APX005M + Doxorubicin for Soft Tissue Sarcoma

Not currently recruiting at 4 trial locations

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alexander Z. Wei, MD

Must be taking: Doxorubicin

Must not be taking: Anthracyclines, CD40 agonists, Steroids

Disqualifiers: Autoimmune, Brain metastases, Cardiac, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with advanced soft tissue sarcoma, a type of cancer. It combines doxorubicin, a standard chemotherapy drug, with APX005M, an experimental immunotherapy that may enhance doxorubicin's effects. The primary goal is to assess the safety and effectiveness of this combination. Suitable candidates include those with advanced soft tissue sarcoma that cannot be removed by surgery or treated with radiation, specifically types like dedifferentiated liposarcoma, leiomyosarcoma, or myxofibrosarcoma. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy, immunotherapy, or certain other treatments within 21 days before joining. It's best to discuss your specific medications with the trial team.

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

Research is examining the safety and effectiveness of combining a new drug, APX005M, with doxorubicin to treat advanced soft tissue sarcoma. Doxorubicin is a common treatment for this condition, while APX005M remains under study.

Previous studies have shown that patients tolerate APX005M well when combined with doxorubicin. However, doxorubicin can cause heart problems with prolonged use, so this study limits its administration to a specific number of treatment cycles.

This phase 2 trial aims to provide more information about the safety of using these two drugs together. Since doxorubicin is already approved, much is known about its safety. APX005M is still being tested, so participation in this trial contributes to understanding its safety and potential benefits for people with advanced sarcoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about APX005M in combination with Doxorubicin for treating soft tissue sarcoma because it introduces a novel approach by targeting the CD40 receptor, which plays a crucial role in activating the immune system against cancer cells. Unlike standard treatments that primarily focus on chemotherapy alone, APX005M aims to enhance the body's immune response, potentially improving the effectiveness of the treatment. Additionally, after the initial cycles, APX005M can be continued as a single agent, offering a tailored approach that might reduce the risk of cardiac toxicity associated with prolonged Doxorubicin use. This combination could offer a more comprehensive attack on the cancer with potentially fewer long-term side effects.

What evidence suggests that this treatment might be an effective treatment for soft tissue sarcoma?

Research has shown that combining APX005M with doxorubicin might enhance treatment effectiveness for advanced soft tissue sarcoma. In this trial, participants will receive both doxorubicin, a common treatment, and APX005M, an immunotherapy that may help the immune system fight cancer cells more effectively. Early studies suggest this combination could outperform doxorubicin alone. APX005M aims to boost the immune system, helping the body identify and attack cancer cells more effectively. Although this method is still under investigation, initial results appear promising for individuals with advanced sarcoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Alexander Wei, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults with advanced soft tissue sarcoma that can't be removed by surgery or cured with radiation. They should have measurable disease, no prior anthracycline chemotherapy or CD40 agonist treatment, and must not have had certain heart conditions recently. Participants need to agree to use contraception and have acceptable blood counts and organ function.

Inclusion Criteria

My disease cannot be cured with surgery or radiation.

My liposarcoma has a dedifferentiated component.

Patients must have measurable disease by RECIST criteria version 1.1

Exclusion Criteria

I don't have symptoms from brain metastases and if present, they are stable and untreated with no plans for immediate treatment.

I do not have HIV or hepatitis A, B, or C.

I haven't needed antibiotics for a serious infection in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A small number of patients are treated and monitored closely for side effects to establish a safe and tolerable dose combination

6 months

Treatment

Patients receive doxorubicin and APX005M in 21-day cycles for up to 8 cycles. Patients without disease progression or unacceptable toxicity may continue with APX005M alone.

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• APX005M
• Doxorubicin

Trial Overview The study tests the combination of APX005M (an immunotherapy drug) with doxorubicin (a standard cancer treatment) in patients with advanced sarcomas. The goal is to see if adding APX005M improves the effectiveness of doxorubicin without causing unacceptable side effects.

How Is the Trial Designed?

