WITHDRAWN

A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies

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Conditions

Gastrointestinal CarcinomaPancreatic CancerHepatocellular CancerCholangiocarcinomaDuodenal CancerColorectal CancerSmall Bowel CancerMetastatic CancersKRAS MutationsCell TherapyGene TherapyTp53 MutationsImmunotherapyKRAS G12DKRAS G12VTp53R175H

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: Gastrointestinal (GI) cancer affects the organs (such as the stomach, large and small intestine, pancreas, colon, liver, and biliary system) of the digestive tract. In some participants who have had surgery for GI cancer, blood tests show that the cancer has spread despite being unable to be identified by scans. Certain gene mutations (changes) in GI cancer (such as KRAS or TP53) can be targeted by T cells, a type of immune cell, in individuals with specific HLA types (genes that help proteins in the body know what is self and non-self). Researchers want to see if they can stop GI cancer from returning or spreading in people with these gene mutations and specific HLA types. Objective: To test therapy with modified T-cells to prevent or delay the return of GI cancer after standard treatment. T-cells play a role in the body s immune system. Eligibility: People aged 18 to 72 years with GI cancer that was treated with standard therapy and is not seen on imaging scans. They must have specific gene mutations and HLA types. They also must have certain clinical or blood tests showing the cancer is spreading (elevating CA19-9 or detectable ctDNA). Design: Participants will be divided into 2 groups. Participants nor the study team can choose what Group to participate in; this is done by randomization , like flipping a coin. Participants will have a 1-to-1 chance of being in Group 1 or Group 2. Group 1 will receive T-cell therapy. Their own T-cells will be collected. In a lab, the cells will be combined with a virus that carries a protein to target cancer cells. Group 1 participants will stay in the hospital for 3 weeks or more. They will have chemotherapy, and their modified T-cells will be infused through a tube attached to a needle inserted into a vein. Group 1 participants will visit the clinic every 3 months for 1 year and then every 6 months for 5 years. Then they will have follow-up visits for another 10 years under a different protocol. Group 2 participants will not receive treatment with T-cells. They will visit the clinic every 3 months for 1 year and then every 6 months for 5 years.

Official Title

A Phase II Study of Adjuvant Immunotherapy Targeting KRAS G12D, KRAS G12V, or TP53 R175H for Participants With Advanced Gastrointestinal Malignancies

Quick Facts

Study Start:2025-09-09
Study Completion:2025-09-09
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:WITHDRAWN

