Clinical Trial Match-List Intervention for Cancer Research Access

(DISRUPT Trial)

Recruiting at 3 trial locations

Overseen By Radhi Yagnik

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Unable to consent, language barrier, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

644 Participants Needed

Trial Summary

What is the purpose of this trial?

This proposal brings together multidisciplinary teams from four New York City institutions charged with reducing cancer disparities that affect approximately two million people residing in some of the most diverse and underserved communities in the United States. The intent of this collaborative research is captured by its acronym, DISRUPT: Diversity \& IncluSion in Research Underpinning Prevention \& Therapy Trials. To disrupt the norms that maintain heightened risk and poorer outcomes experienced by BIPOC, the research team propose three integrated and synergistic aims to improve diversity and inclusion in CTs through disruptive approaches at the community (Aim 1), provider, system and patient (Aim 2), and basic and translational scientist levels (Aim 3). All three aims focus on metrics for changing norms reified in institutional policies and established practice that will provide essential evidence to translate and scale these changes to institutions and networks involved in cancer treatment research. In Aim 1, the research team will partner with local organizations to formulate and disseminate new norms regarding cancer care and research and diffuse these new norms throughout the community via community organizations and Health Ambassadors bringing a different vantage point on CTs, raising awareness and increasing demand for access to cancer research. In Aim 2, the research team will create an electronic approach to identify key clinical characteristics of patients and trials and match patients and trials and bring these data to patients and their physicians at the time of key decisions. In Aim 3, the research team will provide and integrate essential experiential training in diversity, social determinants of health and the importance of conducting community-relevant work into basic and translational science training. This DISRUPT proposal provides the foundation to disrupt norms about cancer clinical trials in our communities, delivery systems and scientific research enterprises.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Olaparib?

Research shows that Olaparib significantly extends the time patients with certain types of breast and prostate cancer live without their disease getting worse compared to standard treatments. It also improves the quality of life for these patients. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Olaparib, also known as Lynparza, has been studied for safety in various cancers, including ovarian and breast cancer. It is generally considered safe, but like all medications, it can have side effects, so it's important to discuss these with your doctor. ^{2 4 6 7 8}

How does the drug olaparib differ from other treatments for breast cancer?

Olaparib is unique because it is a PARP inhibitor (a type of drug that blocks a protein used by cells to repair damage to their DNA) and is specifically used for patients with HER2-negative breast cancer who have a BRCA mutation. Unlike traditional chemotherapy, olaparib is taken orally and has shown to significantly prolong progression-free survival in these patients. ^{1 5 8 9 10}

Research Team

Nina Bickell

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults over 21 with invasive breast, prostate, or liver cancer who are facing a treatment decision. Participants must be able to consent and communicate in English or Spanish. Oncologists and related specialists caring for these patients can also join if they agree.

Inclusion Criteria

For provider recruitment, oncologists, and advanced practitioners caring for patients with breast, prostate, liver cancer including medical, surgical, radiation oncologists, interventional radiologists, urologists & hepatologists.

Patients of doctors who have consented to participate

I am over 21 and have breast, prostate, or liver cancer needing treatment decisions.

Exclusion Criteria

You are not in urgent need of medical treatment.

I do not have invasive breast, prostate, or liver cancer.

I cannot understand English or Spanish.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention Implementation

Implementation of interventions aimed at improving diversity and inclusion in clinical trials through community engagement, electronic matching of patients to trials, and training in diversity and social determinants of health.

6 months

Follow-up

Participants are monitored for changes in clinical trial accrual rates and feedback from physicians and patients post-intervention.

6 months

Treatment Details

Interventions

• Clinical trial match-list
• Match-list intervention

Trial Overview DISRUPT aims to improve diversity in clinical trials (CTs) by creating new community norms around cancer care, matching patients with CTs electronically at decision points, and integrating training on diversity into scientific research.

Participant Groups

Group I: Patient Participants Active Control 1 Intervention

Patients with invasive breast, prostate or liver cancer, who face a treatment decision

Group II: Physician Participants Active Control 1 Intervention

Oncologists, and advanced practitioners caring for patients with breast, prostate, liver cancer including medical, surgical, radiation oncologists, interventional radiologists, urologists \& hepatologists

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

In the phase III OlympiAD trial, olaparib significantly improved progression-free survival (PFS) in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer, with a median PFS of 8.0 months compared to 3.8 months for chemotherapy, indicating a strong efficacy of olaparib.

