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Metastatic CancerPhase 2NCT04931420

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

A Phase 2 study testing Video-Assisted Thoracic Surgery (VATS), Lobectomy and Consolidative Radiation in people with Metastatic Cancer and Foregut Carcinoid Tumor, run by University of Chicago.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
Video-Assisted Thoracic Surgery (VATS), Lobectomy and Consolidative Radiation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
19 May 2022to 1 Nov 2027
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Male Participants
  • 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
  • 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
  • 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.

Who cannot join

  • 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.
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  • 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.
  • Has poorly controlled hypertension defined as SBP ≥150mmHg and/or DBP ≥90mmHg.
  • Has moderate to severe hepatic impairment (Child-Pugh B or C).
  • Has a known psychiatric condition such as schizophrenia, mania, delirium, or a substance abuse disorder that would interfere with the study-related procedures.
  • Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (severe dysphasia, bowel obstruction, malabsorption).
  • Has known malignant pleural effusion or previous malignant effusion previously treated at the time of enrollment.
  • Has histologic subtypes not included in the inclusion criteria (including esophageal squamous cell carcinoma, gastroenteropancreatic neuroendocrine tumors, hepatocellular carcinoma, etc.).
  • Has ECOG performance status score 2 or greater.
  • Has a primary tumor that is not amenable to treatment.
  • Has weight loss ≥ 20% from diagnosis despite appropriate nutritional support.
  • Has progressive disease following the first three months of chemotherapy.
  • Patients with detectable circulating tumor DNA (ctDNA) following three months of induction chemotherapy.
  • Prior/Concomitant Therapy
  • Has previously treated metastatic disease with surgery, radiation, or ablative procedures.
  • 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.
  • 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.
  • 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
  • Has an active infection requiring systemic therapy
  • Has known active TB/ COVID infection
  • 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
  • Has a known history of HIV infection
  • 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
  • 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.
  • Inability to receive chemotherapy and/or surgery and/or radiotherapy and/or ablative procedures due to medical/insurance reasons.
  • Has peritoneal metastases with a peritoneal carcinoma index (PCI) score of >6.
  • Requires emergency surgery due to bleeding, perforation, or obstruction.

About this study

Official title: 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

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.

Read the 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.

Being tested
Standard of Care Chemotherapy, Video-Assisted Thoracic Surgery (VATS), Lobectomy, Consolidative Radiation, Ablation Treatment
Keywords
metastatic cancer, foregut cancer, metastatic foregut cancer, gastrointestinal cancer, GI cancer, cytoreductive surgery, cytoreductive treatment
Medical subject headings
Neoplasm Metastasis, Liver Neoplasms, Gastrointestinal Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard of Care ChemotherapyDrug

    • 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.

  • Video-Assisted Thoracic Surgery (VATS)Procedure or surgery

    Also called thoracoscopy, thoracoscopic surgery or pleuroscopy,

    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.

  • LobectomyProcedure or surgery

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

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

  • Consolidative RadiationRadiation

    Also called intensification therapy, postremission therapy.

    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.

  • Ablation TreatmentRadiation

    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.

  • Resection or ExcisionProcedure or surgery

    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.

  • PeritonectomyProcedure or surgery

    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.

  • Transarterial RadioembolizationOther

    Also called TARE

    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.

Study groups in NCT04931420
Study groupRoleWhat they receive
Arm A - Participants Who Receive Sequential ProceduresExperimentalIf 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.
Receives: 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 ChemotherapyOtherParticipants 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.
Receives: Drug: Standard of Care Chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 months

Secondary outcomes (11)

  1. 6 Month Progression Free Survival

    The percentage of participants in each arm without disease progression/death at 6 months as assessed by clinical records.

    Measured: 6 months

  2. Progression Free Survival 2

    The percentage of participants in each arm without disease progression/death from randomization to progression on second line therapy, which includes repeat interventions.

    Measured: 12 months

  3. 12 Month Progression Free Survival

    The percentage of participants in each arm without disease progression/death at 12 months as assessed by clinical records.

    Measured: 12 months

  4. Median Overall Survival

    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.

    Measured: 12 months

  5. Health-Related Quality of Life

    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.

    Measured: 12 months

  6. Financial Toxicity

    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.

    Measured: 12 months

  7. Post-Procedure Morbidity of Participants in Arm A

    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.

    Measured: 12 months

  8. Post-Procedure Mortality of Participants in Arm A

    The mortality (the number of deaths) of participants after undergoing sequential cytoreductive procedures (procedures used to remove tumors) as assessed by clinical records.

    Measured: 12 months

  9. Incidence of Adverse Events Reported Among Participants in Arm B (Standard of Care Group)

    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.

    Measured: 12 months

  10. Circulating Tumor DNA (ctDNA) Progression Free survival

    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.

    Measured: 2 years after randomization

  11. The Effect of Interventions on Circulating Tumor DNA (ctDNA)

    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.

    Measured: 2 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2021
  2. Study start19 May 2022
  3. Primary completion1 May 2026 (estimated)
  4. Study completion1 Nov 2027 (estimated)

Why it stopped: PI left site

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04931420
Sponsor's protocol ID
IRB20-2185
Status last verified
Jul 2024
First submitted
8 Jun 2021
Last updated
31 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Video-Assisted Thoracic Surgery (VATS), Lobectomy and Consolidative Radiation in people with Metastatic Cancer and Foregut Carcinoid Tumor, run by University of Chicago.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 31 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04931420.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2024.

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