Trial record 4 of 6 for:    ((pazopanib AND GIST)OR Nct01391611 OR Nct01392352 OR NCT01339871 OR NCT01485042) | Open Studies

Caphosol in Oral Mucositis Due to Targeted Therapy (COMTT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Waterland Hospital
Sponsor:
Collaborators:
Leiden University Medical Center
EUSA Pharma (US), Inc.
Information provided by (Responsible Party):
Christine B Boers-Doets, Waterland Hospital
ClinicalTrials.gov Identifier:
NCT01265810
First received: December 21, 2010
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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 VHNSS 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 VHNSS scores with the objective NCI-CTCAE grade, sex, age, targeted therapy type, and cancer type will be conducted.


Condition Intervention Phase
Oral Mucositis
Renal Cell Carcinoma
Hepatocellular Carcinoma
Gastrointestinal Stromal Tumors
Other: supersaturated calcium-phosphate rinse
Other: sodium chloride 0.9 %
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Waterland Hospital:

Primary Outcome Measures:
  • Assess the severity of patient-reported oral adverse events as determined by the change in the 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Side Study: Explorative analysis of polymorphism in genes encoding for pharmacokinetic and pharmacodynamic variables related to the pharmacodynamics of the TKIs [ Time Frame: once ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: September 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: NaCl 0.9%
oral rinse
Other: sodium chloride 0.9 %
4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days)
Experimental: Caphosol
oral rinse
Other: supersaturated calcium-phosphate rinse
4 times daily, 2 minutes rinse with 30 ml solution during active rinse period (14 days)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01265810

Contacts
Contact: Christine B Boers-Doets, RN, MSc 0031-6-24790618 C.B.Boers-Doets@lumc.nl
Contact: Hans Gelderblom, MD, PhD 0031-71-5263486 A.J.Gelderblom@lumc.nl

Locations
Netherlands
The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: John BA Haanen, MD, PhD    0031-20-5122431    j.Haanen@nki.nl   
Contact: Henk Mallo, RN, MANP    0031-20-5122431    hmallo@nki.nl   
Principal Investigator: John Haanen, MD, PhD         
Leiden University Medical Centre (LUMC) Recruiting
Leiden, Netherlands, 2300 RC
Contact: Hans Gelderblom, PhD    0031-71-5263486    A.J.Gelderblom@lumc.nl   
Contact: Jan Ouwerkerk, RN    0031-71-5261965    J.Ouwerkerk@lumc.nl   
Principal Investigator: Hans Gelderblom, MD, PhD         
Sponsors and Collaborators
Christine B Boers-Doets
Leiden University Medical Center
EUSA Pharma (US), Inc.
Investigators
Study Chair: Christine B Boers-Doets, RN, MSc Waterland Hospital
Principal Investigator: Hans Gelderblom, MD, PhD Leiden University Medical Centre
Principal Investigator: Mario E Lacouture, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: Christine B Boers-Doets, MSc, RN, Waterland Hospital
ClinicalTrials.gov Identifier: NCT01265810     History of Changes
Other Study ID Numbers: Esperanz-002
Study First Received: December 21, 2010
Last Updated: June 11, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Waterland Hospital:
oral mucositis
targeted therapy
Caphosol
management

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Carcinoma, Hepatocellular
Carcinoma, Renal Cell
Mucositis
Stomatitis
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Gastroenteritis
Gastrointestinal Diseases
Mouth Diseases
Stomatognathic Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Gastrointestinal Neoplasms

ClinicalTrials.gov processed this record on October 19, 2014