Caphosol in Oral Mucositis Due to Targeted Therapy
COMTT
Phase III Randomized Double-blind Cross-over Trial of Caphosol® Versus NaCl 0.9% in the Relief of Oral Mucositis in Renal Cell Carcinoma, Hepatocellular Carcinoma, and Gastrointestinal Stromal Tumor Patients Receiving Targeted Therapy
1 other identifier
interventional
64
1 country
2
Brief Summary
Targeted therapies such as multi-targeted tyrosine kinase inhibitors (TKI) and mammalian target of rapamycin inhibitors (mTORI) in renal cell carcinoma (RCC), demonstrate a high level of efficacy with acceptable tolerability. Currently, there are five approved targeted therapies available for RCC: sunitinib (Sutent®), sorafenib (Nexavar®), pazopanib (Votrient®), temsirolimus (Torisel®), and everolimus (Afinitor®). Hepatocellular carcinoma treated with sorafenib and gastro intestinal stromal tumors patients treated with sunitinib will be included, too. Since this agents have dermatological adverse events in common, with oral mucositis (OM), hand-foot skin reaction (HFSR) and papulopustular eruption (PPE) as an disabling side effect, we require evidence based management options to prevent and treat these adverse events. The incidence of OM of any grade is for sunitinib 38%, sorafenib 28%, pazopanib 4%, temsirolimus 41%, and everolimus 44%. Recent data suggest that TKI and mTORI associated OM is distinct from conventional mucositis and more closely resembles aphthous OM. Recently, supersaturated calcium-phosphate rinse (Caphosol®), a Ca2+/PO43- mouth rinse, became available to prevent or treat OM. The objective is to assess the relieving effect of Caphosol® oral rinse on clinical outcomes which include oral intake, swallowing function and pain associated with incidence of grade ≥ 1 oral side effects and the anticancer therapy cessation in patients treated with selected targeted anticancer therapy. Patients with OM \> grade 0 on targeted therapy will be randomly allocated to receive either Caphosol® or NaCl 0.9% rinse for two weeks. After the first rinse period all patients will switch to the opposite treatment arm (NaCl 0.9% or Caphosol®) for another two weeks. Duration of oral side effects, severity, pain, dose of analgesics and tolerability will be assessed weekly with the Modified-VHNSS-version-2.0 oral-specific questionnaire. Patients will be stratified by targeted anticancer agent and per tumor type (pre-defined cohorts). Objective severity of oral side effects will be assessed using the NCI-CTCAE v4.0. Correlation of subjective Modified-VHNSS-version-2.0 scores with the objective NCI-CTCAE grade, sex, age, targeted therapy type, and cancer type will be conducted.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Nov 2011
Typical duration for phase_3
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 21, 2010
CompletedFirst Posted
Study publicly available on registry
December 23, 2010
CompletedStudy Start
First participant enrolled
November 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2015
CompletedNovember 13, 2017
November 1, 2017
3.8 years
December 21, 2010
November 8, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Assess the severity of patient-reported oral adverse events as determined by the change in the Modified-VHNSS2.0 score 3 times a week, from onset of oral adverse events during the active oral rinse period with Caphosol versus NaCl 0.9%
2 times 14 days
Secondary Outcomes (4)
Determine the decrease in grade of oral adverse events as measured by the NCI-CTCAE v4.0 once a week, during a 2 week treatment with Caphosol oral rinse versus NaCl 0.9% oral rinse, 4 times daily, 2 minutes with 30 ml solution
2 times 14 days
Assess the incidence of dose delay or dose interruption, dose reduction and discontinue treatment owing to oral burden due to targeted anticancer therapy during the active oral rinse period, once a week
2 times 14 days
To correlate the incidence of oral mucositis with: grade ≥ 2 hand-foot skin reaction (HFSR), and grade ≥ 2 papulopustular eruption (PPE) with all agents as measured by the NCI-CTCAE v4.0, during the active oral rinse period, once a week
2 times 14 days
Side Study: Explorative analysis of polymorphism in genes encoding for pharmacokinetic and pharmacodynamic variables related to the pharmacodynamics of the TKIs
once
Study Arms (2)
sodium chloride -> supersaturated calcium-phosphate
OTHERPatients in this arm start first with sodium chloride 0.9% mouth rinses and go crossover to supersaturated calcium-phosphate mouth rinses.
supersaturated calcium-phosphate -> sodium chloride
OTHERPatients in this arm start first with supersaturated calcium-phosphate mouth rinses and go crossover to sodium chloride 0.9% mouth rinses.
Interventions
4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days)
4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days)
Eligibility Criteria
You may qualify if:
- Male and female subjects
- ≥18 years of age
- Histological proof of RCC, HCC or GIST
- Oral adverse events \> grade 0 due to sunitinib, sorafenib, pazopanib, temsirolimus, or everolimus in mono therapy at study entry
- Written informed consent
- Eastern Co-operative Oncology Group (ECOG) performance status ≤ 2
- Able to perform oral rinsing
- Able to complete questionnaires by themselves or with assistance
You may not qualify if:
- Any previous systemic antineoplastic treatment within 4 weeks of initiation of current targeted anticancer therapy
- Current antineoplastic combination cytotoxic chemotherapy therapy
- Physiologic condition that precludes the use of an oral rinse
- Hypersensitivity to Caphosol ingredients
- Use of palifermin, oral cryotherapy, low level laser therapy, topical oral steroids within 3 weeks of current targeted anticancer therapy
- Oral abnormalities defined as baseline oral assessment of NCI-CTCAE v4.0 grade \> 0
- Current use of agents that are known to be strong inducers or inhibitors of CYP3A4 that can not be stopped
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Impaqtt Foundationlead
- CB Boers ORGcollaborator
- Memorial Sloan Kettering Cancer Centercollaborator
- Leiden University Medical Centercollaborator
- Pfizercollaborator
- Novartiscollaborator
- Jazz Pharmaceuticalscollaborator
Study Sites (2)
The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital
Amsterdam, 1066 CX, Netherlands
Leiden University Medical Centre (LUMC)
Leiden, 2300 RC, Netherlands
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christine B. Boers-Doets, MSc
CB Boers ORG
- PRINCIPAL INVESTIGATOR
Mario E Lacouture, MD, PhD
Memorial Sloan Kettering Cancer Center
- STUDY CHAIR
Hans Gelderblom, MD, PhD
Leiden University Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 21, 2010
First Posted
December 23, 2010
Study Start
November 1, 2011
Primary Completion
August 1, 2015
Study Completion
October 1, 2015
Last Updated
November 13, 2017
Record last verified: 2017-11