Oral ComplaintsPhase 3COMTTNCT01265810
Caphosol in Oral Mucositis Due to Targeted Therapy
A Phase 3 study testing supersaturated calcium-phosphate and sodium chloride 0.9 % in people with Oral Complaints and Renal Cell Carcinoma, run by Impaqtt Foundation at 2 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oral Complaints, Renal Cell Carcinoma, Hepatocellular Carcinoma
- What is being tested?
- supersaturated calcium-phosphate and sodium chloride 0.9 %
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 2 sitesNetherlands
- Study dates
- Nov 2011to Oct 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital
Amsterdam, 1066 CX
Leiden University Medical Centre (LUMC)
Leiden, 2300 RC
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
OM with mucosal change, associated pain, and taste change - are clinically relevant toxicities of TKI's and mTORI's presently in use. The incidence of oral mucositis of any grade is for sunitinib 38%, sorafenib 28%, pazopanib 4%, temsirolimus 41%, and for everolimus 44%.
Optimal antitumor activity requires maintaining the highest tolerable dose in individual patients. In order to improve health related quality of life (HRQoL) and patient adherence, adverse effects should be prevented, if possible avoided and treated if necessary. Current oral formulations consist of various schedules (continuous administration or 4 weeks on, 2 weeks off) to optimize the benefit-risk profile. Adherence to anti-cancer treatment is particularly important when prescribing oral therapies as adherence to the protocol can have a significant impact on efficacy and the severity of treatment-related AEs. As sorafenib, sunitinib, pazopanib, and everolimus are taken in the outpatient setting, patient education on the correct treatment dosing, usage and the nature, recognition, and severity of AEs is essential.
Recent data suggest that TKI and mTORI associated OM is different from conventional chemotherapy related OM. Oral ulceration usually presents as aphthous-like ulcerations and has in some studies been reported as mucositis. An analysis of the appearance, course, and toxicity experiences demonstrated that the condition is distinct from conventional mucositis and more closely resembles aphthous oral mucositis. These TKI/mTORI related ulcers may represent a dose-limiting toxicity for this new class of agents, especially considering the fact that even lower grade mucositis with chronic daily dosing may be cumbersome to the patient and lead to dose reductions. Studies of treatment strategies for aphthous OM may therefore be important for the dose adherence of TKI and mTORI and for the overall acceptance of this therapy for patients.
- Conditions
- Oral Complaints, Renal Cell Carcinoma, Hepatocellular Carcinoma, Gastrointestinal Stromal Tumors
- Being tested
- supersaturated calcium-phosphate, sodium chloride 0.9 %
- Keywords
- stomatitis, targeted therapy, Caphosol, mouthrinses
- Medical subject headings
- Carcinoma, Renal Cell, Carcinoma, Hepatocellular, Gastrointestinal Stromal Tumors, Stomatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
supersaturated calcium-phosphateOther
Also called Caphosol
4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days)
sodium chloride 0.9 %Other
4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days)
| Study group | Role | What they receive |
|---|---|---|
| sodium chloride -> supersaturated calcium-phosphate | Other | Patients in this arm start first with sodium chloride 0.9% mouth rinses and go crossover to supersaturated calcium-phosphate mouth rinses. Receives: Other: supersaturated calcium-phosphate; Other: sodium chloride 0.9 % |
| supersaturated calcium-phosphate -> sodium chloride | Other | Patients in this arm start first with supersaturated calcium-phosphate mouth rinses and go crossover to sodium chloride 0.9% mouth rinses. Receives: Other: supersaturated calcium-phosphate; Other: sodium chloride 0.9 % |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: once
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2010 (estimated)
- Study startNov 2011
- Primary completionAug 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Oral ComplaintsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Impaqtt Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- CB Boers ORG, Memorial Sloan Kettering Cancer Center, Leiden University Medical Center, Pfizer, Novartis, Jazz Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Christine B. Boers-Doets, MSc, Principal investigator, CB Boers ORGMario E Lacouture, MD, PhD, Principal investigator, Memorial Sloan Kettering Cancer CenterHans Gelderblom, MD, PhD, Study chair, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01265810
