Low-Dose Chemotherapy + Anti-Cancer Drug for Sarcoma

Recruiting in Palo Alto (17 mi)

+12 other locations

Overseen by Candace L Haddox

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP inhibitors, CYP inducers, PPIs

Disqualifiers: Uncontrolled illness, Active brain metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of combination therapy with liposomal doxorubicin and peposertib in treating patients with sarcoma that has spread from where it first started, to other places in the body (metastatic), or cannot be removed by surgery (unresectable) and for which no known cure is available (advanced). Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects and work better than other forms of the drug. Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also enhance the activity of chemo- and radiotherapy. There is some pre-clinical evidence in animal models that combining peposertib with liposomal doxorubicin can shrink or stabilize certain types of cancer for longer than either drug alone, but it is not known if this will happen in people. Combination therapy with liposomal doxorubicin and peposertib may be effective in treating patients with advanced sarcoma.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically those that are strong inhibitors or inducers of certain liver enzymes (CYP3A4/5, CYP2C9, and CYP2C19) and proton-pump inhibitors (PPIs). You should discuss with the study doctor to see if alternative medications can be used.

What data supports the effectiveness of the drug Pegylated Liposomal Doxorubicin Hydrochloride (Doxil) for treating sarcoma?

Research shows that Pegylated Liposomal Doxorubicin (Doxil) has some activity in treating sarcoma, with a few patients experiencing clinical benefits and modest side effects, although responses can be delayed. ^{1 2 3 4 5}

Is the combination of low-dose chemotherapy and anti-cancer drug generally safe for humans?

The treatment using pegylated liposomal doxorubicin (also known as Doxil, Caelyx) has been generally well tolerated in humans, with mild toxicities like skin reactions and less severe blood-related side effects compared to standard doxorubicin. No significant heart-related issues were observed, even at higher doses. ^{1 3 6 7 8}

What makes the drug Pegylated Liposomal Doxorubicin Hydrochloride unique for treating sarcoma?

Pegylated Liposomal Doxorubicin Hydrochloride is unique because it uses a special coating to stay in the bloodstream longer, allowing more of the drug to reach the tumor with less toxicity, especially to the heart, compared to traditional doxorubicin. ^{1 3 6 9 10}

Research Team

Candace L Haddox

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

Adults with advanced sarcoma that has spread or can't be surgically removed, who have tried at least one treatment but not exceeded a certain dose of anthracycline. They must have acceptable organ function and performance status, no severe cardiac issues, and agree to use contraception. Excludes those with unresolved toxic effects from previous cancer treatments (except hair loss), recent radiation therapy, taking certain drugs affecting liver enzymes or proton-pump inhibitors without stopping them first.

Inclusion Criteria

My sarcoma cannot be surgically removed, has spread, and cannot be cured.

Absolute neutrophil count >= 1,500/mcL

I am 18 years old or older.

Exclusion Criteria

I had palliative radiotherapy over 2 weeks ago and any side effects have resolved.

Patients who are receiving any other investigational agents

I have recovered from side effects of previous cancer treatments, except for hair loss.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive peposertib orally twice daily and pegylated liposomal doxorubicin intravenously once daily during 28-day cycles

28 days per cycle

Regular visits for CT/MRI and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

Dose Escalation

Evaluation of safety and tolerability to determine the recommended phase 2 dose

Up to 28 days

Dose Expansion

Further assessment of adverse events and pharmacokinetics at the selected dose

Up to 1 year

Treatment Details

Interventions

• Pegylated Liposomal Doxorubicin Hydrochloride (Anti-tumor antibiotic)
• Peposertib (Other)

Trial Overview The trial is testing the combination of low-dose liposomal doxorubicin (a chemotherapy drug) with peposertib (an anti-cancer drug) in adults with advanced sarcoma. The study aims to find the safest doses, understand side effects better, and see how effective this combo is against cancer that's hard to treat.

Participant Groups

Group I: Treatment (peposertib, liposomal doxorubicin) Experimental Treatment 6 Interventions

Patients receive peposertib PO BID on days 1-28 of each cycle and liposomal doxorubicin IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity or withdrawal of consent. Patients undergo blood sample collection, and CT or MRI throughout the trial. Patients also undergo tissue biopsy during screening and on the trial.

Pegylated Liposomal Doxorubicin Hydrochloride is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Doxil for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

🇪🇺 Approved in European Union as Caelyx for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma
• Breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Siteman Cancer Center-South County Saint Louis, MO

Dana-Farber Cancer Institute Boston, MA

National Cancer Institute Developmental Therapeutics Clinic Bethesda, MD

M D Anderson Cancer Center Houston, TX

More Trial Locations

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14080

Patients Recruited

41,180,000+

Findings from Research

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies. Fracasso, PM., Blum, KA., Tan, BR., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. Skubitz, KM.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas. Chidiac, T., Budd, GT., Pelley, R., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate cancer (AIPC)--delayed response and flare phenomenon should be considered. Fosså, SD., Vaage, S., Letocha, H., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. Mavroudis, D., Kouroussis, Ch., Kakolyris, S., et al.[2018]

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 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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure. Savani, M., Murugan, P., Skubitz, KM.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Tejada-Berges, T., Granai, CO., Gordinier, M., 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. United States pubmed.ncbi.nlm.nih.gov

Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies. [2022]

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

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. [2022]

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

Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas. [2019]

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

Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate cancer (AIPC)--delayed response and flare phenomenon should be considered. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. [2018]

7. 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]

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. England pubmed.ncbi.nlm.nih.gov

Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure. [2022]

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

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. [2022]