Study ID

NCT06690281

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 72 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Resected pancreas ductal adenocarcinoma (PDAC):
  2. * Resected pancreas ductal adenocarcinoma
  3. * If stage I-III has a history of detectable circulating tumor DNA (ctDNA) after resection/local treatment of all known disease.
  4. * Had metastatic disease (stage IV) at diagnosis and were down staged with chemotherapy and underwent resection.
  5. * Participants with stage IV colorectal cancer with metastases to the liver, lung, and/or lymph nodes that were completely treated with local therapy (resection, ablation, and/or radiotherapy).
  6. * Must have a history of detectable ctDNA after resection/local treatment of all known disease.
  7. * Participants with resected gastroesophageal cancer, hepatocellular cancer, cholangiocarcinoma, duodenal, small bowel, or primary colorectal cancer (i.e., pathologic stage I-III as distinguished from CRLM).
  8. * Must have a history of detectable ctDNA after resection/local treatment of all known disease.
  9. * Confirmation of diagnosis of cancer by the NCI Laboratory of Pathology (LP).
  10. * Must have a history of:
  11. * KRAS G12D mutation plus HLA-A\*11:01
  12. * TP53 R175H mutation plus HLA-A\*02:01.
  13. * Participants with PDAC should receive neoadjuvant or adjuvant chemotherapy (5-FU or gemcitabine-based).
  14. * Participants with CRLM should have received at least one line of 5FU-based chemotherapy (i.e., FOLFOX or FOLFIRI).
  15. * Participants with resected stage III colon cancer should have received 5FU-based adjuvant therapy (i.e., FOLFOX or FOLFIRI).
  16. * CRLM only: Participants with a history of brain metastases that have been treated with stereotactic radiosurgery or resection must be clinically stable for 3 months after treatment to be eligible.
  17. * Age \>= 18 years and \<= 72 years.
  18. * Clinical performance status of ECOG 0 or 1
  19. * Individuals of child-bearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD\], abstinence, surgical sterilization) at the study entry and up to and 12 months after the last dose of combined chemotherapy. Individuals that can father children must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drugs. We also will recommend individuals that can father children with partners that can bear children ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Individuals that can father
  20. * Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 4 months after the last dose of the study drug(s).
  21. * Viral testing
  22. * Seronegative for human immunodeficiency virus (HIV) antibody.
  23. * Negative for hepatitis B (HBV) surface antigen (HbsAg), and seronegative for hepatitis C (HCV) antibody. If the HCV antibody test is positive, then the participant must be tested for the presence of antigen by RT-PCR and be HCV RNA negative to be eligible.
  24. * Hematology
  25. * Absolute neutrophil count (ANC) \> 1000/mm\^3 without the support of filgrastim
  26. * White blood cells (WBC) \>= 2500/mm\^3
  27. * Platelet count \>= 80,000/mm\^3
  28. * Hemoglobin \> 8.0 g/dL.
  29. * Chemistry
  30. * Alanine aminotransferase (ALT) \<= 5.0 x upper limit of normal (ULN)
  31. * Aspartate aminotransferase (AST) \<= 5.0 x ULN
  32. * Creatinine \<= 1.6 mg/dL
  33. * Total bilirubin \<= 2.0 mg/dL, except in participants with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL.
  34. * Four weeks must have passed after any prior systemic therapy for cancer, any investigational agents, surgical procedures, or limited field radiotherapy prior to randomization, as long as related major organ toxicities have recovered to grade 1 or less per Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.
  35. * Ability of the participant to understand and the willingness to sign a written informed consent document.
  36. * Willing to sign a durable power of attorney.
  37. * Participants must be co-enrolled on protocols 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols), and 09-C-0161 (Follow-up Protocol for Subjects Previously Enrolled on NCI Surgery Branch Studies).
  1. * Unequivocal radiographic evidence of residual tumor.
  2. * Participants with measurable disease per RECIST v1.1 criteria.
  3. * Any form of secondary immunosuppression.
  4. * Active or chronic infections requiring anti-microbial, anti-fungal, or anti-viral treatment.
  5. * Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and Acquired immunodeficiency syndrome \[AIDS\]).
  6. * History of major organ autoimmune disease.
  7. * History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
  8. * History of coronary revascularization or ischemic symptoms.
  9. * Left ventricular ejection fraction (LVEF) \<= 45% for participants with a clinical history prompting cardiac evaluation (e.g., participants who are \>= 65 years of age, or who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias, including but not limited to atrial fibrillation, ventricular tachycardia, heart block OR Participants \< 65 years of age with cardiac risk factors \[e.g., diabetes, hypertension, obesity\]).
  10. * Forced expiratory volume in the first second (FEV1) \<= 50% predicted for participants with a clinical history prompting pulmonary evaluation (e.g., a prolonged history of cigarette smoking \[\>= 20 pack-year smoking history within the past two years\], symptoms
  11. * Positive beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in IOCBP at screening.
  12. * Uncontrolled intercurrent illness evaluated by medical history and physical exam that are not stable and would potentially increase the risk to the participant.

Contacts and Locations

Principal Investigator

Nicholas D Klemen, M.D.
PRINCIPAL_INVESTIGATOR
National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Nicholas D Klemen, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-09-09
Study Completion Date2025-09-09

Study Record Updates

Study Start Date2025-09-09
Study Completion Date2025-09-09

Terms related to this study

Keywords Provided by Researchers

  • KRAS Mutations
  • Cell Therapy
  • Gene Therapy
  • Tp53 Mutations
  • Immunotherapy
  • KRAS G12D
  • KRAS G12V
  • Tp53
  • R175H

Additional Relevant MeSH Terms

  • Gastrointestinal Carcinoma
  • Pancreatic Cancer
  • Hepatocellular Cancer
  • Cholangiocarcinoma
  • Duodenal Cancer
  • Colorectal Cancer
  • Small Bowel Cancer
  • Metastatic Cancers