Phase II Prospective Study of Bintrafusp Alfa in Previously Treated Patients With Recurrent and Metastatic (R/M) Non-keratinizing Nasopharyngeal Carcinoma (NPC)

Nasopharyngeal Carcinoma Clinical Trial

Official title:

Phase II Prospective Study of Bintrafusp Alfa in Previously Treated Patients With Recurrent and Metastatic (R/M) Non-keratinizing Nasopharyngeal Carcinoma (NPC)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04284332
• Other study ID #: UW 19-675
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 28, 2020
• Est. completion date: January 30, 2023

Study information

• Verified date: February 2020
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This would be a phase II prospective single arm mono-institutional study conducted in Queen Mary Hospital (Hong Kong) assessing the efficacy and safety of bintrafusp alfa in previously treated patients with recurrent and metastatic (R/M) non-keratinizing nasopharyngeal carcinoma (NPC)

Description:

All the patients must be registered with the Investigator(s) prior to initiation of treatment. The registration desk will confirm all eligibility criteria and obtain essential information (including patient number).

Patients shall receive Bintrafusp alfa treatment through intravenous therapy every two weeks up until disease progression, unacceptable toxicity or for a maximum of 2 years. Survival Follow-up till 5 years will also be performed.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 37
• Est. completion date: January 30, 2023
• Est. primary completion date: January 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed non-keratinizing differentiated (World Health Organization WHO Type II) or undifferentiated (WHO Type III) nasopharyngeal carcinoma (NPC) that has recurred at regional or / and distant sites

• Measurable disease according to the RECIST criteria (version 1.1) for the evaluation of measurable disease

• Received one or more lines of chemotherapy, which must include prior treatment with a platinum agent either

• For the treatment of metastatic or recurrent disease

• Experienced progression of disease within 6 months following completion of a platinum-based combination therapy as part of (neo)-adjuvant therapy

• Male or female subjects with age: 18-79 years old

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

• No prior immunotherapy

• Written informed consent obtained for clinical trial participation and providing archival tumor tissue, if available

• Females of childbearing potential or non-sterilized male who are sexually active must use a highly effective method of contraception

• Females of childbearing potential must have negative serum or urine pregnancy test

• Have life expectancy = 3 months

• Adequate organ function as defined as:

• Absolute neutrophil count = 1.5 x 10^9/L

• Platelet count = 100 x 10^9/L

• Hemoglobin >= 8.0 g/dL

• Serum alanine aminotransferase ([ALT]; serum glutamate-pyruvate transferase [SGPT]), or serum aspartate aminotransferase [AST] where available at the center) < 2.5 x upper limit of normal (ULN), OR < 5 x ULN in the presence of liver metastases

• Serum total bilirubin < 2 x ULN

• Serum creatinine < 1.5 x ULN

Exclusion Criteria:

• Prior invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured

• Isolated local recurrence or persistent disease

• Has disease that is suitable for local therapy administrated with curative intent

• Severe, active co-morbidity

• Currently participating in and receiving clinical trial treatment or has participated in a trial of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment

• Has prior chemotherapy, targeted therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (= grade 1 or at baseline) from adverse events due to previous administered agent

• Untreated active central nervous system (CNS) metastatic disease, lepto-meningeal disease, or cord compression

• Clinically significant (active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (=New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.

• Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), or PD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2) agent or an antibody targeting other immuno-regulatory receptors or mechanisms

• Irritable bowel syndrome or other serious gastrointestinal chronic conditions associated with diarrhea within the past 3 years prior to the start of treatment

• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.

• On chronic systemic steroid or any other forms of immunosuppressive medication within 14 days prior to the treatment. Except:

• Intra-nasal, inhaled, topical steroids, or local steroid injection (e.g., intraarticular injection);

• Systemic corticosteroids at physiologic doses =10 mg/day of prednisone or equivalent;

• Steroids as premedication for hypersensitivity reactions due to bintrafusp alfa

• Active or prior documented autoimmune or inflammatory disorders in the past 2 years, except diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment

• Known active hepatitis B or known hepatitis C is detected; subjects who have been treated and now have an undetectable viral load are eligible

• History of primary immunodeficiency or solid organ transplantation

• Receipt of live, attenuated vaccine within 28 days prior to the study treatment

• Active infection requiring systemic therapy

• Severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)

• Females who are pregnant, lactating, or intend to become pregnant during their participation in the study

• Psychiatric disorders and substance (drug/alcohol) abuse

Related Conditions & MeSH terms

• Carcinoma
• Immunotherapy
• Nasopharyngeal Carcinoma
• NPC

Intervention

Drug:
• Bintrafusp alfa
Bintrafusp alfa will be administered intravenously every 2 weeks

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong

Sponsors (2)

Lead Sponsor	Collaborator
The University of Hong Kong	Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

Hong Kong, 

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* Note: There are 71 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of Objective Tumour Response	To evaluate the objective tumor response (ORR) to bintrafusp alfa in previously treated R/M NPC patients per response evaluation criteria of solid tumor (RECIST) version 1.1	from the date of first study treatment to the date of last study treatment, an average of 3 years
Secondary	Progression-Free survival assessment	To assess the progression-free survival (PFS) per RECIST version 1.1	from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years
Secondary	Time-to-progression (TTP) assessment	2. To assess the time-to-progression (TTP) per RECIST version 1.1	from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years
Secondary	Median survival	To assess the median survival	from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years
Secondary	Toxicity and Tolerability measurement	To measure the toxicities and tolerability in previously treated R/M NPC patients receiving bintrafusp alfa with the most updated version of CTCAE criteria	from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years
Secondary	Objective Response Rate (ORR), Progression Free Survival (PFS) and Time-To-Progression (TTP) evaluation	To evaluate ORR, PFS and TTP per immune-related RECIST (irRECIST)	from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years
Secondary	Survival rate assessment	To measure the survival rate in 12 months and 24 months	from the date of screening to radiographically documented progression according to mRECIST 1.1, assessed up to 3 years