A Clinical Study of QL1706 Combined With Chemotherapy as Neoadjuvant Therapy for High-Risk Locally Advanced Cervical Cancer
A Randomized, Multicenter, Phase III Study of Iparomlimab and Tuvonralimab (QL1706) Combined With Chemotherapy as Neoadjuvant Therapy for Locally Advanced Cervical Cancer
Studienübersicht
Status
Status
Bedingungen
Bedingungen
Intervention / Behandlung
Intervention / Behandlung
Studientyp
Studientyp
Einschreibung (Geschätzt)
Einschreibung
Phase
Phase
- Phase 3
Kontakte und Standorte
Studienkontakt
Studienkontakt
- Name: Qin Xu
- Telefonnummer: 13950419396
- E-Mail: xuqin@fjmu.edu.cn
Studienorte
-
-
Fujian
-
Fuzhou, Fujian, China, 350014
- Fujian Cancer Hospital
-
Kontakt:
- Qin Xu
- Telefonnummer: 13950419396
- E-Mail: xuqin@fjmu.edu.cn
-
-
Teilnahmekriterien
Zulassungskriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Beschreibung
Inclusion Criteria:
- 1) Age: 18-75 years; 2) Histologically confirmed cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma; 3) Locally advanced disease (Stage III-IVA per FIGO 2018 staging criteria, including IIIC1/IIIC2), confirmed by imaging evaluation; 4) ECOG performance status 0-1; 5) Expected to be able to complete external beam radiation therapy (EBRT) combined with brachytherapy; 6) No definite contraindications to radiotherapy; 7) Able to provide pathological specimens (≥18 qualified tissue slides) for biomarker testing; 8) No prior surgery, radiotherapy, chemotherapy, systemic therapy (including investigational drugs), or immunotherapy for cervical cancer; 9) At least one measurable lesion (per RECIST 1.1: ≥10 mm longest diameter for non-lymph node lesions on CT; ≥15 mm short axis for lymph node lesions on CT); 10) Expected survival ≥6 months; 11) Adequate major organ function. Hematology (without transfusion or blood products within 14 days): ANC ≥1.5×10⁹/L; platelets ≥80×10⁹/L; hemoglobin ≥9 g/dL. Biochemistry: total bilirubin <1.5×ULN; AST and ALT ≤2.5×ULN; serum creatinine ≤1.5×ULN, or creatinine clearance ≥40 mL/min (using the standard Cockcroft-Gault formula); 12) Participants have signed informed consent and agree to comply with follow-up; 13) Women of childbearing potential must agree to use effective contraception during the study and for at least 12 months after the last dose (postmenopausal women or women not of childbearing potential are exempt).
Exclusion Criteria:
- 1) Diagnosed with other malignancies within 5 years prior to first dose, excluding radically treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, radically excised carcinoma in situ, and/or papillary thyroid carcinoma; 2) Histologically confirmed small cell (neuroendocrine) cervical carcinoma, cervical carcinosarcoma, or gastric-type cervical adenocarcinoma; 3) FIGO 2018 Stage IVB disease; 4) Prior total hysterectomy (defined as removal of the entire uterus) or planned hysterectomy as part of initial cervical cancer treatment; 5) Bilateral hydronephrosis, unless at least one side has been stented or resolved by nephrostomy, or considered mild and not clinically significant by the investigator; 6) Anatomical or tumor geometric contraindications to intracavitary brachytherapy or combined intracavitary and interstitial brachytherapy, or any other contraindications; 7) Live vaccine administration within 30 days prior to first dose of study treatment; 8) Systemic immunostimulatory agents, colony-stimulating factors, interferons, interleukins, or vaccine combinations within 6 weeks or 5 half-lives (whichever is shorter) prior to Day 1 of Cycle 1; 9) Prior treatment with anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agents, or agents targeting other stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137); 10) Systemic anti-cancer therapy within 4 weeks prior to randomization, including investigational drugs; 11) Currently participating in or previously participated in a study with an investigational drug; 12) Contraindications to cisplatin use; 13) Diagnosed with immunodeficiency or receiving chronic systemic corticosteroid therapy (>10 mg/day prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to first study treatment; 14) Hypersensitivity to any study drug; 15) Active autoimmune disease requiring systemic therapy within the past 2 years; 16) History of (non-infectious) pneumonitis/interstitial lung disease requiring corticosteroids, or current pneumonitis/interstitial lung disease; 17) Active infection requiring systemic treatment; 18) Known history of human immunodeficiency virus (HIV) infection; 19) Known history of hepatitis B or known active hepatitis C viral infection; 20) Any condition, treatment, laboratory abnormality, or other circumstance that may increase risk associated with study participation or administration of study treatment, or may interfere with interpretation of study results, and judged by the investigator or sponsor to render the participant unsuitable for this study; 21) Known psychiatric or substance abuse disorders that would interfere with the participant's ability to comply with study requirements; 22) Prior allogeneic tissue/solid organ transplantation; 23) Evidence of metastatic disease per RECIST 1.1, including lymph nodes in the inguinal region or above the level of the L1 vertebral body; 24) Women with pregnancy desire, pregnant women, or breastfeeding women.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Anzahl der Arme
Waffen und Interventionen
Teilnehmergruppe / ArmTeilnehmergruppe / Arm |
Intervention / BehandlungIntervention / Behandlung |
|---|---|
|
Aktiver Komparator: Standard concurrent chemoradiotherapy(CCRT)
Standardmäßige gleichzeitige Radiochemotherapie akzeptieren
|
EBRT: 45-50.4Gy,
Brachytherapy: 6Gy ×5
Cisplatin 40mg/m2, qw×5
|
|
Experimental: Neoadjuvant Therapy Group
Participants in the experimental arm will receive 2 cycles of QL1706 + paclitaxel (albumin-bound) + Cisplatin/Carboplatin.
