Folic Acid Supplement Versus Placebo for Treating Mucositis Adverse Events in Metastatic Renal Cell Carcinoma Patients Receiving Targeted Therapy

Study Overview
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Brief Summary
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FASTERCC: Folic acid supplement versus placebo for treating mucositis adverse events in metastatic renal cell carcinoma patients receiving targeted therapy. A randomized, double-blind trial from the Danish renal cancer group (DARENCA study-4)

Detailed Description
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Mucositis (nasal, oral, pharyngeal, anal, or genital) is often experienced in relation to TKI, immunotherapy or mTOR inhibitor treatment in mRCC patients. The present trial will assess whether 12 weeks complementary treatment with folic acid in mRCC-patients receiving TKI- or mTOR inhibitor treatment or immunotherapy and displaying CTCAE mucositis grade ≥2 can reduce the degree of mucositis, compared to PLACEBO. This is a randomized, double-blind, placebo-controlled phase II trial of the effectiveness of folic acid supplement for 12 weeks on mucositis. Both arms will receive best supportive care. No crossover is allowed. The investigators anticipate a 24-month accrual period. The power calculation indicates a total of 50 patients per group are required. Block randomization based on received TKI/ mTOR inhibitor/IT-treatment will be performed.

Official Title
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FASTERCC: Folic Acid Supplement Versus Placebo for Treating Mucositis Adverse Events in Metastatic Renal Cell Carcinoma Patients Receiving Targeted Therapy. A Randomized, Double-blind Trial From the Danish Renal Cancer Group (DARENCA Study-4)

Conditions
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Mucositis

Intervention / Treatment
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* Drug: Folic Acid
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Target population: Patients with inoperable, locally advanced, or metastatic renal cell carcinoma. Inclusion Criteria: Patients displaying CTCAE ≥2 mucositis during TKI, mTOR inhibitor or immunotherapy treatment. Signed written informed consent obtained prior to any study specific procedures. Patient must be willing and able to comply with the protocol. Age ≥ 18. Biopsy proven locally advanced or metastatic renal cell carcinoma. Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded (postmenopausal, hysterectomy or oophorectomy) and not lactating. Fertile women of childbearing potential (<2 years after last menstruation) and men must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgical sterilization). Karnofsky Performance status ≥ 60%. Exclusion Criteria: Known hypersensitivity to folic acid. Use of prednisolone more than 10 mg daily.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled phase II trial of the effectiveness of folic acid supplement for 12 weeks on mucositis. Both arms will receive best supportive care. No crossover is allowed.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment arm<br>5 mg of folic acid (1 tablet) per day for 12 weeks. | Drug: Folic Acid<br>* 5 mg pr day for 12 weeks<br>|
| Placebo Comparator: Placebo arm<br>PLACEBO (1 tablet) per day for 12 weeks. | Drug: Placebo Oral Tablet<br>* 1 placebo pill pr day for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CTCAE Mucositis | The degree of CTCAE mucositis (nasal, oral, pharyngeal, anal, or genital) according to the Common Terminology Criteria for Adverse Events v. 4.0 (CTCAE). | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRO Mucositis frequency | The frequency of mucositis (nasal, oral, pharyngeal, anal, or genital) according to patient reported outcomes (PRO) by self assessment questionnaire using National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (NCCN-FACT FKSI-19) and a modified version of the M.D. Anderson Symptom Inventory (MDASI) for RCC. | 16 weeks | 
| Time to effect on mucositis | The median time to effect of study drug according to CTCAE 4.0 and PRO. | 16 weeks | 
| Dose reductions | The frequency of TKI/mTOR dose reductions in the two groups | 16 weeks | 
| Treatment discontinuations | The frequency of TKI/mTOR/immunotherapy treatment discontinuations in the two groups | 16 weeks | 
| Treatment withdrawals | The frequency of TKI/mTOR/immunotherapy treatment withdrawals in the two groups | 16 weeks | 
| GI adverse events degree | The degree of GI adverse events in the two groups according to CTCAE v. 4.0 and PRO. | 16 weeks | 
| Hand-foot syndrome degree | The degree of hand-foot syndrome in the two groups according to CTCAE v. 4.0 and PRO. | 16 weeks | 
| QOL NCCN | The quality of life in the two groups according to NCCN-FACT FKSI-19. | 16 weeks | 
| PRO Mucositis degree | The degree of mucositis (nasal, oral, pharyngeal, anal, or genital) according to patient reported outcomes (PRO) by self assessment questionnaire using National Comprehensive Cancer Network Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (NCCN-FACT FKSI-19) and a modified version of the M.D. Anderson Symptom Inventory (MDASI) for RCC. | 16 weeks | 
| GI adverse events frequency | The frequency of GI adverse events in the two groups according to CTCAE v. 4.0 and PRO. | 16 weeks | 
| Hand-foot syndrome frequency | The frequency of hand-foot syndrome in the two groups according to CTCAE v. 4.0 and PRO. | 16 weeks | 
| QOL MDASI | The quality of life in the two groups according the M.D. Anderson Symptom Inventory for RCC. | 16 weeks |