Evaluation of Pembrolizumab and Olaparib in Adult Patients with Recurrent/Metastatic, Platinum-Resistant Nasopharyngeal Carcinoma
- Trial ID
- 2024-511901-52-00
- Protocol
- POINT
- Sponsor
- Fondazione GONO Plus
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **increase in response rate** with the combination of pembrolizumab and olaparib in comparison with historical data of immunotherapy alone in adult patients with recurrent/metastatic, platinum-resistant nasopharyngeal cancer. This is clinically relevant as it aims to improve treatment outcomes in a patient population with limited therapeutic options.
Secondary objectives include:
- Assessment of **treatment safety** to ensure the combination therapy is well-tolerated.
- Evaluation of **progression-free survival (PFS)** to determine the duration patients remain free from disease progression.
- Measurement of **overall survival (OS)** to assess the impact of the treatment on patient longevity.
- Analysis of **quality of life**, using the EORTC QLQ HN43 questionnaire, to understand the treatment's effect on patients' daily living.
- Investigation of the **prognostic role at baseline** of various parameters, including tissue and blood samples, to identify potential biomarkers for treatment response and prognosis.
Participants
The clinical trial involves **adult patients** diagnosed with recurrent or metastatic, platinum-resistant nasopharyngeal cancer. The study population includes both male and female participants who are at least 18 years old, with an **Eastern Cooperative Oncology Group (ECOG) performance status** of 0 to 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must have adequate organ function and a life expectancy of at least 16 weeks. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria require participants to have a histologically confirmed diagnosis of nasopharyngeal carcinoma, with disease progression within six months following previous platinum-based treatment. Lifestyle considerations such as diet and physical activity are not specified. The trial population was selected based on specific inclusion criteria, including the requirement for measurable disease based on RECIST 1.1 and the provision of written informed consent. The sponsor has not disclosed any additional lifestyle or demographic details.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a combination treatment involving **pembrolizumab** and **olaparib** in adult patients with recurrent/metastatic, platinum-resistant nasopharyngeal cancer. This is a phase II, randomized, double-blind, controlled study aimed at increasing the response rate compared to historical data with immunotherapy alone. The trial is expected to last until April 2028, with recruitment having commenced in April 2022. Participants will be involved in the study for a maximum treatment period of 36 months, subject to their continued eligibility and absence of adverse conditions warranting early termination.
The study involves a series of structured visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, organ function, and disease characteristics. Participants must provide written informed consent and demonstrate measurable disease based on RECIST 1.1 criteria. Following the screening, participants will undergo regular follow-up visits to monitor treatment response and adverse events, with assessments conducted according to the Response Evaluation Criteria in Solid Tumors Version 1.1. The primary endpoint is the Objective Response Rate (ORR) by the third radiological examination at week 27. Secondary endpoints include the rate of adverse events, progression-free survival, overall survival, and changes in quality of life.
Participants will receive **pembrolizumab** via intravenous infusion and **olaparib** orally, with dosages not exceeding 200 mg and 600 mg daily, respectively. The study will continue until the end-of-study visit, where final assessments will be made. Conditions that may lead to early termination include significant adverse events, disease progression, or withdrawal of consent. The trial's design ensures rigorous monitoring and evaluation to achieve its objectives while maintaining participant safety and data integrity.
Treatment
The clinical trial involves the administration of **pembrolizumab**, marketed under the name Keytruda, which is provided as a 25 mg/mL concentrate for solution for infusion. This pharmaceutical form is intended for **intravenous infusion**. The maximum daily and total dose of pembrolizumab is 200 mg, with a treatment period extending up to 36 months. Pembrolizumab is a protein-based therapeutic agent developed by Merck Sharp & Dohme B.V. and is classified under the ATC code L01FF02. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.
In addition to pembrolizumab, the trial includes the administration of **olaparib**, which is provided in the form of film-coated tablets. Olaparib is administered orally, with a maximum daily and total dose of 600 mg, also over a treatment period of up to 36 months. The active substance, olaparib, is a chemical compound developed by Merck & Co. Inc. The trial utilizes two separate product entries for olaparib, both with the same pharmaceutical form and dosing parameters. Participant compliance with the oral administration schedule is monitored to ensure accurate dosing and adherence to the trial protocol.
Efficacy
Efficacy in the clinical trial evaluating the combination of **pembrolizumab** and **olaparib** in recurrent/metastatic, platinum-resistant nasopharyngeal cancer will be assessed using several endpoints. The primary endpoint is the Objective Response Rate (ORR), which will be determined by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. ORR is defined as the percentage of participants who achieve a Complete Response (CR), characterized by the disappearance of all target lesions, or a Partial Response (PR), indicated by at least a 30% decrease in the sum of diameters of target lesions. This assessment will be conducted by the third radiological examination, scheduled for week 27.
Secondary endpoints include the rate of patients experiencing adverse events of grade 3 or higher, as well as all-grade adverse events classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Progression-Free Survival (PFS) will also be evaluated, defined as the time from the first dose to the first documented progressive disease (PD) per RECIST 1.1 or death from any cause, whichever occurs first. Overall Survival (OS) will be measured from the first dose to death due to any cause, with follow-up continuing for up to three years since the last patient's first visit. Additionally, changes in Quality of Life (QoL) from baseline will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43).
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male/female participants who are at least 18 years old
- The participant (or legally acceptable representative) provides written informed consent.
- Histologically confirmed diagnosis of nasopharyngeal carcinoma.
- Disease not amenable of surgical resection or irradiation with curative intent.
- Disease progressing within 6 months since previous platinum-based systemic treatment (as concomitant to RT or as first line treatment for RM NPC).
- Male participants: A male participant must agree to use contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 6 months (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:o Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR o A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 6 months after the last dose of study treatment.
- Measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the start of study treatment.
- Patients must have a life expectancy ≥ 16 weeks.
- Adequate organ function as defined in the following table (Table 5.1). Specimens must be collected within 10 days prior to the start of study treatment.
Exclusion Criteria
- WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
- Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
- Prior radiotherapy within 2 weeks of study intervention beginning. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- Currently participating in or has participated in a study with an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided those are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- Severe hypersensitivity (≥Grade 3) to study treatment drugs and/or any of its excipients.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 07 Apr 2022 | 30 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 200 | 36 | PRD4323105 |
Olaparib | Test | FILM-COATED TABLET | ORAL | 600 | 36 | PRD9414227 |
Olaparib | Test | FILM-COATED TABLET | ORAL | 600 | 36 | PRD9414228 |