Immunoterapi (Toripalimab) for å forhindre gjentakelse etter operasjon for feilpasningsreparasjonsmangel IIB, IIC eller III tykktarmskreft
En fase II -studie av adjuvans Toripalimab i høyrisiko lokalisert tykktarmskreft med feilpasningsreparasjonsmangel
This phase II trial tests how well immunotherapy (toripalimab) works for reducing the risk of cancer recurrence after surgery in patients with mismatch repair deficient stage IIB, IIC, or III colon cancer.
Studieoversikt
Status
Forhold
Detaljert beskrivelse
PRIMARY OBJECTIVE:
I. Evaluate the efficacy of adjuvant toripalimab in patients with resected stage IIB, IIC, and III mismatch repair deficient (dMMR) colon cancer by measuring 3-year disease-free survival.
SECONDARY OBJECTIVES:
I. Define the immune related toxicity profile of toripalimab in the adjuvant setting.
II. Further evaluate the efficacy of adjuvant toripalimab specifically by measuring 3-year relapse free survival (RFS), 5-year disease free survival (DFS), and 5-year overall survival.
TERTIARY/EXPLORATORY OBJECTIVES:
I. To explore immune, ctDNA, and omic markers associated with clinical efficacy (DFS).
II. To assess patient reported outcomes (PRO) and health related quality of life (QoL).
OUTLINE:
Eligible consenting participants will receive toripalimab intravenously every 3 weeks for 6 months (8 doses) in the absence of disease recurrence or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months until 5 years post-resection. After completion of study medication, participants undergo surveillance follow up with blood tests, computed tomography (CT) scans, colonoscopy at specified intervals until 5 years post-resection. Patient reported outcomes and quality of life will also be assessed with questionnaires.
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiekontakt
- Navn: Oluwadunni E. Emiloju, MBBS, MS
- Telefonnummer: 404-778-1900
- E-post: oluwadunni.eunice.emiloju@emory.edu
Studer Kontakt Backup
- Navn: Olatunji B. Alese, MD, FASCO
- E-post: olatunji.alese@emory.edu
Studiesteder
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Rekruttering
- Emory University Hospital/Winship Cancer Institute
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Hovedetterforsker:
- Oluwadunni E. Emiloju, MBBS, MS
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Ta kontakt med:
- Tyler Whitfield
- Telefonnummer: 404-778-1900
- E-post: tyler.stephen.whitfield@emory.edu
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Atlanta, Georgia, Forente stater, 30308
- Rekruttering
- Emory University Hospital Midtown
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Ta kontakt med:
- Jalpa Patel
- E-post: jalpa.r.patel@emory.edu
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Hovedetterforsker:
- Oluwadunni E. Emiloju, MBBS, MS
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Atlanta, Georgia, Forente stater, 30342
- Rekruttering
- Emory Saint Joseph's Hospital
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Hovedetterforsker:
- Oluwadunni E. Emiloju, MBBS, MS
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Ta kontakt med:
- Ainsley Hymel
- E-post: ainsley.hymel@emory.edu
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Atlanta, Georgia, Forente stater, 30033
- Rekruttering
- Emory Decatur Hospital
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Hovedetterforsker:
- Oluwadunni Emiloju
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Ta kontakt med:
- Kathleen Coleman
- Telefonnummer: 404-778-1900
- E-post: kmcole5@emory.edu
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Johns Creek, Georgia, Forente stater, 30097
- Rekruttering
- Emory Johns Creek Hospital
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Hovedetterforsker:
- Oluwadunni E. Emiloju, MBBS, MS
-
Ta kontakt med:
- Hafsa Ahmed
- E-post: hafsa.maheen.ahmed@emory.edu
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
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Patients with resected pathologic stage IIB, IIC and III dMMR colon cancer (American Joint Committee on Cancer [AJCC] 8)
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Deficient mismatch repair (MMR) by immunohistochemistry or microsatellite instability (MSI-H) by polymerase chain reaction (PCR) or next generation sequencing (NGS)
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Complete (R0) resection of pathologic stage IIB, IIC and III dMMR colon cancer 4 to 12 weeks prior to first dose of study drug
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Available tissue sample from surgical specimen
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Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
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Absolute neutrophil count (ANC) ≥ 1,000 /mcL
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Platelets ≥ 75,000 / mcL
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Hemoglobin ≥ 9 g/dL or ≥ 5.0 mmol/L
- Transfusion is allowed to obtain an adequate hemoglobin level
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Creatinine ≤ 1.5 x upper limit of normal (ULN) or measured or calculated creatinine clearance ≥ 40 mL/min for patient with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl])
- Creatinine clearance should be calculated per institutional standard
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Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN
- Patients with previously diagnosed Gilbert syndrome can have total bilirubin < 3.0 mg/dL
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Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x ULN
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Alkaline phosphatase ≤ 3 x ULN
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Signed informed consent
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Patients at least 18 years of age
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Colonoscopy should be performed before surgery and if synchronous colon cancers are present, both must have deficient MMR and both must have undergone complete resection for patient to be eligible. If colonoscopy was not done pre-operatively, the patient may still be eligible if all other inclusion criteria are met. It should however be performed within 6 months after initial colon resection surgery
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Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. WOCBP are women younger than 55 years (yrs) of age excluding those who are surgically unable to get pregnant due to prior hysterectomy and or bilateral salpingo-oophorectomy
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Patients of childbearing / reproductive potential should use adequate birth control methods, as defined by the investigator, during the study treatment period and for a period of 90 days after the last dose of study drug. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard
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Female patients who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 90 days after the last dose of study drug
Exclusion Criteria:
- Neoadjuvant treatment for dMMR colon cancer
- Presence of metastatic dMMR colon cancer
- Underlying medical conditions that, in the investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of adverse events
- Uncontrolled psychiatric illness or psychological condition potentially hampering compliance with the study protocol and follow-up schedule
- History of pneumonitis requiring treatment with steroids, or history of interstitial lung disease
- History of prior malignancy other than the cancer under study, that is progressing or has required active treatment within the past 3 years. Exceptions include adequately treated basal cell or squamous cell carcinoma of skin, superficial bladder cancer, in situ cervical cancer, in situ breast cancer, other in situ cancers, prostate cancer with a Gleason score ≤6 that does not need therapy or other local tumors that are considered cured.
- Autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with vitiligo, diabetes mellitus type 1, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, controlled psoriasis or resolved childhood asthma/atopy not requiring systemic treatment can be enrolled
- Active hepatitis B or hepatitis C
- Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
- Treatment with live vaccines within 30 days prior to the first dose of study medication. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, nasal seasonal flu, H1N1 flu, rabies, Bacille Calmette Guerin (BCG) and typhoid vaccine
- Prior treatment with any immune checkpoint inhibitor
- Current pregnancy or breastfeeding
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Treatment (toripalimab)
Eligible consenting participants receive toripalimab intravenously every 3 weeks for 6 months (8 doses) in the absence of disease recurrence or unacceptable toxicity. Following this, patients undergo surveillance follow up with blood tests, computed tomography (CT) scans, colonoscopy at specified intervals until 5 years post-resection. For patients who have a recurrence, a biopsy will be performed at the time of recurrence. |
Undergo CT
Andre navn:
Ancillary studies Undergo biopsy
Andre navn:
Undergo collection of blood samples
Andre navn:
Undergo colonoscopy Given IV
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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3-year Disease free survival (DFS)
Tidsramme: Time between the date of registration and the first date of documented recurrence or death due to any cause assessed up to 3 years
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Time between the date of registration and the first date of documented recurrence, regardless of discontinuation of study drug, or death due to any cause, assessed at 3 years |
Time between the date of registration and the first date of documented recurrence or death due to any cause assessed up to 3 years
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Incidence of treatment-related adverse events
Tidsramme: Up to 5 years
|
Safety will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Treatment-related adverse events (defined as potentially, probably and definitely) will be summarized in preferred term by system organ class and listed on an individual subject basis at patient level. Immune-related adverse events will also be tabulated. |
Up to 5 years
|
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3-year Relapse free survival (RFS)
Tidsramme: Time between the date of registration and the first date of documented disease recurrence assessed up to 3 years.
|
Time between the date of registration and the first date of documented disease recurrence, assessed at 3 years |
Time between the date of registration and the first date of documented disease recurrence assessed up to 3 years.
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5-year DFS
Tidsramme: Time between the date of registration and the first date of documented recurrence, or death due to any cause assessed up to 5 years
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Time between the date of registration and the first date of documented recurrence, regardless of discontinuation of study drug, or death due to any cause, assessed at 5 years. |
Time between the date of registration and the first date of documented recurrence, or death due to any cause assessed up to 5 years
|
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Colon cancer specific survival (CCSC)
Tidsramme: Time between the date of registration and the date of death due to colon cancer, assessed up to 5 years
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CCSC is the time between the date of registration and the date of death due to colon cancer, assessed up to 5 years |
Time between the date of registration and the date of death due to colon cancer, assessed up to 5 years
|
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Overall survival (OS)
Tidsramme: Time between the date of registration and the date of death due to any cause, assessed up to 5 years
|
Time between the date of registration and the date of death due to any cause. |
Time between the date of registration and the date of death due to any cause, assessed up to 5 years
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Oluwadunni E. Emiloju, MBBS, MS, Emory University Hospital/Winship Cancer Institute
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Neoplasmer etter nettsted
- Neoplasmer
- Tarmsykdommer
- Gastrointestinale neoplasmer
- Neoplasmer i fordøyelsessystemet
- Sykdommer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Kolorektale neoplasmer
- Intestinale neoplasmer
- Kolonsykdommer
- Kolon neoplasmer
- Undersøkelsesteknikker
- Kliniske laboratorieteknikker
- Diagnostiske teknikker og prosedyrer
- Diagnose
- Kirurgiske prosedyrer, operativ
- Minimalt invasive kirurgiske inngrep
- Cytologiske teknikker
- Cytodiagnose
- Diagnostiske teknikker, kirurgisk
- Endoskopi, gastrointestinal
- Endoskopi, fordøyelsessystem
- Diagnostiske teknikker, fordøyelsessystem
- Endoskopi
- Fordøyelsessystem kirurgiske inngrep
- Biopsi
- Prøvehåndtering
- Koloskopi
- Toripalimab
Andre studie-ID-numre
- STUDY00008833
- P30CA138292 (U.S. NIH-stipend/kontrakt)
- STUDY00008833 (Annen identifikator: Emory University Hospital/Winship Cancer Institute)
- NCI-2025-05423 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
- WINSHIP6483-24 (Annen identifikator: Emory University Hospital/Winship Cancer Institute)
Legemiddel- og utstyrsinformasjon, studiedokumenter
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