NEO-SPACE Trial: Pembrolizumab and Chemoradiation in Nasopharyngeal Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03734809|
Recruitment Status : Recruiting
First Posted : November 8, 2018
Last Update Posted : June 22, 2020
|Condition or disease||Intervention/treatment||Phase|
|NPC||Drug: Pembrolizumab||Phase 2|
Nasopharyngeal cancer (NPC) is a predominantly Asian disease, with approximately 80% of the world's 86000 cases occurring in Asian countries (12). With advances in radiation technology such as intensity modulation radiotherapy (IMRT), local and nodal control exceeds 85-90% in most reported series. Distant metastasis remains the main mode of failure, particularly in locally advanced NPC. As an example, in a study by Pan et al (13), 5 years local and nodal control of 86% and 89% was achieved with concurrent chemo-IMRT respectively, but distant failure free survival of 77% and 72% was reported for patients with T4 and N3 disease respectively (AJCC 8th edition).
Current strategies to reduce distant metastasis, including the use of adjuvant chemotherapy have been inconclusive. One major disadvantage of adjuvant chemotherapy following the completion of chemoradiation is that approximately half of patients are unable to complete the full 3 cycles of adjuvant chemotherapy, due to treatment related toxicities. The use of induction chemotherapy has two potential benefits: the first is to downsize the tumour, making radiotherapy more tolerable; the second, it allows for patients to be able to complete the chemotherapy before the onset of chemoradiation associated toxicities.
There are at least two studies now supporting the use of induction chemotherapy. A recent publication by Ma et al (14), showed the addition of induction docetaxel, cisplatin and fluorouracil prior to concurrent chemoradiation resulted in 8% improvement (80% vs 72%) in 3-year failure-free survival. Similarly, Cao et al showed that 2 cycles of cisplatin and fluorouracil prior to chemoradiation improved the 3 years disease free survival in patients (15).
Gemcitabine and cisplatin has been shown to be more effective than 5-FU plus cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (16). There are currently no studies looking at the addition of anti-PD-1 monoclonal antibody such as pembrolizumab either in the in the induction or maintenance setting. Hence, we are proposing the use of pembrolizumab in combination with 2 cycles of gemcitabine and cisplatin chemotherapy followed by concurrent chemoradiation. Following completion of chemoradiation, patients will receive maintenance pembrolizumab for total treatment duration of one year. The main objective of this Phase II study is to test the safety, efficacy and tolerability of this combination in the setting of locally advanced NPC (limited to T4 or N3, stage IVA by UICC 8th edition), as this group has the greatest risk of recurrence after the current standard treatment.
Preliminary evidence supporting the clinical efficacy of pembrolizumab monotherapy in NPC came from the KEYNOTE-028 trial, which was a global, nonrandomized, multi-cohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (17). Key eligibility criteria for the NPC cohort included unresectable or metastatic disease, failure on prior standard therapy, and PD-L1 expression in 1% or more of tumor cells or tumor-infiltrating lymphocytes. Patients received pembrolizumab 10 mg/kg every 2 weeks up to 2 years or until disease progression or unacceptable toxicity. In the initial report, twenty-seven NPC patients was evaluated. Median age was 52.0 years (range, 18 to 68 years); 92.6% received prior therapies for recurrent or metastatic NPC; 70.4% had received three or more therapies. Partial response and stable disease were observed in seven and 14 patients, respectively, for an ORR of 25.9% (95% CI, 11.1 to 46.3) over a median follow-up of 20 months. Drug-related adverse events that occurred in 15% or more of patients included rash (25.9%), pruritus (25.9%), pain (22.2%), hypothyroidism (18.5%), and fatigue (18.5%). Grade ≥ 3 drug-related adverse events occurred in eight patients (29.6%), and there was one drug-related death (sepsis). It was concluded that pembrolizumab demonstrated antitumor activity and a manageable safety profile in patients with recurrent or metastatic NPC.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NEO-SPACE Trial: Neoadjuvant Pembrolizumab-Gemcitabine-Cisplatin Followed by Concurrent Pembrolizumab-Chemoradiation and Maintenance Pembrolizumab for Stage IVA Nasopharyngeal Cancer|
|Actual Study Start Date :||May 3, 2019|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2023|
Total 51 weeks for 17 doses of pembrolizumab:
200mg every 3 weeks infusion
Other Name: Concurrent Chemoradiation
- Two-year progression free survival [ Time Frame: 2 years ]
- Grade 4 mucositis/skin reaction or any Grade 5 adverse event assessed to be definitely, probably, or possibly related to protocol treatment during the first year [ Time Frame: during the first year ]use toxicity chart to capture
- Grade 4 mucositis/skin reaction or any Grade 5 adverse event assessed to be definitely, probably, or possibly related to protocol treatment occurring after the first year [ Time Frame: after the first year ]
- Patient tolerability to each component (neoadjuvant, concurrent and maintenance part) of the protocol treatment regimen [ Time Frame: 2 year ]
- Other ≥ Grade 3 adverse events [ Time Frame: 2 year ]
- Death during or within 30 days of discontinuation of protocol treatment [ Time Frame: during or within 30 days ]
- One- and two-year distant metastases rates [ Time Frame: 1 year and 2 years ]
- One- and two-year local-regional progression rates [ Time Frame: 1 year and 2 years ]
- One- and two-year rates of second primary cancer [ Time Frame: 1 year and 2 years ]
- One- and two-year overall survival rates [ Time Frame: 1 year and 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03734809
|Contact: Anthony TC CHAN, MDemail@example.com|
|Contact: Edwin P HUI, MDfirstname.lastname@example.org|
|Department of Clinical Oncology, Prince of Wales Hospital||Recruiting|
|Hong Kong, Hong Kong|
|Contact: Anthony TC Chan, MD 3505 2119 email@example.com|
|Contact: Candy Yuen, RN 3505 1040 firstname.lastname@example.org|
|National Cancer Centre of Singapore||Not yet recruiting|
|Contact: Darren WT Lim, MD email@example.com|
|Contact: Yoke Lim YL Soong, MD Soong.yoke.lim@Singhealth.com.sg|