Nivolumab Plus Gemcitabine in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma-HN17-11 (HN17-11)

Phase II Study of Nivolumab Plus Gemcitabine in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma-HN17-11

NPC is a highly chemo-sensitive cancer. Platinum-containing doublet chemotherapy is regarded as the standard treatment for patients with recurrent or metastatic NPC, even though it has never been directly compared with supportive care. Until now, no randomized trials have defined the optimum regimens. At present, cisplatin plus continuous intravenous infusion of fluorouracil is widely used in patients with recurrent or metastatic nasopharyngeal carcinoma, with a response rate of 40-65%.

Gemcitabine single is active and tolerable agent for recurred or metastatic NPC. Response rate (RR) was 34% and progression-free survival (PFS) was 5.0 months . Moreover, gemcitabine reduces the frequency of CD11b+GR1+ myeloid suppressor cells. Gemcitabine-induced apoptosis of established tumours may enhance the dendritic cell dependent cross-presentation of tumor antigens to T cells. Gemcitabine can function in synergy with CD40 stimulation of T cells. Hence, theoretically gemcitabine can have synergistic effect with PD-1/PD-L1 blocking agent.

Immunotherapy with immune checkpoint inhibitors has gradually emerged as a promising treatment modality for head and necks squamous cell carcinoma and NPC.

Study Overview

• Status: Completed
• Conditions: Recurrent or Metastatic Nasopharyngeal Carcinom
• Intervention / Treatment: Drug: Gemcitabine+ nivolumab

Detailed Description

Based on these evidences which suggest a function for PD-1/PD-L1 in NPC and potential synergistic effect with gemcitabine, the use of nivolumab in recurred/metastatic NPC is reasonable and valuable. So we design this phase II study of nivolumab and gemcitabine in recurred/metastatic NPC which is common cancer in Asian.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Department of Internal Medicine, Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Histologically confirmed nasopharyngeal carcinoma
2. Recurred after local treatment or metastatic disease. Disease that is not amenable to surgery, radiation or combined modality therapy with curative intent
3. Received at least one line of palliative chemotherapy
4. Presence of at least one measurable target lesion for further evaluation according to RECIST 1.1 criteria. Progressive lesions after radiation therapy can also be a target lesion. However, patients who were refractory to initial CCRT with platinum therapy (recurred within 6 months) were excluded.
5. 20 years or older
6. ECOG performance status 0, 1
7. Adequate organ function ANC ≥ 1500/ μL Platelets ≥100,000/ μL Hemoglobin ≥ 9.0 g/dL Serum creatinine ≤1.5 x ULN Serum bilirubin ≤1.5 x ULN AST, ALT, ≤3.0 x ULN (regardless of liver metastasis)
8. A patient with the willingness to comply with the study protocol during the study period and capable of complying with it
9. A patient who signed the informed consent prior to the participation of the study and who understands that he/she has a right to withdrawal from participation in the study at any time without any disadvantages.

Exclusion Criteria:

1. A patient with no measurable disease
2. A patient with previous active or passive immunotherapy or immune check point blocking agents or gemcitabine.
3. Active HBV (HBV DNA is positive) or HCV (HCV RNA is detected) or HIV infection. (inactive HBsAg carrier with prophylactic antiviral treatment can be enrolled)
4. A pregnant or lactating patient
5. A patient of childbearing potential without being tested for pregnancy at baseline or with being tested for positive. (A postmenopausal woman with the amenorrhea period of at least 12 months or longer is considered to have non-childbearing potential)
6. A man or woman of childbearing potential who has no willingness to use a contraceptive measure during the study
7. A patient with history of another malignant disease within past 5 years, except curatively treated basal cell carcinoma of skin, early gastric cancer, and cervical carcinoma in situ.
8. A patient with history of uncontrolled seizures, central nervous system disorder or psychiatric disorders that are considered clinically significant by the investigator that would prohibit the understanding of informed consent or that may be considered to interfere with the compliance of the administration of the study medications.
9. A patient with clinically significant heart disease (e.g. congestive heart failure, symptomatic coronary artery diseases, cardiac arrhythmia, etc) or myocardial infarction within past 12 months.
10. Ongoing cardiac arrhythmia of grade ≥2, atrial fibrillation of any grade, or QTc interval>450msec for males or >470msec for female.
11. A patient with interstitial pneumonia or diffuse symptomatic fibrosis of the lungs
12. A patient with organ transplantation requiring immunosuppressive therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gemcitabine+ nivolumab; Nivolumab administration on D1 and D15 every cycle, with 3mg/kg with gmecitabine co-administration on D1 and D15 every cycle, with 1250mg/m2	Drug: Gemcitabine+ nivolumab; Gemcitabine+ nivolumab q 2wks; Other Names: Experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	the percentage of patients who have not experienced disease progression or death from any cause from the start of treatment.	From the first date of treatment to the date occurring disease progression or death from any cause

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2018
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): April 30, 2021

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: May 28, 2024
• First Posted (Actual): June 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Recurrence; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Gemcitabine
• Other Study ID Numbers: KCSG-HN-17-11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No