VS-6063 + Chemotherapy for Ovarian Cancer

Overseen By Alexandrea Cronin, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Michael McHale

Must not be taking: Kinase inhibitors

Disqualifiers: Platinum-refractory cancer, Recent malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 years

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for ovarian cancer that combines an experimental drug, VS-6063, with two approved chemotherapy drugs, carboplatin and paclitaxel. The goal is to see if this combination is safe and can reduce cancer cells. Patients will take VS-6063 by mouth and receive the other two drugs through infusions.

Will I have to stop taking my current medications?

The trial requires that any hormonal therapy directed at the tumor be stopped at least one week before joining, and any other cancer treatments, including biologic and immunologic agents, must be stopped at least three weeks before joining. The protocol does not specify about other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination VS-6063, Carboplatin, and Paclitaxel for ovarian cancer?

Research shows that combining paclitaxel with carboplatin is effective for treating ovarian cancer, especially in patients who are sensitive to platinum-based treatments. Paclitaxel has been found to be highly active in patients with platinum-resistant ovarian cancer, and dose-dense regimens of paclitaxel and carboplatin have improved survival rates. ^{1 2 3 4 5}

What safety data exists for the combination of VS-6063, carboplatin, and paclitaxel in treating ovarian cancer?

Carboplatin and paclitaxel have been studied together in ovarian cancer, showing that they can be safely administered, though they may cause side effects like neurotoxicity (nerve damage), alopecia (hair loss), and hypersensitivity (allergic reactions). The combination of docetaxel and carboplatin has been found to have a tolerable safety profile, with more myelosuppression (bone marrow suppression) but less neuropathy (nerve damage) compared to paclitaxel and carboplatin. There is no specific safety data available for VS-6063 in this context. ^{6 7 8 9 10}

What makes the drug VS-6063 + Chemotherapy unique for ovarian cancer?

The drug VS-6063 combined with chemotherapy is unique because it includes Defactinib, a novel agent that targets cancer stem cells, potentially enhancing the effectiveness of standard chemotherapy drugs like carboplatin and paclitaxel, which are commonly used in ovarian cancer treatment. ^{1 11 12 13 14}

Research Team

Michael McHale

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for women with certain types of ovarian cancer that came back or didn't go away after platinum-based chemo. They must have completed this treatment within the last 6 months and can't have had more than two chemo treatments for the recurrence. Participants need to be free from infections, recovered from past treatments, not pregnant, and using birth control.

Inclusion Criteria

I have had 2 or fewer chemotherapy treatments for my recurring cancer.

I am a woman who can have children, have a negative pregnancy test, and use birth control.

My cancer is one of the specified types, like serous or clear cell adenocarcinoma.

Exclusion Criteria

My ovarian, fallopian tube, or peritoneal cancer is not responding to platinum-based chemotherapy.

I am not on current cancer treatments and stopped any cancer-directed treatments at least 3 weeks ago.

Patients who are pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive VS-6063 by mouth, as well as carboplatin and paclitaxel infusions

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Carboplatin
• Paclitaxel
• VS-6063

Trial Overview The ROCKIF Trial is testing a combination of VS-6063 (an experimental drug), carboplatin, and paclitaxel in treating ovarian cancer. Patients will take VS-6063 orally and receive infusions of carboplatin and paclitaxel to see if this regimen safely reduces cancer cells.

Participant Groups

Group I: Defactinib (VS-6063) +Carboplatin/Paclitaxel Experimental Treatment 3 Interventions

Defactinib (VS-6063) +Carboplatin/Paclitaxel

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Michael McHale

Lead Sponsor

Trials

1

Recruited

90+

Nine Girls Ask

Collaborator

Trials

1

Recruited

90+

Verastem, Inc.

Industry Sponsor

Trials

42

Recruited

2,800+

Findings from Research

Cytoreductive surgery followed by platinum-based chemotherapy, particularly with carboplatin, remains the standard treatment for advanced epithelial ovarian cancer, but most patients are not cured, highlighting the need for improved therapies.

Paclitaxel, a novel agent effective in platinum-resistant ovarian cancer, is being tested in combination with platinum compounds in clinical trials for previously untreated patients, aiming to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ovarian cancer: current status. Ozols, RF.[2015]

In a phase 2 study involving 76 patients with suboptimal residual ovarian cancer, the combination of intraperitoneal carboplatin and dose-dense paclitaxel resulted in a high objective clinical response rate of 83.1%.