Following neoadjuvant therapy, patients will undergo EBRT + QL1706.
After EBRT completion, patients with clinical complete response (CCR) will receive brachytherapy at a dose of 600 cGy × 3 fractions; patients without CCR will receive brachytherapy at a dose of 600 cGy × 5 fractions.
Subsequent sequential QL1706 will be administered for up to 2 years, until disease progression, or unacceptable toxicity.
|
Neoadjuvant phase: total of 2 cycles.
Iparomlimab/Tuvonralimab 5mg/kg,D1,Q3W + albumin paclitaxel 90mg/m2, D1、8、15,Q3W+ Cisplatin 25mg/m2 or Carboplatin AUC = 1.5 , D1、8、15,Q3W
Following neoadjuvant therapy, patients will receive EBRT + QL1706.
After EBRT completion, brachytherapy dose is 600 cGy × 3 fractions for patients with clinical complete response (CCR), and 600 cGy × 5 fractions for non-CCR patients.
Iparomlimab/Tuvonralimab (QL1706) 5 mg/kg,D1,Q3W.
Will be administered for up to 2 years, until disease progression, or until unacceptable toxicity, whichever occurs first.
|
Was misst die Studie?
Primäre Ergebnismessungen
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Progression-Free Survival(PFS)
Zeitfenster: Up to approximately 60 months
|
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
|
Up to approximately 60 months
|
Sekundäre Ergebnismessungen
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Overall Survival (OS)
Zeitfenster: Up to approximately 60 months
|
OS is defined as the time from randomization to death due to any cause.
|
Up to approximately 60 months
|
|
Objective Response Rate (ORR)
Zeitfenster: Up to approximately 60 months
|
ORR is defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed investigator per RECIST 1.1
|
Up to approximately 60 months
|
|
Disease Control Rate (DCR)
Zeitfenster: Up to approximately 3 years
|
DCR is defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by investigator per RECIST 1.1
|
Up to approximately 3 years
|
|
Clinical Complete Response Rate, CCR
Zeitfenster: Up to approximately 6 months
|
Defined as the absence of measurable tumor lesions on clinical examination and imaging assessment, which may be adjunctively confirmed by necessary pathological examinations (such as cervical biopsy).
CCR is primarily used to guide brachytherapy dose stratification and is not used as a criterion for PFS event determination.
|
Up to approximately 6 months
|
|
Duration of Response (DOR)
Zeitfenster: Up to approximately 3 years
|
Assessed by investigators
|
Up to approximately 3 years
|
|
Time to Response (TTR)
Zeitfenster: Up to approximately 3 years
|
Assessed by investigators
|
Up to approximately 3 years
|
|
Time to Progression (TTP)
Zeitfenster: Up to approximately 3 years
|
Assessed by investigators
|
Up to approximately 3 years
|
|
Quality of Life Assessed by Patient-Reported Outcome Questionnaires (QoL)
Zeitfenster: Up to approximately 3 years
|
Quality of life will be assessed using EORTC QLQ-C30, EORTC QLQ-CX24, and EQ-5D questionnaires.
|
Up to approximately 3 years
|
|
Incidence of brachytherapy dose reduction
Zeitfenster: Up to approximately 6 months
|
Defined as the proportion of participants who, after completion of external beam radiotherapy (EBRT) and originally planned to receive the standard brachytherapy dose regimen (5 fractions), achieved the predefined clinical complete response (CCR) criteria and, upon investigator assessment, actually received a reduced number of brachytherapy fractions (3 fractions).
|
Up to approximately 6 months
|
|
Percentage of Participants With Adverse Events (AEs)
Zeitfenster: Up to approximately 3 years
|
Number of participants with adverse events (AEs) according to CTCAE 5.0
|
Up to approximately 3 years
|
Mitarbeiter und Ermittler
Sponsor
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Studienbeginn
Primärer Abschluss (Geschätzt)
Primärer Abschluss
Studienabschluss (Geschätzt)
Studienabschluss
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Zuerst gepostet
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes Update gepostet
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
Andere Studien-ID-Nummern
- QL-CC-QIBA-3078
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .