Rina-S for Ovarian Cancer

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Genmab

Must be taking: Platinum chemotherapy, Bevacizumab, PARP inhibitors, Mirvetuximab

Must not be taking: Topoisomerase inhibitors

Disqualifiers: Platinum-refractory, CNS metastases, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase 3 study will be conducted in different countries all over the world. The purpose of this study is to compare how well Rina-S works against platinum-resistant ovarian cancer compared to chemotherapy drugs that are already approved and used for platinum-resistant ovarian cancer. Treatment in this study could be Rina-S or it could be 1 of 4 indicated chemotherapy agents that are considered standard medical care. There is an equal (50:50) chance of getting Rina-S or an approved chemotherapy agent as treatment in this study. No one will know what treatment they are assigned to until the first dose. All participants will receive active drug; no one will be given placebo.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What safety data exists for Rina-S (olaparib) in humans?

Olaparib, also known as Rina-S, has been shown to be generally safe in humans, with common side effects including mild anemia (low red blood cell count), fatigue, vomiting, diarrhea, and nausea. In some cases, more severe side effects like neutropenia (low white blood cell count) and thrombocytopenia (low platelet count) have been observed, especially when combined with other treatments.

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Eligibility Criteria

This trial is for those with high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer who've had platinum-based therapy and are platinum-resistant. They must have positive FRα expression and no contraindications to bevacizumab unless documented. Those treated with PARP inhibitors due to BRCA mutations can join if mirvetuximab soravtansine is available locally.

Inclusion Criteria

I have received bevacizumab for my condition if it was recommended and available.

Participants may be enrolled regardless of FRα expression level

I have BRCA mutation and received a PARP inhibitor after responding to platinum-based chemotherapy.

Exclusion Criteria

I have been treated with a specific drug that targets cancer cells.

My cancer did not respond to initial platinum-based chemotherapy.

I have active brain metastases or carcinomatous meningitis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Rina-S or one of four chemotherapy agents as treatment for platinum-resistant ovarian cancer

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Participant Groups

The study compares Rina-S against standard chemotherapy drugs (PLD, Gemcitabine, Paclitaxel, Topotecan) for treating platinum-resistant ovarian cancer. Participants have a 50:50 chance of receiving either Rina-S or one of the chemotherapies without knowing which one until the first dose.

Group I: Rina-S Experimental Treatment 1 Intervention

Group II: Investigator's Choice Active Control 4 Interventions

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Trials365, LLC Shreveport, LA

Center of Hope Reno, NV

St. Elizabeth Healthcare - Edgewood Edgewood, KY

FirstHealth Outpatient Cancer Center Pinehurst, NC

Who Is Running the Clinical Trial?

Genmab Lead Sponsor

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib maintenance therapy in platinum-sensitive ovarian cancer patients with BRCA mutations: a meta-analysis on randomized controlled trials. [2020] Background: Olaparib, a potent oral poly (ADP-ribose) polymerase inhibitor, exhibits antitumor activity and prevents the recurrence in advanced ovarian cancer. In this article, we assessed the efficacy and safety of olaparib maintenance therapy on platinum-sensitive ovarian cancer patients with BRCA mutations through a meta-analysis of available randomized controlled trials (RCTs) to provide more evidence for its clinical applications. Methods: We searched PubMed, Embase, Wanfang, CNKI, Web of Science, Cochrane Library, and VIP databases from 1 August 2018 to identify RCTs and finally included four RCTs (seven articles) with 567 eligible participants beyond the participants, interventions, comparisons, outcomes, and study design regulation. The outcomes of olaparib efficacy including progression-free survival (PFS) and overall survival (OS) were measured by HR and 95% CI, while the quality of life was evaluated by calculating the combination of P-value. Seven common adverse events were tested by risk ratio and 95% CI as the outcomes of olaparib safety. These data were analyzed, and the forest figures were produced using Review Manager 5.3. Results: Compared with other interventions (ie, placebo or chemotherapy drugs), olaparib significantly prolonged PFS (HR=0.31, 95% CI=0.15-0.62) and slightly improved OS (HR=0.75, 95% CI=0.56-0.99), but did not influence the quality of life (P=0.058) in the patients with platinum-sensitive BRCA-mutated ovarian cancer. Additionally, the toxicity profile of olaparib involved anemia, fatigue, vomiting, diarrhea, and nausea with grade 1-2. Conclusion: This meta-analysis suggests that olaparib maintenance therapy is effective and well-tolerated for the patients with platinum-sensitive BRCA-mutated ovarian cancer. More updated RCTs and long-term follow-up should be conducted to compare and analyze the efficacy and toxicity of olaparib at different doses in ovarian cancer patients.

2. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life in women with recurrent ovarian cancer receiving paclitaxel plus trebananib or placebo (TRINOVA-1). [2020] To evaluate the influence of treatment on health-related quality of life (HRQoL) in 919 women with recurrent ovarian cancer enrolled in the TRINOVA-1 study, a randomized, placebo-controlled phase III study that demonstrated that trebananib 15 mg/kg QW plus weekly paclitaxel significantly improved progression-free survival (PFS) compared with placebo plus weekly paclitaxel (7.2 versus 5.4 months; hazard ratio, 0.66; 95% confidence interval 0.57-0.77; P

3. Australia pubmed.ncbi.nlm.nih.gov

Olaparib dose re-escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series. [2021] Few real-world studies have reported detailed management and dose adjustment strategies of adverse events (AEs) of ovarian cancer (OC) patients treated with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib. This case series aimed to describe olaparib AEs in Chinese OC patients in real-life settings and to explore dose modification strategies.

4. Belgium pubmed.ncbi.nlm.nih.gov

New perspective on maintenance therapies for platinum- sensitive recurrent ovarian cancer in women with germline and somatic mutations in BRCA1 and BRCA2 genes. [2023] Ovarian cancer (OC) is the seventh most common cancer in women. Although women diagnosed with OC are usually treated frontline with platinum-based chemotherapy, most of them relapse once treatment is halted. Therefore, maintenance therapies have been developed to secure the response and delay further chemotherapy. There are two established maintenance therapies for women affected by platinum-sensitive recurrent OC: bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, and olaparib, an inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARPi). Loss-of-function mutations in genes in the homologous recombination pathway, especially BRCA1 and BRCA2, predict higher rates of platinum sensitivity, better overall survival (OS), and better response to PARPi in women with OC. Among patients with platinum-sensitive recurrent OC, a BRCA mutation is the first genetically defined predictive marker for targeted therapy, since these patients are most likely to benefit from treatment with a PARPi, such as olaparib. In patients with platinum-sensitive recurrent OC without a BRCA mutation, bevacizumab currently seems to be the best maintenance option. Women with OC are progressively more routinely screened for germline BRCA mutations, and the implication of somatic BRCA mutations is increasingly being recognized in OC. Therefore, the recommendations should be updated to reflect the importance of both types of mutations. Together, these data highlight the fact that treatment of recurrent OC can be optimized using genomic contributions to individualize therapy and to improve treatment response.

5. United States pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in heavily pretreated recurrent high-grade serous ovarian cancer at low genetic risk. [2023] Purpose: To investigate maximum tolerated dose (MTD), activity and predictive biomarkers of olaparib with carboplatin in BRCA wild-type (BRCAwt) high grade serous ovarian carcinoma (HGSOC) patients. Methods: A 3+3 dose escalation study examined olaparib capsules (400 mg twice daily [BID], days 1-7) with carboplatin (AUC3-5 on day 1) every 21 days for 8 cycles, followed by olaparib 400 mg BID maintenance. Blood and tumor biopsy samples were collected pre- and on-treatment in the expansion cohort for PAR levels and proteomic endpoints. Results: 30 patients (median 7 prior regimens [2-12], 63% (19/30) platinum-resistant) were enrolled. Dose-limiting toxicity was thrombocytopenia/neutropenia, and infection with carboplatin AUC5 (2/6 patients). MTD was olaparib 400 mg BID + carboplatin AUC4. Grade 3/4 adverse events (>10%) included neutropenia (23%), thrombocytopenia (20%), and anemia (13%). Five of 25 (20%) evaluable patients had partial response (PR; median 4.5 months [3.3-9.5]). Clinical benefit rate (PR + stable disease ≥4 months) was 64% (16/25). A greater decrease in tissue PAR levels was seen in the clinical benefit group versus no benefit (median normalized linear change -1.84 [-3.39- -0.28] vs 0.51 [-0.27- 1.29], p = 0.001) and a DNA repair score by proteomics did not correlate with response. Conclusions: The olaparib and carboplatin combination is tolerable and has clinical benefit in subsets of heavily pretreated BRCAwt HGSOC, independent of platinum sensitivity.