APX005M + Doxorubicin for Soft Tissue Sarcoma

Recruiting at 3 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

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II clinical trial will evaluate the safety and efficacy of adding APX005M (a CD40 agonistic monoclonal antibody) to doxorubicin for the treatment of patients with advanced soft tissue sarcoma. The investigators believe that doxorubicin, which is currently the standard of care for most advanced sarcomas, could work better when combined with APX005M, which is a type of immunotherapy.

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.

What data supports the effectiveness of the drug APX005M + Doxorubicin for treating soft tissue sarcoma?

Doxorubicin is a standard first-line treatment for soft tissue sarcoma, but its effectiveness is limited, and combination therapies have not shown significant improvements in survival. However, a study on a doxorubicin prodrug showed promising results in reducing tumor size in models, suggesting potential for more effective treatments. ^{1 2 3 4 5}

What safety data exists for APX005M + Doxorubicin in humans?

Doxorubicin, a common drug for treating soft tissue sarcoma, is known for its potential heart-related side effects (cardiotoxicity). However, a special form called pegylated liposomal doxorubicin (PLD) has a better safety profile, causing fewer heart issues but may lead to skin problems and, in rare cases, kidney issues. Aldoxorubicin, another variant, shows minimal heart toxicity, making it a safer option compared to regular doxorubicin. ^{1 6 7 8 9}

What makes the drug combination of APX005M and Doxorubicin unique for treating soft tissue sarcoma?

The combination of APX005M and Doxorubicin is unique because it potentially enhances the effectiveness of Doxorubicin, a standard treatment for soft tissue sarcoma, by adding APX005M, which may work through a different mechanism to improve outcomes. This approach aims to address the limited efficacy and high toxicity of traditional Doxorubicin treatments. ^{1 2 5 10 11}

Research Team

Alexander Wei, MD

Principal Investigator

Columbia University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

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

A phase II study of Doxil (liposomal doxorubicin): lack of activity in poor prognosis soft tissue sarcomas. [2022]

2. England 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. [2022]

3. Egypt pubmed.ncbi.nlm.nih.gov

Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. [2022]

4. United States 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. [2022]

5. United States 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. [2020]

6. United States 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. [2022]

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

Pegylated liposomal doxorubicin-induced renal toxicity in retroperitoneal liposarcoma: a case report and literature review. [2021]

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

Aldoxorubicin for the treatment of soft tissue sarcoma. [2019]

9. England 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. [2022]

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

Aldoxorubicin in soft tissue sarcomas. [2019]

11. Egypt 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. [2022]