Umbrella Biomarker-Guided Therapy in NPC

NCT ID: NCT04605562

Last Updated: 2021-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-30
• Study Completion Date: 2026-12-31

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.

Detailed Description

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. The molecular subgroups include the Active, Evaded and non-Immune Subtypes. New treatment arms may be added and/or existing treatment arms may be closed during the study course on the basis of ongoing efficacy and safety as well as the current treatments available.

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IC+CCRT with palbociclib

If patients were non-Immune Subtype.

Group Type: EXPERIMENTAL

GP+DDP

Intervention Type: DRUG

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

Palbociclib

Intervention Type: DRUG

Administered orally

Intensity-modulated radiotherapy

Intervention Type: RADIATION

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

IC+CCRT with galunisertib and PD-1 blocking antibody

If patients were Evaded Immune Subtype.

Group Type: EXPERIMENTAL

GP+DDP

Intervention Type: DRUG

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

Intensity-modulated radiotherapy

Intervention Type: RADIATION

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

PD-1 blocking antibody

Intervention Type: DRUG

Administered every 3 weeks

Galunisertib

Intervention Type: DRUG

Administered orally

IC+CCRT with PD-1 blocking antibody

If patients were Active Immune Subtype.

Group Type: EXPERIMENTAL

GP+DDP

Intervention Type: DRUG

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

Intensity-modulated radiotherapy

Intervention Type: RADIATION

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

PD-1 blocking antibody

Intervention Type: DRUG

Administered every 3 weeks

Interventions

GP+DDP

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

Intervention Type: DRUG

Palbociclib

Administered orally

Intervention Type: DRUG

Intensity-modulated radiotherapy

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

Intervention Type: RADIATION

PD-1 blocking antibody

Administered every 3 weeks

Intervention Type: DRUG

Galunisertib

Administered orally

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age: 18 to 65;

2. Pathological type: non-keratinizing carcinoma (World Health Organization criteria);

3. 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];

4. ECOG performance score: 0 to 1;

5. Normal bone marrow function: white blood cell count > 4×109/L, hemoglobin > 90g/L, platelet count > 100×109/L;

Exclusion Criteria

7. 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;

8. 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;

9. Subjects with pregnancy ability must agree to use reliable contraceptive measures from screening to 1 year after treatment.

1. Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA > 1×10E3 copies/ml; anti-hepatitis C virus positive;

2. Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune deficiency syndrome (AIDS);

3. 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;

4. 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);

5. Previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;

6. 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;

7. 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;

8. Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);

9. Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;

10. Allergy to macromolecular protein preparations, or any component of the intervention drugs;

11. Active infection requiring systemic treatment;

12. History of organ transplantation;

13. History of psychotropic disease, alcoholism or drug abuse; other situation assessed by the investigators that may compromise the safety or compliance of patients, such as serious disease requiring timely treatment (including mental illness), severe laboratory abnormalities, or family-social risk factors.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Jun Ma, MD

Prof

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

SZR2019-069

Identifier Type: -

Identifier Source: org_study_id