- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT04651127
Anti-PD-1 Antibody Combined With Histone Deacetylase Inhibitor in Patients With Advanced Cervical Cancer
Toripalimab, a Anti-PD-1 Antibody, and Histone Deacetylase Inhibitor Chidamide in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer, a Multicenter, Open-label, Single-arm, Phase Ib/II Trial
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
Studietype
Registrering (Forventet)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: Chunyan Lan
- Telefonnummer: +862087343870
- E-post: lanchy@sysucc.org.cn
Studer Kontakt Backup
- Navn: Xin Huang
- Telefonnummer: +862087343104
- E-post: huangxin@sysucc.org.cn
Studiesteder
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广东
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Guangzhou, 广东, Kina, 510060
- Rekruttering
- Sun Yat-Sen University Cancer Centre
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Ta kontakt med:
- Chunyan Lan
- Telefonnummer: +862087343870
- E-post: lanchy@sysucc.org.cn
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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:
- Signed Informed Consent Form (ICF).
- Patients must have histologically confirmed diagnosis of metastatic, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
- Age ≥ 18 years and ≤ 70 years.
- Patients must have measurable disease per RECIST v1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy exceeds 3 months.
Patients must have progressed on at least one line of platinum-based systemic therapy.
Note: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic cervical cancer. However, adjuvant chemotherapy could be counted as one prior regimen in patients who had recurrence during or within 6 months of completion of therapy.
Patients must have adequate organ function as defined by the following criteria:
- Absolute neutrophil count (ANC) (≥ 1.5×10^9/L), hemoglobin of ≥ 90 g/L, platelets ≥ 80 ×10^9/L
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
- Baseline albumin ≥ 28 g/L
- Thyroid-stimulating hormone (TSH) levels ≤ 1 × ULN (however, patients with free Triiodothyronine [FT3] or free Thyroxine [FT4] levels ≤ 1 × ULN may be enrolled)
Exclusion Criteria:
- Prior exposure to immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies, or prior exposure to HDAC inhibitors.
- Any condition requiring systemic treatment with corticosteroids (>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before first dose of study drug. Corticosteroids for topical use, nasal spray, and inhaled steroids are allowed.
- Active autoimmune diseases that require systemic treatment. Alternative treatments (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are permitted.
- Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association [NYHA] class > 2), unstable or severe angina, severe acute myocardial infarction within 1 year before enrollment, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.
- Arterial or venous thrombosis within 6 months before enrollment
- Uncontrolled hypertension defined as systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg despite antihypertensive drugs.
- Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
- Coagulation abnormalities (INR > 2.0, PT > 16s), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
- Has known active central nervous system metastases.
- Patients had a diagnosed and/or treated additional malignancy within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has a known history of immunodeficiency including human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
- Has known active Hepatitis B or Hepatitis C.
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 |
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Eksperimentell: Toripalimab + Chidamide Arm
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In combination dose finding phase, phase 1b will begin with Dose Level 1: chidamide 30 mg/day orally (twice a week) and toripalimab (240mg q3w, intravenously) will be administered to eligible subjects on a 21-day treatment cycle.
Two dose de-escalation steps are included: Dose Level 2 (chidamide 25 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously) and Dose Level 3 (chidamide 20 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously).
If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week).
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
To evaluate the safety and tolerability of the combination of toripalimab and chidamide (Phase Ib)
Tidsramme: first 28 days of treatment
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Dose-limiting toxicities (DLTs) are defined as: grade 3 febrile neutropenia, grade 4 hematologic toxicities, and grade 3 non-hematologic toxicities according to CTCAE v5.0
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first 28 days of treatment
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Objective Response Rate (ORR) (Phase II)
Tidsramme: from the first drug administration up to two years
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ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
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from the first drug administration up to two years
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Progresjonsfri overlevelse (PFS)
Tidsramme: fra første legemiddeladministrasjon opp til to år
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Tid fra datoen for første studiebehandlingsadministrasjon til datoen for første dokumenterte tumorprogresjon eller død på grunn av en hvilken som helst årsak, avhengig av hva som inntreffer først.
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fra første legemiddeladministrasjon opp til to år
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Varighet av respons (DOR)
Tidsramme: fra første legemiddeladministrasjon opp til to år
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Tid fra første dokumenterte respons (CR eller PR) til dokumentert sykdomsprogresjon eller død, avhengig av hva som inntreffer først.
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fra første legemiddeladministrasjon opp til to år
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Disease Control Rate (DCR)
Tidsramme: from the first drug administration up to two years
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Proportion of patients whose best overall response is either CR, PR, or SD according to RECIST v1.1.
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from the first drug administration up to two years
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Overall survival (OS)
Tidsramme: from the first drug administration up to two years
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Time from the date of first study treatment administration to the date of death due to any cause.
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from the first drug administration up to two years
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Safety and tolerability
Tidsramme: up to 90 days after last study treatment administration
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Incidence of Adverse Event reported per CTCAE v5.0
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up to 90 days after last study treatment administration
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Xin Huang, Sun Yat-Sen University Cancer Centre
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Forventet)
Studiet fullført (Forventet)
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
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- B2020-229-01
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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