Pembrolizumab and olaparib in recurrent/metastatic, platinum resistant nasopharyngeal cancer
- Conditions
- asopharyngeal cancerMedDRA version: 21.0Level: LLTClassification code 10028793Term: Nasopharyngeal carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004649-35-IT
- Lead Sponsor
- Fondazione GONO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 30
1.Male/female participants who are at least 18 years old
2.The participant (or legally acceptable representative) provides written informed consent.
3.Histologically confirmed diagnosis of nasopharyngeal carcinoma.
4.Disease not amenable of surgical resection or irradiation with curative intent.
5.Disease progressing within 6 months since previous platinum-based systemic treatment (as concomitant to RT or as first line treatment for RM NPC).
6.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:
oNot a woman of childbearing potential (WOCBP) as defined in Appendix 3
OR
oA 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.
7.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.
8.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.
9.Patients must have a life expectancy = 16 weeks.
10.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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7
1.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.
2.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).
3.Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
4.Prior radiotherapy within 2 weeks of study intervention start. 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.
5.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.
7.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.
8.Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
9.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.
11.Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
18.Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
19.Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
20.Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study therapy is 2 weeks.
25.Has had an allogenic tissue/solid organ transplant.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Increase in response rate with the treatment combination in comparison with historical data with immunotherapy alone.;Secondary Objective: •Treatment Safety<br>•Progression-Free Survival (PFS)<br>•Overall Survival (OS)<br>•Quality of life, measured with EORTC QLQ HN43 questionnaire;Primary end point(s): Objective Response Rate (ORR) as Assessed by Investigators according to Response Evaluation Criteria in Solid Tumors Version 1.1 by the 3rd radiological examination (week 27).<br>ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1.;Timepoint(s) of evaluation of this end point: Week 27- 3rd radiological examination
- Secondary Outcome Measures
Name Time Method