Rucaparib Clinical Trials

What Is Rucaparib?

Rucaparib is a chemotherapy medication that functions as a poly (ADP-ribose) polymerase, or PARP inhibitor. This type of drug works by interfering with the ability of cancer cells to repair damaged DNA, leading to cell death. By targeting these DNA repair pathways, Rucaparib aims to selectively harm cancer cells while minimizing damage to healthy cells. This mechanism makes Rucaparib a targeted therapy that focuses on the DNA damage response (DDR) pathways within cancer cells.

Currently, Rucaparib is being investigated in clinical trials for its potential to treat various cancers. The drug has been studied in 62 trials involving a total of 12,968 participants since the first trial began on April 23, 2008. The latest trial started on April 1, 2021, with 2 trials currently recruiting new participants and 36 trials already completed.

Uses and Conditions Under Study

Rucaparib is being studied for its effectiveness in treating a variety of cancers, often focusing on its role as a PARP inhibitor that disrupts cancer cell DNA repair. The clinical trials explore its use both as a standalone treatment and in combination with other therapies.

• Gynecological Cancers: A significant number of trials, totaling 30 studies, are dedicated to gynecological cancers, including 11 trials for Ovarian Cancer, 10 for Fallopian Tube Cancer, 6 for Peritoneal Cancer, 6 for Epithelial Ovarian Cancer, and 3 trials for Endometrial Cancer. Rucaparib is investigated in these conditions because PARP inhibitors have shown promise in treating cancers with specific genetic mutations that affect DNA repair.
• Breast Cancer: Rucaparib is under investigation for Breast Cancer in 5 trials. PARP inhibitors are particularly relevant in breast cancers that have defects in DNA repair genes, such as BRCA mutations, which can make the cancer cells more vulnerable to this type of therapy.
• Prostate Cancer: For Prostate Cancer, Rucaparib is being studied in 4 trials. Similar to breast cancer, prostate cancers with certain genetic alterations in DNA repair pathways may respond well to PARP inhibition.
• General Cancers and Solid Tumors: Rucaparib is also being explored more broadly for various types of cancer. This includes 4 trials for Solid Tumor, 4 trials for unspecified Cancer, and 3 trials for Neoplasms. These studies aim to identify other cancer types or specific patient populations that could benefit from Rucaparib's mechanism of action.

Dosing

Rucaparib is primarily administered orally, as indicated by trial descriptions stating it is "Given PO" and "orally." The drug is typically taken daily, with some regimens specifying twice-daily administration.

Various strengths and combinations of Rucaparib have been investigated in clinical trials:

• Monotherapy: Rucaparib has been studied as a single agent, with a common dose being 600 mg taken orally twice daily, continuously for 28 days or as continuous dosing. Other monotherapy doses include 200 mg, 300 mg, and 400 mg.
• Combination Therapy: Rucaparib is frequently studied in combination with other anticancer agents. Examples include:
  • With enzalutamide or abiraterone.
  • With chemotherapy agents like carboplatin and paclitaxel, sometimes also with bevacizumab.
  • With immunotherapies such as nivolumab, pembrolizumab, or atezolizumab.
  • With other targeted therapies like lucitanib, sacituzumab govitecan, or irinotecan.
  • As part of complex regimens involving agents like PLX038 (PEGylated SN38) at doses of 200 mg, 300 mg, or 400 mg of Rucaparib.

The specific dosage, frequency, and duration of Rucaparib treatment can vary significantly depending on the type of cancer being treated, whether it's used alone or in combination, and the phase of the clinical trial. Patients should always follow the instructions provided by their healthcare provider.

Side Effects

Nausea was the most common side effect reported in clinical trials for Rucaparib. Approximately 66.2% of patients taking Rucaparib experienced nausea, compared to 45.0% of patients on placebo. Other common side effects reported by patients taking Rucaparib, compared to placebo, included:

• Fatigue: 48.1% on Rucaparib vs 36.6% on placebo
• Anemia (low red blood cell count): 44.9% on Rucaparib vs 26.4% on placebo
• Increased alanine aminotransferase (a liver enzyme): 44.3% on Rucaparib vs 24.2% on placebo
• Increased aspartate aminotransferase (a liver enzyme): 39.3% on Rucaparib vs 22.0% on placebo
• Vomiting: 34.1% on Rucaparib vs 18.8% on placebo
• Constipation: 30.6% on Rucaparib vs 18.4% on placebo
• Diarrhea: 29.5% on Rucaparib vs 22.2% on placebo
• Abdominal pain: 27.1% on Rucaparib vs 24.1% on placebo
• Dysgeusia (altered taste): 25.2% on Rucaparib vs 12.8% on placebo

Clinical Trial Results

Triple-Negative Breast Cancer

In a study (NCT01074970) of patients with triple-negative breast cancer and BRCA1/2 mutations, Rucaparib in combination therapy was compared to cisplatin monotherapy. After two years, 64.1% of patients in the Rucaparib combination arm were disease-free, compared to 54.2% in the cisplatin arm. After five years, 50.1% of patients in the Rucaparib combination arm were disease-free, compared to 38.3% in the cisplatin arm.

Ovarian Cancer

In a Phase I/II study (NCT01482715) involving patients with solid tumors or gBRCA mutation ovarian cancer, Rucaparib demonstrated a median duration of response of 318 days in one part of the study (Part 2B) and 270 days in another (Part 2A) for patients receiving 600 mg twice daily. The overall response rate was observed in 25 participants in Part 2A and 7 participants in Part 2B (total number of participants in these arms was not provided for percentage calculation). Median progression-free survival was 280 days in Part 2B and 260 days in Part 2A. Median overall survival for patients in Part 2B was 764 days.

The ARIEL2 study (NCT01891344) investigated Rucaparib in patients with platinum-sensitive, relapsed ovarian, fallopian tube, or primary peritoneal cancer. In Part 1 of the study, the objective response rate (ORR) was highest in patients with tumor BRCA (tBRCA) mutations at 80.0%, followed by 33.3% in non-tBRCA LOH Unknown, 28.0% in non-tBRCA LOH+, and 10.0% in non-tBRCA LOH- subgroups. Median progression-free survival (PFS) in Part 1 was 388 days for tBRCA patients and 174 days for non-tBRCA LOH+ patients. In Part 2 of the study, median overall survival was 22.7 months for tBRCA patients and 14.7 months for non-tBRCA LOH+ patients.

The ARIEL3 study (NCT01968213) evaluated Rucaparib as maintenance therapy in patients with relapsed high-grade serous or endometrioid ovarian cancer. Patients taking Rucaparib 600 mg tablets had a median progression-free survival of 13.7 months as assessed by independent radiology review, compared to 5.4 months for those on placebo. Investigator-assessed progression-free survival was 10.8 months for Rucaparib patients versus 5.4 months for placebo. Median overall survival was 36.0 months for Rucaparib patients, compared to 43.2 months for placebo patients.

Currently Recruiting Trials

Where to Participate

• New York, New York (4 sites)
• Boston, Massachusetts (3 sites)
• Philadelphia, Pennsylvania (2 sites)
• Cincinnati, Ohio (2 sites)
• Nashville, Tennessee (2 sites)
• San Francisco, California (2 sites)
• Madison, Wisconsin (2 sites)
• Orlando, Florida (1 site)
• Tampa, Florida (1 site)
• Chicago, Illinois (1 site)

Development Timeline