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)

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.

Target population: Patients with inoperable, locally advanced, or metastatic renal cell carcinoma.

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.

The master randomization list will be created, maintained and kept in a locked, secure location at Hospitalsapoteket Region Midtjylland, Afdeling Herning. The randomization list will not be available to any person directly involved in the study, including the study centre personnel or the project team.

Randomization will be performed via a central randomization service available in business hours on working days by fax 7843 5165. A block design randomization procedure will be used.