- Sponsor's protocol ID
- Impaqtt-002
- Acronym
- COMTT
- Status last verified
- Nov 2017
- First submitted
- 21 Dec 2010
- Last updated
- 13 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01265810
- Acronym / sponsor ID
- COMTT / Impaqtt-002
- Conditions
- Oral Complaints, Renal Cell Carcinoma, Hepatocellular Carcinoma, Gastrointestinal Stromal Tumors
- Keywords
- stomatitis, targeted therapy, Caphosol, mouthrinses
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Impaqtt FoundationUniversity, hospital or other
- Collaborators
- CB Boers ORG, Memorial Sloan Kettering Cancer Center, Leiden University Medical Center, Pfizer, Novartis, Jazz Pharmaceuticals
- Study start
- Nov 2011 (actual)
- Primary completion
- Aug 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 23 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OM with mucosal change, associated pain, and taste change - are clinically relevant toxicities of TKI's and mTORI's presently in use. The incidence of oral mucositis of any grade is for sunitinib 38%, sorafenib 28%, pazopanib 4%, temsirolimus 41%, and for everolimus 44%.
Optimal antitumor activity requires maintaining the highest tolerable dose in individual patients. In order to improve health related quality of life (HRQoL) and patient adherence, adverse effects should be prevented, if possible avoided and treated if necessary. Current oral formulations consist of various schedules (continuous administration or 4 weeks on, 2 weeks off) to optimize the benefit-risk profile. Adherence to anti-cancer treatment is particularly important when prescribing oral therapies as adherence to the protocol can have a significant impact on efficacy and the severity of treatment-related AEs. As sorafenib, sunitinib, pazopanib, and everolimus are taken in the outpatient setting, patient education on the correct treatment dosing, usage and the nature, recognition, and severity of AEs is essential.
Recent data suggest that TKI and mTORI associated OM is different from conventional chemotherapy related OM. Oral ulceration usually presents as aphthous-like ulcerations and has in some studies been reported as mucositis. An analysis of the appearance, course, and toxicity experiences demonstrated that the condition is distinct from conventional mucositis and more closely resembles aphthous oral mucositis. These TKI/mTORI related ulcers may represent a dose-limiting toxicity for this new class of agents, especially considering the fact that even lower grade mucositis with chronic daily dosing may be cumbersome to the patient and lead to dose reductions. Studies of treatment strategies for aphthous OM may therefore be important for the dose adherence of TKI and mTORI and for the overall acceptance of this therapy for patients.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sodium chloride -> supersaturated calcium-phosphate | Other | Other: supersaturated calcium-phosphate, Other: sodium chloride 0.9 %Patients 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 | Other | Other: supersaturated calcium-phosphate, Other: sodium chloride 0.9 %Patients in this arm start first with supersaturated calcium-phosphate mouth rinses and go crossover to sodium chloride 0.9% mouth rinses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| supersaturated calcium-phosphateAlso: Caphosol4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days) | Other | sodium chloride -> supersaturated calcium-phosphate, supersaturated calcium-phosphate -> sodium chloride |
| sodium chloride 0.9 %4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days) | Other | sodium chloride -> supersaturated calcium-phosphate, supersaturated calcium-phosphate -> sodium chloride |
Primary outcome
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%
Time frame: 2 times 14 days
4 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: once
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine B. Boers-Doets, MSc principal investigator
CB Boers ORG
Mario E Lacouture, MD, PhD principal investigator
Memorial Sloan Kettering Cancer Center
Hans Gelderblom, MD, PhD study chair
Leiden University Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing supersaturated calcium-phosphate and sodium chloride 0.9 % in people with Oral Complaints and Renal Cell Carcinoma, run by Impaqtt Foundation at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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% (time frame: 2 times 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.