The treatment demonstrated promising median progression-free survival of 18.3 months and overall survival of 55.5 months, indicating its efficacy as a front-line chemotherapy option, although it was associated with significant side effects like neutropenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of intraperitoneal carboplatin plus intravenous dose-dense paclitaxel in front-line treatment of suboptimal residual ovarian cancer. Hasegawa, K., Shimada, M., Takeuchi, S., et al.[2021]

In a study of 189 patients with recurrent platinum-sensitive ovarian cancer, the combination of carboplatin and pegylated liposomal doxorubicin (CLD) showed similar overall response rates to carboplatin and paclitaxel (CP), but with significantly lower rates of neurotoxicity and alopecia, making it a safer option.

Discontinuation due to toxicity was notably higher in the CP group (13.5%) compared to the CLD group (3%), suggesting that CLD may offer a better safety profile for patients undergoing second-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study of carboplatin plus pegylated liposomal doxorubicin versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer patients: a Hellenic Cooperative Oncology Group study. Bafaloukos, D., Linardou, H., Aravantinos, G., et al.[2021]

In a phase II study involving 43 patients with relapsed platinum-sensitive epithelial ovarian cancer, the combination of carboplatin and gemcitabine resulted in a 40.5% objective response rate, with 10 complete and 5 partial responses, indicating significant efficacy.

The treatment was well tolerated, with a median overall survival of 24.5 months and a median time to progression of 9 months, although some patients experienced Grade 3 or 4 toxicities such as neutropenia, anemia, and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line chemotherapy with gemcitabine and carboplatin in paclitaxel-pretreated, platinum-sensitive ovarian cancer patients. A Hellenic Cooperative Oncology Group Study. Papadimitriou, CA., Fountzilas, G., Aravantinos, G., et al.[2022]

In a study involving 637 patients with advanced ovarian cancer, the dose-dense regimen of paclitaxel and carboplatin significantly improved median progression-free survival to 28.2 months compared to 17.5 months with the conventional regimen.

The dose-dense treatment also resulted in a longer median overall survival of 100.5 months versus 62.2 months for the conventional treatment, suggesting it could become a new standard of care for first-line chemotherapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Katsumata, N., Yasuda, M., Isonishi, S., et al.[2022]

In a phase I-II study involving 50 women with advanced ovarian cancer, the maximum tolerated dose of paclitaxel was determined to be 250 mg/m2, but a safer clinical maximum was suggested to be 225 mg/m2 due to observed neurotoxicity.

The combination of carboplatin and paclitaxel resulted in a high overall response rate of 78%, with a complete response rate of 62%, indicating that this treatment regimen is effective for patients with advanced ovarian carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I-II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. Bolis, G., Scarfone, G., Zanaboni, F., et al.[2019]

A frail 79-year-old woman with advanced peritoneal carcinoma experienced disease stabilization and improved quality of life after receiving weekly single-agent carboplatin (AUC = 2) with negligible toxicity.

Weekly carboplatin treatment is a promising alternative for frail and elderly patients, potentially reducing side effects while maintaining effectiveness compared to standard combination chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly carboplatin in a frail elderly woman with advanced peritoneal carcinoma. Piura, B., Meirovitz, M.[2013]

Docetaxel combined with carboplatin is a feasible and tolerable first-line treatment option for newly diagnosed epithelial ovarian cancer, showing no significant difference in progression-free or overall survival compared to the traditional paclitaxel and carboplatin combination in a study of 1,077 patients.

While docetaxel was associated with more myelosuppression, it resulted in fewer cases of neuropathy compared to paclitaxel, leading to better quality-of-life outcomes for patients receiving docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. Vasey, PA.[2018]

In a study of 62 patients with ovarian, fallopian tube, or primary peritoneal cancer, BRCA mutations did not significantly increase the likelihood of hypersensitivity reactions (HSRs) to carboplatin, with 30.8% of BRCA-mutated patients experiencing reactions compared to 44.9% of BRCA wild-type patients.

