Safety and Efficacy of Bis-Glyceryl Ascorbate (Amitose DGA) to Prevent Hand-Foot Skin Reaction in Patients With Renal Cell Carcinoma Receiving Sunitinib Therapy: Protocol for a Phase I/II, Uncontrolled, Single-Arm, Open-Label Trial (Preprint)

BACKGROUND Hand-foot skin reaction (HFSR) is a serious side effect induced by multiple-tyrosine kinase inhibitors (TKIs). HFSR can cause treatment interruption or decreased dosing. HFSR also markedly decreases quality of life and is associated with the therapeutic efficacy of multiple-TKIs. Therefore, the management and prevention of HFSR is an important issue; however, an effective method for its prevention has not been established. Specific ascorbic acid derivatives can reverse multiple-TKI-induced keratinocyte growth and pathological changes in vitro. OBJECTIVE This study was designed to evaluate the safety of bis-glyceryl ascorbate (Amitose DGA), a novel, hydrosoluble, and moisturizing ascorbic acid derivative, in patients with renal cell carcinoma (RCC) receiving sunitinib therapy. This study was also designed to evaluate Amitose DGA’s preventive efficacy for sunitinib-induced HFSR. METHODS This is a Phase I/II, single-center, uncontrolled, single-arm, open-label trial. We will recruit a total of 30 patients with RCC receiving sunitinib therapy, with a 2-week-on and 1-week-off schedule. The participants will apply Amitose DGA-containing cream over both palmar and plantar surfaces within two treatment cycles (ie, 6 weeks) of sunitinib in combination with a general moisturizing agent, in addition to standard-of-care processes. Safety assessments will include dermatological abnormalities, clinical laboratory tests, and incidence of adverse events. Efficacy assessments will include development of HFSR and therapeutic outcomes associated with sunitinib. RESULTS Recruitment to the study began in August 2017 and is ongoing in Japan. To date, 21 subjects have been recruited. Study completion is expected in 2021. CONCLUSIONS This is the first clinical study of Amitose DGA-containing cream in patients with RCC who are receiving sunitinib therapy. The single-center, single-arm, open-label design was selected to maximize subject exposure and increase the likelihood of achieving our study endpoints. The results will provide valuable and preliminary evidence of the effects of Amitose DGA-containing cream on HFSR. CLINICALTRIAL UMIN Clinical Trials Registry UMIN000027209; https://upload.umin.ac.jp/cgi-open-bin/ctr /ctr_view.cgi?recptno=R000031174 INTERNATIONAL REGISTERED REPOR DERR1-10.2196/14636

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Safety and Efficacy of Bis-Glyceryl Ascorbate (Amitose DGA) to Prevent Hand-Foot Skin Reaction in Patients With Renal Cell Carcinoma Receiving Sunitinib Therapy: Protocol for a Phase I/II, Uncontrolled, Single-Arm, Open-Label Trial

JMIR Research Protocols ◽

10.2196/14636 ◽

2019 ◽

Vol 8 (8) ◽

pp. e14636

Author(s):

Kazuhiro Yamamoto ◽

Takeshi Ioroi ◽

Kenichi Harada ◽

Satoshi Nishiyama ◽

Chikako Nishigori ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Ascorbic Acid ◽

Phase I ◽

Cell Carcinoma ◽

Skin Reaction ◽

Renal Cell ◽

Single Center ◽

Open Label ◽

Open Label Trial ◽

Hand Foot Skin Reaction

Background Hand-foot skin reaction (HFSR) is a serious side effect induced by multiple-tyrosine kinase inhibitors (TKIs). HFSR can cause treatment interruption or decreased dosing. HFSR also markedly decreases quality of life and is associated with the therapeutic efficacy of multiple-TKIs. Therefore, the management and prevention of HFSR is an important issue; however, an effective method for its prevention has not been established. Specific ascorbic acid derivatives can reverse multiple-TKI-induced keratinocyte growth and pathological changes in vitro. Objective This study was designed to evaluate the safety of bis-glyceryl ascorbate (Amitose DGA), a novel, hydrosoluble, and moisturizing ascorbic acid derivative, in patients with renal cell carcinoma (RCC) receiving sunitinib therapy. This study was also designed to evaluate Amitose DGA’s preventive efficacy for sunitinib-induced HFSR. Methods This is a Phase I/II, single-center, uncontrolled, single-arm, open-label trial. We will recruit a total of 30 patients with RCC receiving sunitinib therapy, with a 2-week-on and 1-week-off schedule. The participants will apply Amitose DGA-containing cream over both palmar and plantar surfaces within two treatment cycles (ie, 6 weeks) of sunitinib in combination with a general moisturizing agent, in addition to standard-of-care processes. Safety assessments will include dermatological abnormalities, clinical laboratory tests, and incidence of adverse events. Efficacy assessments will include development of HFSR and therapeutic outcomes associated with sunitinib. Results Recruitment to the study began in August 2017 and is ongoing in Japan. To date, 21 subjects have been recruited. Study completion is expected in 2021. Conclusions This is the first clinical study of Amitose DGA-containing cream in patients with RCC who are receiving sunitinib therapy. The single-center, single-arm, open-label design was selected to maximize subject exposure and increase the likelihood of achieving our study endpoints. The results will provide valuable and preliminary evidence of the effects of Amitose DGA-containing cream on HFSR. Trial Registration UMIN Clinical Trials Registry UMIN000027209; https://upload.umin.ac.jp/cgi-open-bin/ctr /ctr_view.cgi?recptno=R000031174 International Registered Report Identifier (IRRID) DERR1-10.2196/14636

