NCT04605562

Brief Summary

This is a phase 2, open-label, umbrella study, with the purpose to evaluate the therapeutic efficacy and safety of chemoradiotherapy in combination with immunotherapy and/or targeted treatment in high-risk locoregionally advanced nasopharyngeal carcinoma. The specific grouping of patients' depends on the SYSUCC immune subtyping based on 100+ gene panel testing.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
206

participants targeted

Target at P75+ for phase_2

Timeline
7mo left

Started Jun 2022

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress87%
Jun 2022Dec 2026

First Submitted

Initial submission to the registry

October 22, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 28, 2020

Completed
1.6 years until next milestone

Study Start

First participant enrolled

June 1, 2022

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Last Updated

September 5, 2021

Status Verified

September 1, 2021

Enrollment Period

4.5 years

First QC Date

October 22, 2020

Last Update Submit

September 2, 2021

Conditions

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

  • Failure-free survival (FFS)

    Failure-free survival is measured from day of diagnosis until treatment failure, death from any cause, or last follow-up visit, whichever occurred first

    3-year

Secondary Outcomes (4)

  • Overall survival (OS)

    3-year

  • Distant failure-free survival (DFFS)

    3-year

  • Incidence rate of investigator-reported adverse events (AEs)

    3-year

  • Incidence rate of patient-reported adverse events (AEs)

    3-year

Study Arms (3)

IC+CCRT with palbociclib

EXPERIMENTAL

If patients were non-Immune Subtype.

Drug: GP+DDPDrug: PalbociclibRadiation: Intensity-modulated radiotherapy

IC+CCRT with galunisertib and PD-1 blocking antibody

EXPERIMENTAL

If patients were Evaded Immune Subtype.

Drug: GP+DDPRadiation: Intensity-modulated radiotherapyDrug: PD-1 blocking antibodyDrug: Galunisertib

IC+CCRT with PD-1 blocking antibody

EXPERIMENTAL

If patients were Active Immune Subtype.

Drug: GP+DDPRadiation: Intensity-modulated radiotherapyDrug: PD-1 blocking antibody

Interventions

GP+DDPDRUG

Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles; induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation

IC+CCRT with PD-1 blocking antibodyIC+CCRT with galunisertib and PD-1 blocking antibodyIC+CCRT with palbociclib
PalbociclibDRUG

Administered orally

IC+CCRT with palbociclib
Intensity-modulated radiotherapyRADIATION

Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day

IC+CCRT with PD-1 blocking antibodyIC+CCRT with galunisertib and PD-1 blocking antibodyIC+CCRT with palbociclib
PD-1 blocking antibodyDRUG

Administered every 3 weeks

IC+CCRT with PD-1 blocking antibodyIC+CCRT with galunisertib and PD-1 blocking antibody
GalunisertibDRUG

Administered orally

IC+CCRT with galunisertib and PD-1 blocking antibody

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age: 18 to 65;
  • Pathological type: non-keratinizing carcinoma (World Health Organization criteria);
  • Diagnosed with LANPC (T4N1, T1-4N2-3) according to the 8th edition clinical staging system of the American Joint Committee on Cancer \[AJCC\]/Union for International Cancer Control \[UICC\];
  • ECOG performance score: 0 to 1;
  • Normal bone marrow function: white blood cell count \> 4×109/L, hemoglobin \> 90g/L, platelet count \> 100×109/L;

You may not qualify if:

  • Normal liver and kidney function: total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine transaminase and aspartate transaminase ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; creatinine clearance rate ≥ 60 ml/min;
  • Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;
  • Subjects with pregnancy ability must agree to use reliable contraceptive measures from screening to 1 year after treatment.
  • Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA \> 1×10E3 copies/ml; anti-hepatitis C virus positive;
  • Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune deficiency syndrome (AIDS);
  • Active tuberculosis: active tuberculosis in the past 1 year should be excluded regardless with treatment; history of active tuberculosis over 1 year should be excluded except that previous regulatory anti-tuberculosis treatment is proved;
  • Active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia);
  • Previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
  • Chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day) or any other form of immunosuppressive therapy. Subjects who used inhaled or topical corticosteroids were eligible;
  • Uncontrolled heart disease, for example: 1) heart failure (NYHA level ≥ 2); 2) unstable angina; 3) myocardial infarction in past 1 year; 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
  • Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);
  • Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
  • Allergy to macromolecular protein preparations, or any component of the intervention drugs;
  • Active infection requiring systemic treatment;
  • History of organ transplantation;
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

palbociclibRadiotherapy, Intensity-ModulatedLY-2157299

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNasopharyngeal NeoplasmsPharyngeal NeoplasmsOtorhinolaryngologic NeoplasmsHead and Neck NeoplasmsNeoplasms by SiteNasopharyngeal DiseasesPharyngeal DiseasesStomatognathic DiseasesOtorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, ConformalRadiotherapy, Computer-AssistedRadiotherapyTherapeutics

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof

Study Record Dates

First Submitted

October 22, 2020

First Posted

October 28, 2020

Study Start

June 1, 2022

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Last Updated

September 5, 2021

Record last verified: 2021-09

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)