RUBRACA- rucaparib camsylate tablet, film coated
Clovis Oncology, Inc.
1 INDICATIONS AND USAGE
1.1 Maintenance Treatment of BRCA -mutated Recurrent Ovarian Cancer
Rubraca is indicated for the maintenance treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)- associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
1.2 BRCA -mutated Metastatic Castration-Resistant Prostate Cancer
Rubraca is indicated for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Rubraca [see Dosage and Administration (2.1)].
This indication is approved under accelerated approval based on objective response rate and duration of response [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
Maintenance Treatment of BRCA -mutated Recurrent Ovarian Cancer
Select patients for the maintenance treatment of recurrent ovarian cancer with Rubraca based on the presence of a deleterious BRCA mutation (germline and/or somatic) [see Clinical Studies (14.1) ].
An FDA-approved test for the detection of deleterious germline and/or somatic BRCA mutations is not currently available.
Treatment of BRCA -mutated mCRPC after Androgen Receptor-directed Therapy and Chemotherapy
Select patients for the treatment of mCRPC with Rubraca based on the presence of a deleterious BRCA mutation (germline and/or somatic) in plasma specimens [see Clinical Studies (14.2)]. A negative result from a plasma specimen does not mean that the patient’s tumor is negative for BRCA mutations. Should the plasma specimen have a negative result, consider performing further genomic testing using tumor specimens as clinically indicated.
Information on the FDA-approved tests for the detection of a BRCA mutation in patients with ovarian cancer or with prostate cancer is available at: http://www.fda.gov/CompanionDiagnostics.
2.2 Recommended Dose
The recommended dose of Rubraca is 600 mg (two 300 mg tablets) taken orally twice daily with or without food, for a total daily dose of 1,200 mg.
Continue treatment until disease progression or unacceptable toxicity.
If a patient misses a dose of Rubraca, instruct the patient to take the next dose at its scheduled time. Vomited doses should not be replaced.
Patients receiving Rubraca for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
2.3 Dose Modifications for Adverse Reactions
To manage adverse reactions, consider interruption of treatment or dose reduction. Recommended Rubraca dose modifications for adverse reactions are indicated in Table 1.
|Starting Dose||600 mg twice daily (two 300 mg tablets)|
|First Dose Reduction||500 mg twice daily (two 250 mg tablets)|
|Second Dose Reduction||400 mg twice daily (two 200 mg tablets)|
|Third Dose Reduction||300 mg twice daily (one 300 mg tablet)|
3 DOSAGE FORMS AND STRENGTHS
- Tablets (200 mg): blue, round, immediate-release, film-coated, debossed with “C2”.
- Tablets (250 mg): white, diamond, immediate-release, film-coated, debossed with “C25”.
- Tablets (300 mg): yellow, oval, immediate-release, film-coated, debossed with “C3”.
5 WARNINGS AND PRECAUTIONS
5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur in patients treated with Rubraca, and are potentially fatal adverse reactions. In 1594 treated patients with ovarian cancer [see Adverse Reactions (6.1)] , MDS/AML occurred in 32 patients (2%), including those in long term follow-up. Of these, 14 occurred during treatment or during the 28-day safety follow-up (0.9%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from < 2 months to approximately 72 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing chemotherapy regimens and/or other DNA damaging agents.
In ARIEL3, of patients with a germline and/or somatic BRCA mutation treated with Rubraca, MDS/AML occurred in 9 out of 129 (7%) patients treated with Rubraca and 4 out of 66 (6%) patients treated with placebo. The duration of therapy with Rubraca in patients who developed secondary MDS/cancer therapy-related AML varied from 1.2 to 4.7 years.
In TRITON2, MDS/AML was not observed in patients with mCRPC (n=209) regardless of homologous recombination deficiency (HRD) mutation [see Adverse Reactions (6.1)].
Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1). Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose according to Table 1 [see Dosage and Administration (2.3)] and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.
5.2 Embryo-Fetal Toxicity
Rubraca can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings from animal studies. In an animal reproduction study, administration of rucaparib to pregnant rats during the period of organogenesis resulted in embryo-fetal death at exposures that were 0.04 times the AUC0-24h in patients receiving the recommended human dose of 600 mg twice daily. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
Based on findings from genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of Rubraca [see Use in Specific Populations (8.1, 8.3)].
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