Induction Versus Adjuvant Gemcitabine/Cisplatin in Locally Advanced Non-metastatic Nasopharyngeal Carcinoma

NCT04898374 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: HNIC-NP
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The standard of care for locally advanced nasopharyngeal carcinoma is radical chemoradiation(CRT).Recent advances in radiation techniques and supportive measures resulted in improvemnent of locoregional control and quality of life.However distant failure is still the main challenging reason of poor survival Addition of systemic therapy to concurrent CRT is widely used and accepted as an option to reduce these failures ,however selection of chemotherapy regimen and timing in relation to CRT is controversial. Doublet and triplet chemotherapy regimens using cisplatin and 5FU are throughly investigated in this setting.Inspite of significant improvement in disease free survival and overall survival they were poorly tolerated.Hence,minority of patients in the daily practice could tolerate those studied regimens as propsed. Recently, in multicenter randomized trial, Zhang and his group investigated gemcitabine and cisplatin as induction chemotherapy (ICT) added to CRT.It showed improvement in recurrence free survival and overall survival.More importantly 96.7% of the experimental arm completed the treatment protocol. This was further confirmed by an updated network of meta analysis by Bongiovanni et al.Again the question of "when" is still valid.Our proposal is to compare tolerable regimen in induction versus adjuvant settings.

Conditions

Nasopharyngeal Carcinoma

Keywords

Induction chemotherapy; neoadjuvant; adjuvant; non-metastatic; Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (4)

• Acute and late toxicity assessment

  Incidence of acute toxicity is calculated for each adverse event respectively, and severity evaluated on based of common terminology criteria for adverse event (CTCAE)

  3-5 years

• Late radiation toxicity

  assessed using the radiation therapy oncology group and Europe organization for research and treatment of cancer late radiation morbidity scoring scheme

  5-7 years

• Loco regional control rates (LCR)

  Defined as the time from the date of randomization to 1st failure in nasopharynx or neck lymph nodes

  3-5 years

• Progression free survival (PFS)

  Defined as the time from the date of randomization to 1st failure locally or systemically

  3-5 Years

Secondary Outcomes (2)

• Overall Survival (OS)

  5 years

• Distance Metastasis free survival (DMFS)

  5 years

Study Arms (2)

Induction Arm

EXPERIMENTAL

patients will receive three cycles of IC Gemcitabin/Cisplatin followed by radical CRT

Drug: Gemcitabin/cisplatin

Adjuvant Arm

ACTIVE COMPARATOR

Patients will receive radical CRT followed by three cycles of AC Gemcitabin/Cisplatin

Drug: Gemcitabin/cisplatin

Interventions

Gemcitabin/cisplatin DRUG

chemotherapy combination

Adjuvant Arm; Induction Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly histologically confirmed Nasopharyngeal carcinoma (according to World Health Organization (WHO) 2. The patient has stage III except T3N0 or IVA disease (according to 8th American Joint Committee on Cancer staging system) 3. WHO performance status 0-1 . 4. The patient must have achieved lawful age to provide informed consent according to local or national law .
• \. Laboratory values performed within 14 days prior to concurrent chemotherapy should be as follows: i) Absolute neutrophil count (ANC) ≥ 1500/mm ii) Platelet count ≥ 100.000/mm iii) Hemoglobin ≥ 8g/dl iv) Urea and serum creatinine ≤ 1.5 mg/dl. (for cisplatin) v) Creatinine clearance ≥ 60 ml/min. (for cisplatin) vi) SGOT and SGPT ≤ 2 × upper limit of laboratory normal 6. Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy

You may not qualify if:

• Age ≥70 or \<18
• The patient has evidence of distant metastatic disease.
• The patient has received prior systemic chemotherapy within the last three years.
• The patient has undergone previous surgery for the tumor, other than biopsy.
• The patient has received prior radiation therapy to the head or neck
• The patient is pregnant or breast feeding.
• The patient has a medical (e.g. renal impairment) or psychological condition that would not permit the patient to complete the trial or sign informed consent.
• Has known history of Human Immunodeficiency Virus (HIV)
• Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy,
• Has a history of severe hypersensitivity reaction to Cisplatin, Gemcitabine or radiotherapy or their analogs
• Unstable cardiac disease requiring treatment.

Sponsors & Collaborators

• Kuwait Cancer Control Center: lead

Study Sites (1)

Kuwait Cancer Control Center

Kuwait City, 11911, Kuwait

RECRUITING

Related Publications (8)

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Lee AW, Sze WM, Au JS, Leung SF, Leung TW, Chua DT, Zee BC, Law SC, Teo PM, Tung SY, Kwong DL, Lau WH. Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 2005 Mar 15;61(4):1107-16. doi: 10.1016/j.ijrobp.2004.07.702.

  PMID: 15752890 BACKGROUND

• Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. doi: 10.1200/JCO.1998.16.4.1310.

  PMID: 9552031 BACKGROUND

• Langendijk JA, Leemans CR, Buter J, Berkhof J, Slotman BJ. The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol. 2004 Nov 15;22(22):4604-12. doi: 10.1200/JCO.2004.10.074.

  PMID: 15542811 BACKGROUND

• Blanchard P, Lee A, Marguet S, Leclercq J, Ng WT, Ma J, Chan AT, Huang PY, Benhamou E, Zhu G, Chua DT, Chen Y, Mai HQ, Kwong DL, Cheah SL, Moon J, Tung Y, Chi KH, Fountzilas G, Zhang L, Hui EP, Lu TX, Bourhis J, Pignon JP; MAC-NPC Collaborative Group. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol. 2015 Jun;16(6):645-55. doi: 10.1016/S1470-2045(15)70126-9. Epub 2015 May 6.

  PMID: 25957714 BACKGROUND

• Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. doi: 10.1016/S1470-2045(11)70320-5. Epub 2011 Dec 7.

  PMID: 22154591 BACKGROUND

• Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.

  PMID: 31150573 BACKGROUND

• Lorch JH, Goloubeva O, Haddad RI, Cullen K, Sarlis N, Tishler R, Tan M, Fasciano J, Sammartino DE, Posner MR; TAX 324 Study Group. Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous-cell cancer of the head and neck: long-term results of the TAX 324 randomised phase 3 trial. Lancet Oncol. 2011 Feb;12(2):153-9. doi: 10.1016/S1470-2045(10)70279-5. Epub 2011 Jan 11.

  PMID: 21233014 BACKGROUND

Related Links

• Globocan.fr. Accessed January 2020.
• chemotherapy protocols

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Gemcitabine; Cisplatin

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)

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

Study Officials

• Shereen Issa, MD

  KCCC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mustafa Alsherify, MD

CONTACT

55466285; Mustafashawki@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Shereen Issa, MD

Model Details: Randomised controlled non-blinded

Study Record Dates

• First Submitted: May 13, 2021
• First Posted: May 24, 2021
• Study Start: May 1, 2021
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2026
• Last Updated: August 17, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

KU (1)