U.S. flag An official website of the United States government
  1. Home
  2. Drugs
  3. Development & Approval Process | Drugs
  4. Drug Approvals and Databases
  5. Drug Trials Snapshot: RUBRACA
  1. Drug Approvals and Databases

Drug Trials Snapshot: RUBRACA

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to RUBRACA Prescribing Information for complete information.

RUBRACA (rucaparib)
roo-brah’-kah
Clovis Oncology, Inc.
Approval date: December 19, 2016


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

RUBRACA is a drug used to treat women with advanced ovarian cancer who:

  • have certain BRCA gene mutation (either inherited or acquired), and
  • have received previous treatment with 2 or more chemotherapy medicines for their cancer.

How is this drug used?

Two tablets (total of 600 mg) are taken two times a day with or without food.

What are the benefits of this drug?

Fifty-four percent of 106 women who were treated with RUBRACA experienced complete or partial shrinkage of their tumors lasting on an average 9.2 months.

More trials are ongoing to confirm the clinical benefit of RUBRACA.

What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results for the clinical trials based on the efficacy population. Objective response rate (ORR) and duration of response (DOR) were assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and were supported by independent radiology review.

Table 2. Overall Response and Duration of Response in Patients with BRCA-mutant Ovarian Cancer Who Received Two or More Chemotherapies in Trial 1 and Trial 2

  Investigator-assessed
N=106
Objective Response Rate (95% CI) 54% (44, 64)
Complete Response 9%
Partial Response 45%
Median DOR in months (95% CI) 9.2 (6.6 ,11.6)

RUBRACA Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

The disease occurs only in women, therefore only race and age differences were analyzed.

  • Race: The majority of patients in the clinical trials were White. Differences in response to RUBRACA among races could not be determined.
  • Age: The number of participants above 65 years of age was limited; therefore, differences in response between patients above and below 65 years of age could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes efficacy results of Objective Response Rate (ORR) and median Duration of Response (DOR) in months by age and racial subgroup.

Table 3. Subgroup Analysis of Objective Response Rate (ORR) and Median Duration of Response (DOR) As Assessed by the Investigator

 

ORR
n %
(95% CI)
Median DOR
(95% CI)

Age Group

  <65 years="" (n="">

35 (51.5)
(39, 63.8)
8.9
(5.5,11.7)

  ≥65 years (n=38)

22 (57.9)
(40.8,73.7)
9.7
(6.6, NR)

Race

White (n=83)

46 (55.4)
(44.1, 66.3)
9.7
(5.7, 12.9)

   Non-White (n=13)

6 (46.2)
(19.2, 74.9)
7.6
(4.4, NR)

   Unknown (10)

5 (50)
(18.7, 81.3)
NR
(9.2, NR)

NR = Not Reached
Adapted from FDA Statistical review

What are the possible side effects?

The most common side effects of RUBRACA are nausea, tiredness, vomiting, low red cell count in the blood (anemia), stomach-area pain, unusual taste sensation, constipation, decreased appetite, diarrhea, low platelet count in the blood, and shortness of breath.

RUBRACA may cause serious side effects including a bone marrow disorder (myelodysplastic syndrome) and leukemia and may harm an unborn baby.

What are the possible side effects (results of trials used to assess safety)?

The tables below summarize adverse reactions and electrolyte abnormalities in the combined clinical trials (safety population).

Table 4. Adverse Reactions reported in ≥ 20% of Patients with Ovarian Cancer Treated with RUBRACA 600mg Twice Daily

Adverse Reaction All Ovarian Cancer Patients
(N = 377)

%
Grades a 1-4 Grades 3-4
Gastrointestinal Disorders
Nausea 77 5
Vomiting 46 4
Constipation 40 2
Diarrhea 34 2
Abdominal Pain 32 3
General Disorders
Asthenia/Fatigue 77 11
Blood and Lymphatic System Disorders
Anemia 44 25
Thrombocytopenia 21 5
Nervous System Disorders
Dysgeusia 39 0.3
Metabolism and Nutrition Disorders
Decreased appetite 39 3
Respiratory, Thoracic, and Mediastinal Disorders
Dyspnea 21 0.5

aNational Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03)
RUBRACA Prescribing Information

