G-CSF in Patients With Anti-PD-1-axis Therapy-resistant Recurrent or Metastatic Nasopharyngeal Carcinoma

NCT ID: NCT05222009

Last Updated: 2022-02-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-24
• Study Completion Date: 2023-08-01

Brief Summary

Recurrence and metastasis are the main causes of treatment failure of NPC. Immunotherapy is an emerging cancer treatment method, which has less adverse reactions and longer duration compared with chemotherapy. At present, there are a large number of PATIENTS with anti-PD-1 resistance in clinical practice, who are faced with a significant decline in the efficacy of anti-PD-1 after treatment. However, without the synergistic effect of anti-PD-1, survival after chemotherapy alone will be significantly shortened. how to improve the efficacy of immunotherapy rechallenge so that a large number of potential patients can benefit from immunotherapy is an urgent problem to be solved at present.

Studies have shown that G-CSF can significantly increase the proportion of effector cells dominated by CD4+ T cells, improve the diversity of peripheral blood TCR, thus regulate the immune status of tumor patients. Therefore, G-CSF may have a synergistic effect on anti-PD-1. This study intends to explore whether the addition of G-CSF can restore the efficacy of anti-PD-1 in drug-resistant NPC patients through a prospective clinical trial.

Conditions

Granulocyte Colony-Stimulating Factor; PD-1 Inhibitor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

G-CSF arm1

PD-1 inhibitor resistance regimen+ G-CSF 3mg

Group Type: EXPERIMENTAL

PEG-rhG-CSF

Intervention Type: DRUG

PEG-rhG-CSF, 3mg, D1, Q3W, subcutaneous injection, until stop using PD-(L)1 inhibitor, progressive disease (PD) or unacceptable toxicity. Meanwhile, the original maintenance regimen--PD-(L)1 inhibitor ± VEGFR/EGFR TKI/Ab--continues.

G-CSF arm2

PD-1 inhibitor resistance regimen+ G-CSF 6mg

Group Type: EXPERIMENTAL

PEG-rhG-CSF

Intervention Type: DRUG

PEG-rhG-CSF, 6mg, D1, Q3W, subcutaneous injection, until stop using PD-(L)1 inhibitor, progressive disease (PD) or unacceptable toxicity. Meanwhile, the original maintenance regimen--PD-(L)1 inhibitor ± VEGFR/EGFR TKI/Ab--continues.

Interventions

PEG-rhG-CSF

PEG-rhG-CSF, 3mg, D1, Q3W, subcutaneous injection, until stop using PD-(L)1 inhibitor, progressive disease (PD) or unacceptable toxicity. Meanwhile, the original maintenance regimen--PD-(L)1 inhibitor ± VEGFR/EGFR TKI/Ab--continues.

Intervention Type: DRUG

PEG-rhG-CSF

PEG-rhG-CSF, 6mg, D1, Q3W, subcutaneous injection, until stop using PD-(L)1 inhibitor, progressive disease (PD) or unacceptable toxicity. Meanwhile, the original maintenance regimen--PD-(L)1 inhibitor ± VEGFR/EGFR TKI/Ab--continues.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female; 18-75 years of age.

2. Subjects diagnosed with pathological confirmed non-keratinizing (WHO-II/III) metastatic NPC, or subjects with recurrent NPC that is unfit for local treatment

3. Received prior treatment with platinum agents and PD-(L)1 inhibitors.

4. Developed acquired resistant (AR) to PD-(L)1 inhibitors following the anti-PD-1/L1 or combined with anti-target agent (VEGFR/EGFR TKI/Ab) maintenance therapy. (AR defined as disease progression after partial or complete response).

5. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.

6. ECOG performance status of 0 or 1.

7. Have recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to any anti-tumor therapy 4 weeks earlier. Except for hair loss, hair color change, nail change, fatigue, etc., which do not pose safety risks to subjects.

8. Life expectancy more than 12 weeks.

9. Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment) as determined by:

Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L; Hemoglobin ≥ 9 g/dL; serum total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN), (for subjects with liver metastases, TBIL ≤3×ULN ; ALT and AST≤5×ULN); Creatinine ≤1.5×ULN or creatinine clearance rate≥50 ml/min (Cockcroft-Gault formula); serum albumin ≥28 g/L; INR, APTT≤1.5 x ULN.

10. Female subjects agree not to be pregnant or lactating from beginning of the study screening through at least 3 months after receiving the last dose of study treatment. Both men and women of reproductive potential must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy.

11. Be willing and able to provide written informed consent/assent for the trial.

Exclusion Criteria

1. Known history of any ≥ grade 3 immune-related toxicity.

2. Known history of hypersensitivity to any components of the PEG-rhG -CSF formulation.

3. Received G-CSF concurrent with anti-PD-(L)1 antibody combined with anti-target agent (VEGFR/EGFR TKI/Ab) maintenance therapy. (Patients who received G-CSF to prevent and treat febrile neutropenia secondary to chemotherapy are permitted)

4. Prior chemotherapy, targeted small molecule therapy, or radical therapy within 2 weeks prior to Study Day 1

5. Diagnosed and/or treated additional malignancy within 5 years of enrollment, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast carcinoma.

6. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.

7. Active central nervous system metastases and/or carcinomatous meningitis

8. Severe, uncontrolled angiocardiopathy (heart failure > class II NYHA, unstable angina, myocardial infarction within past 1 year, supraventricular or ventricular arrhythmia which need medical intervention, or QT interval male ≥ 450 ms, female ≥ 470 ms.).

9. History of non-infectious pneumonitis that required steroids or current pneumonitis

10. Active infection requiring systemic therapy

11. Be known to have active tuberculosis.

12. Human immunodeficiency virus (HIV) positive

13. Hepatitis B or C positive

14. Live vaccine within 30 days of planned start of study drug

15. Underlying medical condition that, in the Investigator's opinion, would increase the risks of study drug administration or obscure the interpretation of toxicity determination or adverse events.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Ming-Yuan Chen

Chief physician, Proffessor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Ming-Yuan Chen, MD, PhD

Role: CONTACT

chmingy@mail.sysu.edu.cn

86-20-8734-3361

Xi Ding, MD

Role: CONTACT

dingxi@sysucc.org.cn

Facility Contacts

Ming-Yuan Chen, MD,PhD

Role: primary

chenmy@sysucc.org.cn

86-20-8734-2422

Other Identifiers

SYSUCC-CMY-2021-1214

Identifier Type: -

Identifier Source: org_study_id