Subgroup analyses showed consistent benefits of olaparib across various patient characteristics, including hormone receptor status and prior chemotherapy, with higher objective response rates and improved quality of life compared to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial. Senkus, E., Delaloge, S., Domchek, SM., et al.[2023]

Olaparib significantly improves overall survival in patients with recurrent platinum-sensitive ovarian cancer, with a hazard ratio of 1.24 based on a meta-analysis of 7 randomized controlled trials involving 2406 patients.

However, the treatment is associated with a higher incidence of adverse events, particularly for grades 3 or higher, indicating that while olaparib is effective, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. Chen, Q., Li, X., Zhang, Z., et al.[2022]

The PROfound trial shows that testing for genetic alterations in homologous recombination, particularly BRCA1, BRCA2, and ATM, is beneficial for all patients with metastatic, castration-resistant prostate cancer (mCRPC).

Olaparib significantly improves progression-free survival, objective response rate, and time to pain progression in patients with these genetic alterations, marking it as the first effective treatment in a genomically-selected group for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting defects in homologous recombination repair for metastatic, castration-resistant prostate cancer. Chau, V., Madan, RA., Figg, WD.[2021]

The combination of olaparib and durvalumab (O+D) showed a progression-free survival rate of 35% at 6 months in patients with advanced solid tumors, including rare cancers with homologous recombination repair (HRR) defects, indicating its efficacy in this challenging patient population.

O+D was found to be safe, with only 6% of patients experiencing serious adverse events, and it produced durable objective tumor responses in several rare cancer types, suggesting it could be a promising treatment option without new toxicity concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations. Thavaneswaran, S., Kansara, M., Lin, F., et al.[2023]

Olaparib, an oral PARP-inhibitor, significantly improves progression-free survival in HER2-negative advanced breast cancer patients with BRCA1/2 mutations compared to standard chemotherapy, based on a randomized Phase III trial.

The trial also indicated an overall survival benefit for patients who had not received prior chemotherapy for metastatic disease, highlighting olaparib's potential as an effective treatment option in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. Griguolo, G., Dieci, MV., Miglietta, F., et al.[2021]

In the BAROCCO trial involving 123 patients with recurrent platinum-sensitive ovarian cancer, the combination of cediranib and olaparib did not show superior progression-free survival (PFS) compared to paclitaxel chemotherapy, with median PFS of 5.6 months for the continuous cediranib-olaparib group and 3.1 months for the control group.

Despite not outperforming chemotherapy, the cediranib-olaparib combination was associated with a lower rate of treatment discontinuation due to adverse events (5% in the intermittent arm) and offers a potential non-chemotherapy treatment option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer. Colombo, N., Tomao, F., Benedetti Panici, P., et al.[2022]

In a study involving 34 patients with BRCA1 or BRCA2 mutated metastatic breast cancer, the combination of olaparib and durvalumab demonstrated promising antitumor activity, with 80% of patients showing disease control at 12 weeks.

The treatment was generally safe, with 32% of patients experiencing grade 3 or worse adverse events, but no treatment-related deaths were reported, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. Domchek, SM., Postel-Vinay, S., Im, SA., et al.[2021]

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

Olaparib, a PARP inhibitor, showed a 36% objective response rate in women with relapsed ovarian cancer and a germline BRCA1/2 mutation, even after they had undergone multiple lines of chemotherapy, indicating its efficacy in this challenging patient population.

The median duration of response to olaparib was 7.4 months, and the safety profile was consistent across patients who had received three or more lines of prior chemotherapy, with similar rates of serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Matulonis, UA., Penson, RT., Domchek, SM., et al.[2022]

Olaparib is particularly effective for patients with BRCA-mutated ovarian cancer, but it also benefits a subset of patients with BRCA wild-type tumors that have loss-of-function mutations in DNA repair genes, showing similar treatment outcomes.

The study suggests that patients with specific HRR gene mutations, even without BRCA mutations, can be identified as a group that may respond well to olaparib, indicating a potential for broader use of this treatment in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. Hodgson, DR., Dougherty, BA., Lai, Z., et al.[2020]

References

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

Olaparib efficacy in patients with germline BRCA-mutated, HER2-negative metastatic breast cancer: Subgroup analyses from the phase III OlympiAD trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review of Olaparib in the Treatment of Recurrent Platinum Sensitive Ovarian Cancer. [2022]

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

Exploiting defects in homologous recombination repair for metastatic, castration-resistant prostate cancer. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A signal-seeking Phase 2 study of olaparib and durvalumab in advanced solid cancers with homologous recombination repair gene alterations. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Olaparib for advanced breast cancer. [2021]

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

Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Olaparib and durvalumab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): an open-label, multicentre, phase 1/2, basket study. [2021]

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

New Adjuvant Treatment for High-Risk Early Breast Cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes. [2020]