  12. Has histologic subtypes not included in the inclusion criteria (including esophageal squamous cell carcinoma, gastroenteropancreatic neuroendocrine tumors, hepatocellular carcinoma, etc.).
  13. Has ECOG performance status score 2 or greater.
  14. Has a primary tumor that is not amenable to treatment.
  15. Has weight loss ≥ 20% from diagnosis despite appropriate nutritional support.
  16. Has progressive disease following the first three months of chemotherapy.
  17. Patients with detectable circulating tumor DNA (ctDNA) following three months of induction chemotherapy.

    Prior/Concomitant Therapy

  18. Has previously treated metastatic disease with surgery, radiation, or ablative procedures.

    a. Patients can be enrolled if they have received systemic chemotherapy consistent with the trial protocol, and they meet all of the inclusion criteria and none of the remaining exclusion criteria.

  19. Has had major surgery within 3 weeks prior to the first dose of the study intervention. Participants must have recovered from all surgery-related complications.
  20. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include but are not limited to the following: measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccine for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccine (eg. FluMist®) are live attenuated vaccines and are not allowed.

    Diagnostic Assessments

  21. Has an active infection requiring systemic therapy
  22. Has known active TB/ COVID infection
  23. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study intervention
  24. Has a known history of HIV infection
  25. Has a known history of HBV (defined as HBsAg reactive) or known active HCV (defined as HCV RNA [qualitative] is detected) infection.

    Note: Testing for HBV and HCV is only required if mandated by the local health authority.

    Other Exclusions

  26. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 95 days after the last study intervention.
  27. Inability to receive chemotherapy and/or surgery and/or radiotherapy and/or ablative procedures due to medical/insurance reasons.
  28. Has peritoneal metastases with a peritoneal carcinoma index (PCI) score of >6.
  29. Requires emergency surgery due to bleeding, perforation, or obstruction.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Kiran Turanga, MD 773-702-6771 PhaseIICRA@medicine.bsd.uchicago.edu
Contact: Daniel Catenacci, MD 773-702-7596 dcatenac@bsd.uchicago.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04931420
Other Study ID Numbers  ICMJE IRB20-2185
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party University of Chicago
Study Sponsor  ICMJE University of Chicago
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kiran Turanga, MD University of Chicago
PRS Account University of Chicago
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP