Efficacy and Safety Study of AVB-S6-500 in Patients With Platinum-Resistant Recurrent Ovarian Cancer

Recruiting at 15 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Aravive, Inc.

Must not be taking: Anti-cancer therapy

Disqualifiers: Cardiac disease, CNS metastasis, others

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

Compensation: Varies

Number of Visits: Unknown

53 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must wait at least 28 days after your last anti-cancer or hormonal therapy before starting the study drug.

What data supports the effectiveness of the drug AVB-S6-500, Paclitaxel, Taxol, Onxol, Abraxane, Paclitaxel, Pegylated liposomal doxorubicin (PLD), Placebo, Control, Dummy Treatment?

Research shows that Abraxane, a form of paclitaxel, is effective in treating metastatic breast cancer with less toxicity compared to traditional paclitaxel. Additionally, combining pegylated liposomal doxorubicin (PLD) with paclitaxel has shown a high response rate and manageable side effects in patients with metastatic breast cancer. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The treatment, which includes pegylated liposomal doxorubicin (PLD) and paclitaxel, has been studied in patients with breast cancer and is generally considered safe with manageable side effects. Common side effects include hand-foot syndrome (skin reaction on palms and soles), mouth sores, and low white blood cell counts, but no serious heart-related issues were observed. ^{2 6 7 8 9}

What makes the drug AVB-S6-500 combined with Paclitaxel and Pegylated liposomal doxorubicin unique?

This drug combination is unique because it uses pegylated liposomal doxorubicin, which delivers the active ingredient directly to the tumor, reducing side effects compared to traditional doxorubicin. Additionally, the combination with paclitaxel has shown effectiveness in treating metastatic breast cancer with manageable side effects, especially in patients at high risk of heart-related issues. ^{2 3 7 10 11}

What is the purpose of this trial?

This trial tests a new drug, AVB-S6-500, combined with existing cancer treatment in patients with ovarian cancer that hasn't improved with other treatments. The goal is to see if this new combination works better than the existing treatments alone.

Research Team

Amy Franke

Principal Investigator

Aravive, Inc.

Eligibility Criteria

Inclusion Criteria

Histologically confirmed and documented recurrent ovarian, fallopian tube, and peritoneal cancer.

Received at least 1 but not more than 3 therapy regimens, not including maintenance or adjuvant therapy

Must have ovarian cancer that is measurable according to RECIST 1.1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Open-label treatment with AVB-S6-500 in combination with PLD or Pac to evaluate safety and tolerability

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• AVB-S6-500
• Paclitaxel
• Pegylated liposomal doxorubicin (PLD)
• Placebo

Participant Groups

Group I: Phase 2: AVB-S6-500+Pac Experimental Treatment 2 Interventions

Group II: Phase 2: AVB-S6-500+PLD Experimental Treatment 2 Interventions

Group III: Phase 1b: AVB-S6-500+Pac Experimental Treatment 2 Interventions

Group IV: Phase 1b: AVB-S6-500+PLD Experimental Treatment 2 Interventions

Group V: Phase 2: Placebo+Pac Active Control 2 Interventions

Group VI: Phase 2: Placebo+PLD Active Control 2 Interventions

Who Is Running the Clinical Trial?

Aravive, Inc.

Lead Sponsor

Trials

9

Recruited

590+

Findings from Research

Nab-paclitaxel (Abraxane(®)) has been approved by the FDA for treating breast cancer after chemotherapy failure, showing superior efficacy compared to traditional paclitaxel (Taxol(®)).

This new formulation not only demonstrates better effectiveness but also has less toxicity, which enhances its safety profile and therapeutic index, making it a promising option for combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. Montero, AJ., Adams, B., Diaz-Montero, CM., et al.[2021]

In a pilot study involving 17 patients with advanced hepatocellular carcinoma, pegylated liposomal doxorubicin (PLD) demonstrated a clinical benefit response in 50% of participants, including a 7% rate of complete remission.

The treatment was associated with moderate toxicities, suggesting it is relatively safe, and the positive results indicate that further research on PLD for this condition is justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma. Schmidinger, M., Wenzel, C., Locker, GJ., et al.[2018]

The maximum tolerated doses (MTD) for pegylated liposomal doxorubicin (PLD) and paclitaxel (PTX) in patients with metastatic breast cancer were determined to be 35 mg/m2 and 160 mg/m2, respectively, indicating a safe dosing strategy for further studies.

In this phase-I study involving 23 patients, the combination of PLD and PTX showed promising efficacy, with 52.6% of evaluable patients achieving an objective response, suggesting that this regimen is active and has manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline. Hong, RL., Lin, CH., Chao, TY., et al.[2018]

In a study of 42 patients receiving cumulative doses of pegylated liposomal doxorubicin (doxil) exceeding 500 mg/m2, none developed clinical congestive heart failure, indicating a favorable safety profile for higher doses compared to traditional doxorubicin.

While five patients experienced a drop in left ventricular ejection fraction (LVEF), the overall risk of cardiomyopathy appears significantly lower with doxil, even in patients previously treated with doxorubicin, suggesting that doxil may be a safer option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Safra, T., Muggia, F., Jeffers, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel in the treatment of metastatic breast cancer: a comprehensive review. [2021]

2. Greece pubmed.ncbi.nlm.nih.gov

Weekly pegylated liposomal doxorubicin and paclitaxel in patients with metastatic breast carcinoma: A phase II study. [2021]

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

Efficacy, biodistribution, and pharmacokinetics of CD22-targeted pegylated liposomal doxorubicin in a B-cell non-Hodgkin's lymphoma xenograft mouse model. [2022]

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

Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma. [2018]

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

Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. [2022]

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

Neoadjuvant chemotherapy with low dose of pegylated liposomal doxorubicin plus weekly paclitaxel in operable and locally advanced breast cancer. [2022]

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

A phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. [2022]

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

Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer. [2018]

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

Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcoma: evidence of symptom palliation from chemotherapy. [2022]

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

Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma. [2022]