AVB-S6-500 for Ovarian Cancer

No longer recruiting at 16 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AVB-S6-500 for individuals with ovarian cancer that recurs and resists platinum-based chemotherapy. It combines AVB-S6-500 with either paclitaxel or pegylated liposomal doxorubicin, two types of chemotherapy. The trial aims to evaluate the effectiveness and safety of this combination compared to a placebo. It seeks participants with ovarian cancer that has returned and resisted treatment after platinum-based drugs, provided they have not undergone more than three different treatments in the past. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies found that the combination of AVB-S6-500 with either pegylated liposomal doxorubicin (PLD) or paclitaxel (Pac) was well-tolerated by patients. Research has shown no major safety concerns. The Drug Monitoring Committee (DMC) identified no safety issues with AVB-S6-500, suggesting the treatment is generally safe.

Paclitaxel, used in this combination, is already a common cancer treatment. It has known side effects, but doctors usually manage them effectively. Similarly, PLD is a standard treatment for some cancers and is generally safe, with manageable side effects.

Overall, earlier studies have shown that the combination of AVB-S6-500 with either PLD or Pac is promising in terms of safety. Although this trial is still in its early stages, the initial findings are encouraging for those considering participation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AVB-S6-500 for treating platinum-resistant recurrent ovarian cancer because it offers a novel approach compared to existing treatments like chemotherapy with paclitaxel or pegylated liposomal doxorubicin (PLD). Unlike traditional options that primarily target cancer cells directly, AVB-S6-500 works by inhibiting the GAS6/AXL signaling pathway, which plays a crucial role in tumor growth and metastasis. This unique mechanism of action could potentially overcome resistance to platinum-based therapies, offering new hope for patients with limited options. Additionally, combining AVB-S6-500 with standard drugs like paclitaxel or PLD may enhance treatment efficacy and improve patient outcomes.

What evidence suggests that this trial's treatments could be effective for platinum resistant recurrent ovarian cancer?

This trial will evaluate the effectiveness of AVB-S6-500 combined with existing cancer treatments like paclitaxel and pegylated liposomal doxorubicin (PLD). Participants will be assigned to different treatment arms: AVB-S6-500 with paclitaxel, AVB-S6-500 with PLD, or a placebo with either paclitaxel or PLD. Research has suggested that AVB-S6-500 is generally well-tolerated and enhances the effectiveness of these treatments in patients with ovarian cancer unresponsive to standard platinum-based therapies. AVB-S6-500 targets a protein called AXL, which aids cancer cell growth. This drug blocks AXL more effectively than other treatments, potentially preventing cancer from spreading. Early evidence indicates that this combination shows promise in managing difficult-to-treat ovarian cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Amy Franke

Principal Investigator

Aravive, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

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

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03639246

Efficacy and Safety Study of AVB-S6-500 in Patients With ... This is a Phase 1b/2 study of AVB-S6-500 in combination with pegylated liposomal doxorubicin (PLD) or paclitaxel (Pac) in patients with platinum resistant ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04729608

Study Details | NCT04729608 | Batiraxcept (AVB-S6-500)/ ... This is a randomized, double-blind Phase 3 study to compare the efficacy and safety of batiraxcept (AVB-S6-500) in combination with paclitaxel (PAC) versus ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34474927/

Phase 1b study of AVB-500 in combination with paclitaxel ... Conclusion: AVB-500 was well-tolerated in combination with PAC or PLD and contributed to the clinical activity of PAC in PROC patients. Subgroup ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20524072

A Study to Evaluate AVB-S6-500 with Paclitaxel vs ... The purpose of this study is to evaluate AVB-S6-500 in combination with paclitaxel (Pac) in patients with platinum resistant recurrent ovarian ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT340711

A phase 3, randomized, double-blind, adaptive, placebo ... AVB-S6-500 is a highly sensitive and specific inhibitor of AXL, with ̃200-fold higher affinity than wild-type (WT) AXL. AVB-S6-500 binds GAS6, the sole ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03639246

Efficacy and Safety Study of AVB-S6-500 in Patients With ... This is a Phase 1b/2 study of AVB-S6-500 in combination with pegylated liposomal doxorubicin (PLD) or paclitaxel (Pac) in patients with platinum resistant ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT03639246

Efficacy and Safety Study of AVB-S6-500 in Patients With ... The DMC did not identify any safety concerns with AVB-500....The company anticipates reporting safety and pharmacokinetic data from this Phase 1b trial in mid- ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0090825821013184

Phase 1b study of AVB-500 in combination with paclitaxel ... AVB-500 was well-tolerated in combination with PAC or PLD and contributed to the clinical activity of PAC in PROC patients.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10321312/

Pegylated liposomal doxorubicin for relapsed epithelial ... To evaluate the efficacy and safety of PLD, with or without other anti‐cancer drugs, in women with relapsed high grade epithelial ovarian cancer (EOC). Search ...

10. adisinsight.springer.com adisinsight.springer.com/trials/700299038

A Phase 1b/2 Randomized, Controlled Study of AVB-S6-500 ... This is a adaptive, phase 1b/2 study is designed to assess the efficacy and safety of AVB-S6-500 in combination with pegylated liposomal doxorubicin (PLD) ...