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Abstract CT217: An open-label, Phase I/IIa study of VB10.NEO (DIRECT-01) in combination with checkpoint blockade in patients with locally advanced or metastatic solid tumors including melanoma, NSCLC, renal cell carcinoma, urothelial cancer or SSCHN

10.1158/1538-7445.sabcs18-ct217 ◽

2019 ◽

Author(s):

Jurgen Krauss ◽

Angela Krackhardt ◽

Elke Jager ◽

Anja Williams ◽

Hedda Wold ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Phase I ◽

Cell Carcinoma ◽

Solid Tumors ◽

Renal Cell ◽

Urothelial Cancer ◽

Locally Advanced ◽

Checkpoint Blockade ◽

Open Label ◽

Open Label Phase

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Targeted therapy and hand–foot skin reaction in advanced renal cell carcinoma

Expert Opinion on Drug Safety ◽

10.1517/14740331003596349 ◽

2010 ◽

Vol 9 (3) ◽

pp. 459-470 ◽

Cited By ~ 12

Author(s):

Chih-Hsun Yang ◽

Cheng-Keng Chuang ◽

Jia-Juan Hsieh ◽

John Wen-Cheng Chang

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Skin Reaction ◽

Renal Cell ◽

Advanced Renal Cell Carcinoma ◽

Hand Foot Skin Reaction

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A randomized multicenter phase II trial on efficacy of a hydrocolloid dressing containing ceramide with a low-friction external surface for hand-foot skin reaction caused by sorafenib in patients with renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9623 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9623-9623

Author(s):

Nobuo Shinohara ◽

Norio Nonomura ◽

Go Kimura ◽

Masatoshi Eto ◽

Hironobu Minami ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Skin Reaction ◽

Renal Cell ◽

External Surface ◽

Low Friction ◽

Hydrocolloid Dressing ◽

Dermatologic Toxicity ◽

Hand Foot Skin Reaction ◽

Soles Of The Feet

9623 Background: Hand-foot skin reaction (HFSR) is the most clinically significant and dose-limiting dermatologic toxicity in metastatic renal cell carcinoma (mRCC) patients who receive sorafenib (SOR). At present, evidence-based management strategy is not completely established. Since HFSR may be attributed to keratinous disorders of the skin and tends to develop in areas on the soles of the feet subject to strong pressure, a hydrocolloid dressing containing ceramide (a protective dressing against pressure ulcer) may prevent the development and worsening of HFSR. The purpose of the study is to investigate the usefulness of this material for HFSR on the soles of the feet in mRCC patients treated with SOR. Methods: Patients with grade 1 HFSR on the soles of the feet were randomly assigned 1:1 to receive a hydrocolloid dressing containing ceramide (Arm A) or 10% urea cream (Arm B). The detailed protocol of this study was presented in ASCO 2011 (Trial in Progress; TPS 233). A hydrocolloid dressing containing ceramide was applied to affected sites on the soles of the feet, but not to the hands. The primary endpoint was the incidence of Grade 2 or 3 HFSR on the soles of the feet in the first 4 weeks. Results: Thirty-three patients were evaluated; 17 patients in Arm A and 16 patients in Arm B. There were no significant differences in baseline characteristics between two arms. Over the 4 weeks period of this study, the incidence of Grade 2 or 3 HFSR on the soles of the feet was significantly lower in Arm A than Arm B; 5 (29%) patients in Arm A versus 11 (69%) in Arm B, p=0.03. On the other hand, the incidence of HFSR on the hands was similar between two arms. The median time to Grade 2 or 3 HFSR on the soles of the feet was significant longer in Arm A compared with Arm B; not reach (95%CI 13-28+) in Arm A versus 22 days (95%CI 15-27), p=0.03. Regarding the pain levels on the soles, Arm A was superior to Arm B (p=0.05). Conclusions: These results indicate that a hydrocolloid dressing containing ceramide with a low-friction external surface is effective in preventing the worsening of HFSR caused by SOR in mRCC patients. Clinical trial information: UMIN000002016.

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