Concurrent Chemoradiation and Durvalumab for Locoregionally Advanced Nasopharyngeal Carcinoma

NCT04447612 | Unknown Phase 2 DMC

• 1 other identifier: UW 19-534
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a phase II randomized-controlled study on using durvalumab in combination with induction chemotherapy followed by concurrent chemoradiation and adjuvant durvalumab, compared to induction chemotherapy followed by concurrent chemoradiation for previously untreated locoregionally advanced stage III to IVA NPC. In parallel, the investigators will also perform collateral tumor and serum biomarker studies which will be correlated with the treatment response. The investigators will collect fresh tumour biopsies at pretreatment, then serially after induction chemotherapy and after concurrent chemoradiation to investigate the change in microenvironment of the tumour and the surrounding inflammatory cells before and after durvalumab. In addition, the investigators will also measure the change in number and intensity of PD-L1-positive circulating tumour cells (CTC) before and after durvalumab and evaluate their correlation with treatment response.

Conditions

Nasopharyngeal Carcinoma

Keywords

Nasopharyngeal carcinoma; Immune checkpoint inhibitors; Chemotherapy; Radiation therapy; Locoregionally advanced

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Progression-free survival

  36 months

Secondary Outcomes (4)

• Best objective response

  36 months

• Overall survival

  36 months

• Toxicity profile

  36 months

• Changes in the number of PD-L1 positive circulating tumor cells before and after induction chemotherapy and concurrent chemoradiation

  36 months

Study Arms (2)

Durvalumab arm

EXPERIMENTAL

Induction phase: Durvalumab 1500mg via intravenous infusion every 4 weeks, with chemotherapy gemcitabine 1000mg/m2 on day 1 and day 8 and cisplatin 100mg/m2 on day 1 via intravenous infusion every 3 weeks for 3 cycles. Concurrent phase: Durvalumab 1500mg via intravenous infusion every 4 weeks for 2 cycles, with cisplatin 100mg/m2 via intravenous infusion every 3 weeks for 3 cycles. Maintenance phase: Durvalumab 1500mg daily via intravenous infusion every 4 weeks for 8 cycles.

Drug: Durvalumab; Drug: Cisplatin; Drug: Gemcitabine

Standard of care arm

ACTIVE COMPARATOR

Induction phase: Chemotherapy with gemcitabine 1000mg/m2 on day 1 and day 8 and cisplatin 100mg/m2 on day 1 via intravenous infusion every 3 weeks for 3 cycles. Concurrent phase: Cisplatin 100mg/m2 on day 1 of radiation therapy via intravenous infusion every 3 weeks for 3 cycles.

Drug: Cisplatin; Drug: Gemcitabine

Interventions

Durvalumab DRUG

Intravenous infusion of durvalumab 1500mg every 4 weeks for 13 cycles (1 year), starting 1 week before start of induction chemotherapy

Also known as: MEDI4736

Durvalumab arm

Cisplatin DRUG

Induction phase: cisplatin 100mg/m2 on day 1 via intravenous infusion every 3 weeks for 3 cycles Concurrent phase: cisplatin 100mg/m2 starting on day 1 of radiation therapy via intravenous infusion every 3 weeks for 3 cycles

Durvalumab arm; Standard of care arm

Gemcitabine DRUG

Induction phase: gemcitabine 1000mg/m2 on day 1 and day 8 via intravenous infusion every 3 weeks for 3 cycles

Durvalumab arm; Standard of care arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have pathologically confirmed, previously untreated stage III-IVA nasopharyngeal carcinoma (staged by American Joint Committee on Cancer/Union International for Cancer Control 8th edition staging classification) who plan to receive radical chemoradiation +/- durvalumab.
• Fresh frozen tumour and archived formalin-fixed paraffin-embedded (FFPE) nasopharyngeal tumour specimens must be available for PD-L1 expression and/other biomarker correlation studies.
• Age between 18-75 years. (The age limit set at 75 years because a previous Hong Kong study showed that elderly patient \>70 years had poor tolerance to radiotherapy and worse survival for their NPC. Please refer to Sze et al. Radical radiotherapy for nasopharyngeal carcinoma in elderly patients: The importance of co-morbidity assessment Oral Oncology 2012;48:162-167.)
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• All eligible patients must be magnetic resonance imaging of T1, T2 and T1-contrast enhanced sequences of the head and neck region and PET-CT scan within 60 days of study entry
• Modified Charlson Comorbidity Score \<2
• Adult Comorbidity Evaluation (ACE)-27 Index \<2
• Pre-existing peripheral neuropathy ≤1
• Baseline creatinine clearance \>60ml/min, calculated by Cockcroft-Gault Formula or derived by collection of 24-hour urine.
• Males:
• Creatinine Clearance (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
• Females:
• Creatinine Clearance (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
• Adequate serum hematological function defined as:
• Absolute neutrophil count ≥1.5 × 109/l

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter.
• Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study.
• Has had a prior monoclonal antibody within 4 weeks or 5 half-lives, whichever is shorter, prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) within 3 weeks prior to administration of the study drug or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered agent. \*Note: Subjects with permanent ≤Grade 2 toxicities (e.g. neuropathy) or toxicities corrected through routine medical management (e.g. thyroid replacement for hypothyroidism), are an exception to this criterion and may qualify for the study. \*Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. \*Note: Subjects with ≤Grade 2 amylase or lipase elevations abnormalities that have no corresponding clinical manifestations (e.g. manifestation of pancreatitis), are an exception to this criterion and may qualify for the study.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy
• Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis).
• Has an active infection requiring intravenous systemic therapy or hospital admission.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV type 1/2 antibodies). Routine checking for Anti-HIV type 1 or Anti-HIV type 2 is not mandatory.
• Untreated hepatitis B infection. Patients with chronic hepatitis B infection (defined as HBsAg positive) are eligible if they have started anti-viral therapy for at least 1 month and is continuing anti-viral treatment throughout the whole duration of this study.
• Has received a live vaccine 30 days prior to the first dose of trial treatment.
• Has experienced Grade 4 toxicity on treatment with prior radiation.
• Has experienced Grade 3-4 intracranial toxicity (hypophysitis or central nervous system toxicity) with either prior intracranial radiation, anti programmed cell death-1 (PD-1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor therapy.
• Is taking \> 4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required \> 4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment.

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Department of Clinical Oncology, Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

durvalumab; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Victor Lee, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Victor Lee, MD

CONTACT

852-2255-4352; vhflee@hku.hk

Sandy Cheung, MSc

CONTACT

852-2255-4216; sandy718@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Model Details: Randomized-controlled trial

Study Record Dates

• First Submitted: June 21, 2020
• First Posted: June 25, 2020
• Study Start: June 1, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: June 25, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)