Group I: Doxorubicin/APX005M Experimental Treatment 2 Interventions

Patients will be treated with doxorubicin and APX005M in 21 day cycles. All patients receive the same treatment (there is no "placebo" arm). After completing 8 cycles of study treatment, patients without evidence of disease progression or unacceptable toxicity may continue treatment with APX005M alone. Doxorubicin will not be continued beyond cycle 8 due to the risk for cardiac toxicity from cumulative dosing.

Who Is Running the Clinical Trial?

Alexander Z. Wei, MD

Lead Sponsor

Trials

1

Recruited

30+

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Apexigen America, Inc.

Industry Sponsor

Trials

12

Recruited

630+

Apexigen, Inc.

Industry Sponsor

Trials

12

Recruited

630+

Published Research Related to This Trial

Pegylated liposomal doxorubicin (PLD) is generally safer than traditional doxorubicin, with fewer severe side effects like alopecia, nausea, and cardiotoxicity, making it a favorable option for treating sarcoma.

However, this case highlights a rare but serious side effect of PLD: irreversible renal failure due to thrombotic microangiopathy, which occurred in a 50-year-old man after long-term treatment, emphasizing the need for monitoring kidney function during PLD therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin-induced renal toxicity in retroperitoneal liposarcoma: a case report and literature review. Savani, M., Woerner, K., Bu, L., et al.[2021]

Aldoxorubicin, a derivative of doxorubicin, shows promise in treating advanced soft tissue sarcomas (STS) by releasing doxorubicin specifically in the acidic environment of tumors, potentially improving efficacy.

Preliminary phase 3 trial results indicate that aldoxorubicin has minimal cardiac toxicity compared to traditional doxorubicin and offers a progression-free survival advantage in patients with leiomyosarcoma and liposarcoma, although further studies are needed to confirm its role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldoxorubicin for the treatment of soft tissue sarcoma. Sachdev, E., Sachdev, D., Mita, M.[2019]

In a study of 75 patients with advanced soft tissue sarcoma treated with doxorubicin, combination therapy resulted in a better time to treatment failure (TTF) and overall response rate compared to doxorubicin monotherapy.

However, there was no significant difference in overall survival (OS) between combination therapy and monotherapy, suggesting that while combination therapy may improve short-term outcomes, it does not extend long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome for Advanced or Metastatic Soft Tissue Sarcoma of Nonextremities Treated with Doxorubicin-Based Chemotherapy: A Retrospective Study from a Single Cancer Institution. Marshall, S., Nakano, K., Sugiura, Y., et al.[2022]

In a study of 504 patients with soft-tissue sarcomas receiving doxorubicin, the incidence of significant cardiotoxicity was low, even at high cumulative doses (>450 mg/m2), suggesting that doxorubicin can be safely administered with careful monitoring.

The use of the cardioprotectant dexrazoxane did not impact the efficacy of doxorubicin treatment, indicating that it can be an effective strategy to mitigate cardiotoxic risks without compromising cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of Doxorubicin Cardiotoxicity in Patients with Advanced Soft-tissue Sarcoma Treated in the ANNOUNCE Phase III Randomized Trial. Jones, RL., Wagner, AJ., Kawai, A., et al.[2022]

In a phase II study involving 16 patients with recurrent or metastatic soft tissue sarcomas, liposomal doxorubicin (Doxil) showed no significant responses, indicating limited efficacy in this specific patient population.

Despite the lack of effectiveness, Doxil was well tolerated, with no grade 4 toxicities and only a few instances of grade 3 toxicities, suggesting a favorable safety profile for future studies in different patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of Doxil (liposomal doxorubicin): lack of activity in poor prognosis soft tissue sarcomas. Garcia, AA., Kempf, RA., Rogers, M., et al.[2022]

In a study of 2045 patients with advanced soft tissue sarcoma, 36.6% completed 6 cycles of doxorubicin-based chemotherapy without disease progression, with a median overall survival of 15.7 months after treatment.

