Parotid-gland Stem-cell Sparing Intensity-modulated Radiotherapy

NCT01955239 | Completed DMC

• 1 other identifier: RT2011-04
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Radiation-induced parotid gland dysfunction, often leading to xerostomia is the most-frequently occurring side-effect with a major impact on patient-reported quality of life after radiotherapy for head and neck cancer (HNC). Therefore, treatments for HNC are currently optimized to minimize the mean dose to the parotid glands. Though this resulted in a significant reduction of toxicity, 30%-40% of the patients still develop sustained parotid gland dysfunction and xerostomia. However, in animal studies the investigators found that the dose to the sub-volume of the gland containing the parotid gland stem cells is a better predictor for dysfunction than the mean dose to the whole gland. Subsequently, this finding was confirmed in a retrospective analysis in patients. Therefore, a reduction of dose specifically in this sub-volume of the parotid glands of patients is expected to further reduce the risk of parotid gland dysfunction and xerostomia. Objective: To test the hypothesis that parotid gland stem cell sparing intensity modulated radiotherapy in HNC patients reduces the risk of parotid gland dysfunction and xerostomia as compared to conventional parotid gland sparing intensity modulated radiotherapy. Study design: Double-blind prospective randomized trial (51 patients per arm). Study population: Patients treated for tumours in the head-and-neck region with curative radiotherapy, with or without the addition of chemotherapy or cetuximab. Intervention: Patients randomized into the experimental arm will receive a treatment in which the radiation dose to the parotid gland is re-distributed to minimize dose to the sub-volume containing the stem cells, while keeping the same mean dose to the parotid gland as a whole. Main study parameters/endpoints: Primary endpoint is parotid gland salivary secretion. Secondary endpoints are patient- and physician-rated xerostomia.

Conditions

Head and Neck Cancer

Keywords

Head and Neck Cancer; Radiotherapy; IMRT; Stem cell; Parotid gland

Outcome Measures

Primary Outcomes (1)

• Salivary flow

  12 months after radiotherapy

Secondary Outcomes (1)

• Patient-rated Xerostomia

  12 months after radiotherapy

Study Arms (2)

Standard IMRT

ACTIVE COMPARATOR

Standard IMRT in which the mean dose to both whole parotid glands is minimized.

Radiation: Intensity-modulated Radiotherapy

Stem-cell Sparing IMRT

EXPERIMENTAL

Stem-cell Sparing IMRT in which the mean dose to the stem cell containing region of the parotid gland is minimized

Radiation: Intensity-modulated Radiotherapy

Interventions

Intensity-modulated Radiotherapy RADIATION

Standard IMRT; Stem-cell Sparing IMRT

Eligibility Criteria

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

You may qualify if:

• Squamous cell carcinoma originating from the mucosa of the head and neck area or nasopharyngeal carcinoma originating from the nasopharynx;
• The radiotherapy includes prophylactic or therapeutic irradiation of both sides of the neck (at least level II to IV);
• Age ≥ 18 years;
• WHO performance 0-2;
• To reduce the uncertainty in the assessment of relative flow after treatment, pre-treatment parotid gland saliva production stimulated with 5% citric acid should exceed \>0.1 ml/min

You may not qualify if:

• Postoperative radiotherapy;
• Previous radiotherapy of the head and neck region (re-irradiation);
• Unilateral radiotherapy;
• Primary salivary gland tumours

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9700RB, Netherlands

Location

Related Publications (8)

• Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, Slotman BJ. Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol. 2008 Aug 1;26(22):3770-6. doi: 10.1200/JCO.2007.14.6647.

  PMID: 18669465 BACKGROUND

• Beetz I, Schilstra C, van der Schaaf A, van den Heuvel ER, Doornaert P, van Luijk P, Vissink A, van der Laan BF, Leemans CR, Bijl HP, Christianen ME, Steenbakkers RJ, Langendijk JA. NTCP models for patient-rated xerostomia and sticky saliva after treatment with intensity modulated radiotherapy for head and neck cancer: the role of dosimetric and clinical factors. Radiother Oncol. 2012 Oct;105(1):101-6. doi: 10.1016/j.radonc.2012.03.004. Epub 2012 Apr 18.

  PMID: 22516776 BACKGROUND

• Eisbruch A. Radiotherapy: IMRT reduces xerostomia and potentially improves QoL. Nat Rev Clin Oncol. 2009 Oct;6(10):567-8. doi: 10.1038/nrclinonc.2009.143. No abstract available.

  PMID: 19787001 BACKGROUND

• Konings AW, Cotteleer F, Faber H, van Luijk P, Meertens H, Coppes RP. Volume effects and region-dependent radiosensitivity of the parotid gland. Int J Radiat Oncol Biol Phys. 2005 Jul 15;62(4):1090-5. doi: 10.1016/j.ijrobp.2004.12.035.

  PMID: 15990013 BACKGROUND

• Konings AW, Faber H, Cotteleer F, Vissink A, Coppes RP. Secondary radiation damage as the main cause for unexpected volume effects: a histopathologic study of the parotid gland. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):98-105. doi: 10.1016/j.ijrobp.2005.06.042. Epub 2005 Oct 13.

  PMID: 16226398 BACKGROUND

• Lombaert IM, Brunsting JF, Wierenga PK, Faber H, Stokman MA, Kok T, Visser WH, Kampinga HH, de Haan G, Coppes RP. Rescue of salivary gland function after stem cell transplantation in irradiated glands. PLoS One. 2008 Apr 30;3(4):e2063. doi: 10.1371/journal.pone.0002063.

  PMID: 18446241 BACKGROUND

• Lombaert IM, Brunsting JF, Wierenga PK, Kampinga HH, de Haan G, Coppes RP. Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool. Stem Cells. 2008 Oct;26(10):2595-601. doi: 10.1634/stemcells.2007-1034. Epub 2008 Jul 31.

  PMID: 18669914 BACKGROUND

• Doornaert P, Dahele M, Ljumanovic R, de Bree R, Slotman BJ, Castelijns JA. Use of diffusion-weighted magnetic resonance imaging (DW-MRI) to investigate the effect of chemoradiotherapy on the salivary glands. Acta Oncol. 2015 Jul;54(7):1068-71. doi: 10.3109/0284186X.2014.987357. Epub 2014 Dec 18. No abstract available.

  PMID: 25519706 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: October 7, 2013
• Study Start: September 1, 2013
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: June 22, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)