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

Phase 2

Recruiting

• Conditions: Mucositis; Stomatitis
• Interventions: Drug: Folic Acid; Drug: Placebo Oral Tablet

• Registration Number: NCT03581773
• Lead Sponsor: Niels Fristrup

Brief Summary

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

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 96-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.

Study Timeline

• Study Start: 2017-12-20
• Study First Submitted: 2018-05-07
• Study First Submitted QC: 2018-07-09
• Study First Posted: 2018-07-10
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-28
• Last Update Posted: 2025-03-05
• Primary Completion: 2026-12-20
• Study Completion: 2028-12-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Patients displaying CTCAE ≥2 mucositis during TKI, mTOR inhibitor or immunotherapy treatment.
2. Signed written informed consent obtained prior to any study specific procedures.
3. Patient must be willing and able to comply with the protocol.
4. Age ≥ 18.
5. Biopsy proven locally advanced or metastatic renal cell carcinoma.
6. Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded (postmenopausal, hysterectomy or oophorectomy) and not lactating.
7. 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).
8. Karnofsky Performance status ≥ 60%.

Exclusion Criteria

1. Known hypersensitivity to folic acid.
2. Use of prednisolone more than 10 mg daily.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment arm	Folic Acid	5 mg of folic acid (1 tablet) per day for 12 weeks.
Placebo arm	Placebo Oral Tablet	PLACEBO (1 tablet) per day for 12 weeks.

Primary Outcome Measures

Name	Time	Method
CTCAE Mucositis	16 weeks	The degree of CTCAE mucositis (nasal, oral, pharyngeal, anal, or genital) according to the Common Terminology Criteria for Adverse Events v. 4.0 (CTCAE).

Secondary Outcome Measures

Name	Time	Method
PRO Mucositis frequency	16 weeks	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.
Time to effect on mucositis	16 weeks	The median time to effect of study drug according to CTCAE 4.0 and PRO.
Dose reductions	16 weeks	The frequency of TKI/mTOR dose reductions in the two groups
Treatment discontinuations	16 weeks	The frequency of TKI/mTOR/immunotherapy treatment discontinuations in the two groups
Treatment withdrawals	16 weeks	The frequency of TKI/mTOR/immunotherapy treatment withdrawals in the two groups
GI adverse events degree	16 weeks	The degree of GI adverse events in the two groups according to CTCAE v. 4.0 and PRO.
Hand-foot syndrome degree	16 weeks	The degree of hand-foot syndrome in the two groups according to CTCAE v. 4.0 and PRO.
QOL NCCN	16 weeks	The quality of life in the two groups according to NCCN-FACT FKSI-19.
PRO Mucositis degree	16 weeks	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.
GI adverse events frequency	16 weeks	The frequency of GI adverse events in the two groups according to CTCAE v. 4.0 and PRO.
Hand-foot syndrome frequency	16 weeks	The frequency of hand-foot syndrome in the two groups according to CTCAE v. 4.0 and PRO.
QOL MDASI	16 weeks	The quality of life in the two groups according the M.D. Anderson Symptom Inventory for RCC.

Trial Locations

Locations (2)

Aarhus University Hospital, Department of oncology; 🇩🇰 Aarhus, Central Region Of Denmark, Denmark

Department of Oncology, Herlev Hospital; 🇩🇰 Herlev, Denmark