However, BRCA mutations were significantly associated with a lower incidence of HSRs to paclitaxel, where only 7.7% of BRCA-mutated patients had reactions compared to 53.1% of BRCA wild-type patients, indicating a potential protective effect of BRCA mutations against paclitaxel-related hypersensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Hypersensitivity Reactions to Carboplatin or Paclitaxel in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer With or Without BRCA1 or BRCA2 Mutations. Garcia, A., Frahm, C., Jeter, JM., et al.[2023]

In a study of 40 patients with ovarian, fallopian tube, or peritoneal cancers, the docetaxel/carboplatin regimen resulted in significantly higher rates of hematologic toxicity, with 80% of patients experiencing some form of it, including severe neutropenia in 45%.

Conversely, the paclitaxel/carboplatin group had a lower incidence of neutropenia and a higher occurrence of neuropathy, but both treatment regimens showed equivalent therapeutic efficacy, indicating that while side effects differ, the effectiveness in treating cancer remains similar.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel versus paclitaxel for adjuvant treatment of ovarian cancer: case-control analysis of toxicity. Hsu, Y., Sood, AK., Sorosky, JI.[2019]

Patients with recurrent ovarian cancer are categorized as either platinum-sensitive or platinum-resistant, which influences treatment options; platinum-sensitive patients often benefit from re-treatment with paclitaxel/platinum combinations, while platinum-resistant patients may receive single-agent therapies like altretamine or topotecan.

For platinum-sensitive patients with minimal residual disease, intensive intraperitoneal therapy with cisplatin and paclitaxel shows the most promise for long-term disease-free survival, highlighting the importance of tailored treatment strategies based on disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory and recurrent ovarian cancer. Alberts, DS.[2005]

The combination of platinum and paclitaxel has been established as the standard treatment for advanced ovarian cancer since the late 1990s, with further studies suggesting that adding noncross-resistant drugs like epirubicin may enhance treatment efficacy.

In a phase III trial involving 1281 patients, 87% completed six cycles of treatment, providing valuable data on treatment response and toxicity, which will help assess the effectiveness of the new combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The integration of anthracyclines in the treatment of advanced ovarian cancer. Lück, HJ., Du Bois, A., Weber, B., et al.[2018]

Paclitaxel has been established as an effective treatment for newly diagnosed ovarian cancer patients, leading to its incorporation into primary chemotherapy regimens, particularly in combination with cisplatin as the new standard in the U.S.

Ongoing clinical trials are exploring various strategies to optimize paclitaxel-based chemotherapy, including comparisons of different platinum-based drugs and infusion schedules, as well as evaluating high-dose therapies with stem cell support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of advanced ovarian cancer: current status and future directions. Ozols, RF., Vermorken, JB.[2015]

Combination chemotherapy is more effective than single-agent therapy for recurrent ovarian cancer, indicating a need for multi-drug approaches in treatment.

While intraperitoneal drug administration has shown improved survival in patients with small-volume stage III disease, it comes with significant toxicity, highlighting the need to balance efficacy and safety in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges for chemotherapy in ovarian cancer. Ozols, RF.[2020]

References

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

Treatment of ovarian cancer: current status. [2015]

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

A phase 2 study of intraperitoneal carboplatin plus intravenous dose-dense paclitaxel in front-line treatment of suboptimal residual ovarian cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A randomized phase II study of carboplatin plus pegylated liposomal doxorubicin versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer patients: a Hellenic Cooperative Oncology Group study. [2021]

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

Second-line chemotherapy with gemcitabine and carboplatin in paclitaxel-pretreated, platinum-sensitive ovarian cancer patients. A Hellenic Cooperative Oncology Group Study. [2022]

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

Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A phase I-II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

Weekly carboplatin in a frail elderly woman with advanced peritoneal carcinoma. [2013]

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

Role of docetaxel in the treatment of newly diagnosed advanced ovarian cancer. [2018]

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

Incidence of Hypersensitivity Reactions to Carboplatin or Paclitaxel in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer With or Without BRCA1 or BRCA2 Mutations. [2023]

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

Docetaxel versus paclitaxel for adjuvant treatment of ovarian cancer: case-control analysis of toxicity. [2019]

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

Treatment of refractory and recurrent ovarian cancer. [2005]

12. England pubmed.ncbi.nlm.nih.gov

The integration of anthracyclines in the treatment of advanced ovarian cancer. [2018]

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

Chemotherapy of advanced ovarian cancer: current status and future directions. [2015]

14. England pubmed.ncbi.nlm.nih.gov

Challenges for chemotherapy in ovarian cancer. [2020]