Table 5. Laboratory Abnormalities Reported in ≥ 35% of Patients with Ovarian Cancer Treated with RUBRACA 600 mg Twice Daily

Laboratory Parameter All Patients with Ovarian Cancer
(N = 377)

%
Grade 1-4 a Grade 3-4
Clinical Chemistry
Increase in creatinine 92 1
Increase in ALTb 74 13
Increase in ASTb 73 5
Increase in cholesterol 40 2
Hematologic
Decrease in hemoglobin 67 23
Decrease in lymphocytes 45 7
Decrease in platelets 39 6
Decrease in absolute neutrophil count 35 10

aAt least one worsening shift in CTCAE grade and by maximum shift from baseline.
bIncrease in ALT/AST led to treatment discontinuation in 0.3% of patients (1/377).
RUBRACA Prescribing Information

Were there any differences in side effects among sex, race and age?

Were there any differences in side effects among sex, race, and age?
The disease occurs only in women, therefore only race and age differences were analyzed.

  • Race:  The majority patients in the clinical trials were White. Differences in side effects among races could not be determined.
  • Age: The occurrence of side effect was similar between patients below and above 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes treatment emergent adverse events (TEAEs) during the clinical trials by race and age subgroup.

Table 6. Subgroup Analysis of Treatment-Emergent Adverse Events by Race (N=339)*

  RUBRACA
Non-White
(N=37)
White
(N=302)
TEAEa 37 (100%) 302 (100%)
Serious TEAEa 13 (35.1) 83 (27.4%)
≥ Grade 3 TEAEa 24 (64.9) 182 (60.1%)

*38 (10%) of patients had race missing
aincluded events of disease progression
TEAE=Treatment Emergent Adverse Event
FDA Clinical review

Table 7. Subgroup Analysis of Treatment-Emergent Adverse Events by Age (N=377)

   RUBRACA
     Age < 65="">
N = 217
     Age ≥65 to <75 >
           N = 119
    Age ≥75 Years
         N = 41
   Age ≥65  Years
        N = 160
TEAEa             217 (100%)            119 (100%)           41 (100%)         160 (100%)
Serious TEAEa               59 (27.2%)              36 (30.3%)             9 (22%)           45 (28.1%)
≥ Grade 3 TEAEa             125 (57.6%)              78 (65.5%)           26 (63.4%)          104 (65%)

aincluded events of disease progression
FDA Clinical review

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The benefit of RUBRACA was evaluated based on evidence from 106 patients with advanced ovarian cancer enrolled in two clinical trials of. These patients form the efficacy population and will be presented in the Figures 1a-3a below.

The safety of RUBRACA (side effects) was evaluated on a population from the same two trials and one additional trial. All of these patients together (total of 377) form the safety population and will be presented in Figures 1b-3b below.

The trials were conducted in the USA, Canada, Australia, Europe, and Israel.

Figures 1a and 1b summarize how many women were in the clinical trials used to evaluate the benefits and side effects of RUBRACA.

Figure 1a. Baseline Demographics by Sex (efficacy population)

how many women participated in the clinical trials of the drug RUBRACA. In total, 106 women (100%) participated in the clinical trials used to evaluate efficacy.)

Clinical trial data

Figure 1b. Baseline Demographics by Sex (safety population)

how many women participated in the clinical trial of the drug RUBRACA. In total, 377 women (100%) participated in the clinical trials used to evaluate drug safety.)

Clinical trial data

Figure 2a and Table 2a below summarize the percentage of patients by race in the clinical trials used to evaluate the benefits of RUBRACA.

Figure 2a. Baseline Demographics by Race (efficacy population)

percentage of patients by race in the RUBRACA clinical trials. In total, 83 Whites (78%), 4 Blacks (4%), 7 Asians (7%), 2 Other (2%) and for 10 participants (9%) race was missing.