The study provides crucial data on progression-free survival (4.2 months) and overall survival (15.7 months) after 6 cycles of doxorubicin, which is essential for designing future studies aimed at improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival of soft tissue sarcoma patients after completing six cycles of first-line anthracycline containing treatment: an EORTC-STBSG database study. Verschoor, AJ., Litière, S., Marréaud, S., et al.[2022]

ALGP-doxorubicin (ALGP-doxo) demonstrated significantly higher antitumoral efficacy compared to standard doxorubicin in patient-derived xenograft models of synovial sarcoma and dedifferentiated liposarcoma, leading to tumor shrinkage and stabilization.

The prodrug ALGP-doxo was well-tolerated at doses 30- to 40-fold higher than doxorubicin, with no significant adverse events reported, suggesting it may be a safer alternative for treating soft tissue sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Antitumoral Efficacy of PhAc-ALGP-Doxorubicin, an Enzyme-Activated Doxorubicin Prodrug, in Patient-Derived Soft Tissue Sarcoma Xenograft Models. Cornillie, J., Wozniak, A., Pokreisz, P., et al.[2020]

The IVADo regimen, which combines doxorubicin with ifosfamide, vincristine, and actinomycin D, showed a 76% response rate in treating pediatric soft tissue sarcoma, indicating its efficacy in reducing tumor volume.

While the treatment was effective, it also resulted in significant toxicity, particularly myelosuppression, with 67% of cycles causing Grade 4 neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IVADo regimen--a pilot study with ifosfamide, vincristine, actinomycin D, and doxorubicin in children with metastatic soft tissue sarcoma: a pilot study of behalf of the European pediatric Soft tissue sarcoma Study Group. Bisogno, G., Ferrari, A., Bergeron, C., et al.[2022]

In a trial involving 94 patients with advanced soft-tissue sarcoma, CAELYX (pegylated liposomal doxorubicin) demonstrated a significantly lower incidence of severe myelosuppression and alopecia compared to standard doxorubicin, indicating a better safety profile.

Both CAELYX and doxorubicin showed similar antitumor activity, with response rates of 10% and 9% respectively, suggesting that CAELYX is a viable alternative for treatment with reduced toxicity, warranting further investigation in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group. Judson, I., Radford, JA., Harris, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03719430

APX005M and Doxorubicin in Advanced Sarcoma The investigators believe that doxorubicin, which is currently the standard of care for most advanced sarcomas, could work better when combined with APX005M, ...

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03719430/

Clinical Trial: NCT03719430 This study will assess the safety and efficacy of combining APX005M, a novel immunomodulatory drug, together with standard of care doxorubicin, ...

3. trial.medpath.com trial.medpath.com/clinical-trial/5f6e7ff727b89968/nct03719430-phase-ii-trial-apx005m-cd40-antibody-doxorubicin-sarcomas

APX005M and Doxorubicin in Advanced Sarcoma - MedPath This study will assess the safety and efficacy of combining APX005M, a novel immunomodulatory drug, together with standard of care doxorubicin, for the ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-00103

APX005M and Doxorubicin in Treating Patients with ... This phase II trial studies how well APX005M works when given together with standard of care doxorubicin in treating patients with soft tissue sarcoma that ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8678134/

Improving Immunotherapy Efficacy in Soft-Tissue Sarcomas Anti-PD-(L)1 therapies yield a disappointing response rate of 15% across soft-tissue sarcomas, even if some subtypes benefit more than others.

6. researchgate.net researchgate.net/publication/339147497_A_phase_II_trial_with_safety_lead-in_to_evaluate_the_addition_of_APX005M_a_CD40_agonistic_monoclonal_antibody_to_standard-of-care_doxorubicin_chemotherapy_for_the_treatment_of_advanced_soft_tissue_sar?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJzY2llbnRpZmljQ29udHJpYnV0aW9ucyIsInByZXZpb3VzUGFnZSI6bnVsbCwic3ViUGFnZSI6bnVsbH19

A phase II trial with safety lead-in to evaluate the addition of ... A phase II trial with safety lead-in to evaluate the addition of APX005M, a CD40 agonistic monoclonal antibody, to standard-of-care doxorubicin ...