Clinical trial data

Table 1a. Baseline Demographics by Race (efficacy population)

Race Number of Patients               Percentage
White 83 78
Black or African American 4 4
Asian 7 7
Other 2 2
Missing 10 9

Clinical trial data

Figure 2b and Table 2b below summarize the percentage of patients by race in the clinical trials used to evaluate the side effects of RUBRACA.

Figure 2b. Baseline Demographics by Race (safety population)

percentage of patients by race in the RUBRACA clinical trials. In total, 302 Whites (80%), 8 Blacks (2%), 22 Asians (6%), 7 all Others combined (2%) and for 38 patients (10%) race was missing.

*includes American Indian or Alaska Native, Multiple and Other
Clinical trial data

Table 1b. Baseline Demographics by Race (safety population)

Race Number of Patients Percentage
White 302 80%
Black or African American 8 2%
Asian 22 6%
American Indian or Alaska Native 1 less than %
Multiple 2 1%
Other 4 1
Missing 38 10%

Clinical trial data

Figures 3a and 3b below summarize the percentage of patients by age in the clinical trials used to evaluate the benefits and side effects of RUBRACA.

Figure 3a. Baseline Demographics by Age (efficacy population)

how many individuals of certain age groups were in the RUBRACA clinical trials.  In total, 68 patients were less than 65 years old (63%) and  and 38 were  65 and older (37%).

Clinical trial data

Figure 3b. Baseline Demographics by Age (safety population)

how many individuals of certain age groups were in the RUBRACA clinical trials.  In total, 217 patients  were less than  65 years old (57%), 119 patients were 65 to 75 years old (32%) and 41 were  75 years and older (11%).

Clinical trial data

Who participated in the trials?

The table below summarizes demographics of patients in the clinical trials based on the efficacy population.

Table 8. Baseline Demographics of Patients in the Clinical Trials (efficacy population)

Demographic Parameters RUBRACA N
=106

n (%)
Sex
    Women 106 (100)
Age
   Median (Range) 59 (33-84)
Age Group
<65> 68 (63)
≥65 years 38 (37)
Race
White 83 (78%)
Asian 7 (7%)
Black of African American 4 (4)
Other 2 (2)
Missing 10 (9)
Region
US 26 (25)
Australia 4 (4)
Europe 31 (29)
Canada 31 (29)
Israel 14 (13)

Clinical trial data

The table below summarizes demographics of patients in the clinical trials based on the safety population.

Table 9. Baseline Demographics of Patients in the Clinical Trials (safety population)

Demographic Parameters RUBRACA
N=377

n (%)
Sex
    Women 377 (100)
Age
   Median (Range)  62 (31-86)
Age Group
<65>   217 (58)
65-75 years    119 (32)
≥75 years    41 (11)
Race
White   302 (80%)
Asian   22 (6%)
Black of African American     8 (2)
American Indian or Alaska Native     1 (<>
Other     4 (1)
Multiple     2 (1)
Missing   38 ( 10)
Ethnicity
Non-Hispanic or Latino 317 (84)
Hispanic or Latino    13 (3)
Not reported 43 (11)
Missing   4 (1)
Region
US 142 (38)
Europe 120 (32)
Canada   83 (22)
Other   32 (8)

Clinical trial data

How were the trials designed?

The benefit and side effects of RUBRACA were evaluated in two clinical trials of patients with advanced ovarian cancer. All patients received RUBRACA twice a day until either the disease worsened or the patients developed an unacceptable side effect.

The benefit of RUBRACA was evaluated by measuring the proportion of patients whose tumor size decreased by at least 30% during treatment and by how long that response lasted.

How were the trials designed?

There were two single-arm, open-label, multicenter clinical trials. Patients in the efficacy population had advanced BRCA-mutant ovarian cancer and had progressed after 2 or more prior chemotherapies. All patients received RUBRACA twice daily as monotherapy until disease progression or unacceptable toxicity.

The efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) assessed by the investigator and supported by independent radiology review according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

Back to Drug Trials Snapshots