Low-Dose Chemotherapy + Anti-Cancer Drug for Sarcoma
Palo Alto (17 mi)Overseen byCandace L Haddox
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
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 patients with advanced sarcoma.
Is the drug Pegylated Liposomal Doxorubicin Hydrochloride, Peposertib a promising treatment for sarcoma?Pegylated Liposomal Doxorubicin, also known as Doxil or Caelyx, shows promise as a treatment for sarcoma because it can deliver higher concentrations of the drug to tumors with less toxicity compared to traditional forms. It has been effective in some patients, even those with poor prognosis, and is generally well tolerated.167910
What safety data is available for the treatment using low-dose chemotherapy and anti-cancer drugs like Doxil for sarcoma?The safety data for pegylated liposomal doxorubicin (Doxil) in sarcoma indicates that it is generally well tolerated with modest toxicity. In a Phase II trial, the main limiting toxicities were mucositis and hand-foot syndrome, but no definite cardiac toxicity was observed. A randomized Phase II trial comparing Doxil to doxorubicin showed that Doxil was significantly less myelosuppressive and had fewer cases of febrile neutropenia and alopecia. The major toxicity with Doxil was skin-related, specifically palmar-plantar erythrodysesthesia. Overall, Doxil has an improved toxicity profile compared to standard doxorubicin, with reduced clinical cardiotoxicity even at cumulative doses exceeding 500 mg/m2.13469
What data supports the idea that Low-Dose Chemotherapy + Anti-Cancer Drug for Sarcoma is an effective treatment?The available research shows that pegylated-liposomal doxorubicin, a form of the drug used in Low-Dose Chemotherapy + Anti-Cancer Drug for Sarcoma, has some activity in treating sarcoma, especially in patients with poor prognosis. In a study with 47 patients, 3 experienced significant improvement, and 15 were thought to benefit from the treatment. The treatment was generally well tolerated, with mild side effects, and no serious heart-related issues were observed. However, the effectiveness was limited, and some responses took time to appear. This suggests that while the drug can be beneficial for some patients, its overall effectiveness may be modest compared to other treatments.12589
Do I need to stop taking my current medications to join the trial?The trial requires you to stop taking certain medications. You must discontinue strong inhibitors or inducers of CYP3A4/5, CYP2C9, and CYP2C19, as well as CYP3A4/5 substrates with a narrow therapeutic index, before starting the study. Proton-pump inhibitors must also be stopped at least 5 days before treatment. You can discuss with the study doctor if alternative medications can be used.
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.Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (peposertib, liposomal doxorubicin)Experimental Treatment6 Interventions
Patients receive peposertib PO BID and pegylated liposomal doxorubicin hydrochloride IV QD during treatment cycles on study. Cycles repeat every 28 days in the absence of disease progression, unacceptable toxicity or withdrawal of consent. Patients undergo CT or MRI throughout the trial. Patients also undergo blood sample collection and 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 nearbySelect from list below to view details:
Dana-Farber Cancer InstituteBoston, MA
National Cancer Institute Developmental Therapeutics ClinicBethesda, MD
M D Anderson Cancer CenterHouston, TX
University of Virginia Cancer CenterCharlottesville, VA
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
A phase II study of Doxil (liposomal doxorubicin): lack of activity in poor prognosis soft tissue sarcomas. [2022]Liposomal doxorubicin (Caelyx, Doxil) delivers doxorubicin to a tumor, but has a vastly altered pharmacology and attenuated acute and chronic toxicities. Therefore, its efficacy in soft tissue sarcomas is worth exploring.
Phase II trial of liposomal doxorubicin (Doxil) in advanced soft tissue sarcomas. [2019]To assess the objective response rate, toxicity experienced, progression-free survival, and overall survival of patients with previously untreated advanced soft tissue sarcomas treated with a liposomal doxorubicin formulation (Doxil).
Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. [2022]The indications for pegylated liposomal doxorubicin (doxil) are expanding. We, therefore, wished to assess the safety of delivering doses exceeding 500 mg/m2 of doxil to patients with solid tumors.
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]CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37 (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX, and the major toxicity with CAELYX was to the skin. Palmar-plantar erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%) patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non-haematological grade 3 and 4 toxicities were rare. Confirmed responses were observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%); with the best response being stable disease (NC) in 16 and 18 patients, respectively. The reason for the low response rate is unknown, but it may be due partly to a high proportion of gastrointestinal stromal tumours. In conclusion, CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity profile and should be considered for further investigation in combination with other agents such as ifosfamide.
Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate cancer (AIPC)--delayed response and flare phenomenon should be considered. [2019]Compared with the native drug, liposomal PEG-coated doxorubicin (Caelyx) enhances tumour activity and reduces toxicity. The formulation may therefore be beneficial in anthracycline-sensitive malignancies, where toxicity represents a major problem, as is the case in androgen-insensitive prostate cancer (AIPC).
Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. [2018]Paclitaxel and doxorubicin are among the most active chemotherapeutic agents in various types of tumors. Pegylated liposomal doxorubicin (Caelyx) has a more favorable pharmacokinetic and toxicity profile than the free drug. We conducted a phase I study to determine the maximum tolerated doses (MTD) and the dose limiting toxicities (DLT) of the combination administered every 2 weeks in patients with advanced solid tumors.
Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. [2022]Caelyx/Doxil is a novel pegylated liposomal formulation of the first-generation anthracycline, doxorubicin. The pharmacokinetics of this polyethylene-glycol-coated liposome are characterized by a reduced volume of distribution, a long intravascular circulating half-life and slow plasma clearance compared with free doxorubicin. This, coupled with a small vesicular size, uniquely promotes the localization of Caelyx/Doxil at tumor sites and explains its altered toxicity profile. The FDA and EMEA have approved its use for the treatment of AIDS-related Kaposi's sarcoma and, more recently, for recurrent epithelial ovarian cancer (EOC). Numerous investigations have focused on its use in the treatment of metastatic breast cancer, as well as recurrent squamous cell cervical carcinoma, soft tissue sarcoma, squamous head and neck cancers, prostate cancers and malignant gliomas. Ongoing clinical studies of combination regimens incorporating Caelyx/Doxil will further clarify its role in the treatment of advanced solid tumors.
Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies. [2022]Pegylated liposomal doxorubicin (PEG-LD) and gemcitabine have single-agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies.
Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. [2022]Pegylated-liposomal doxorubicin (Doxil) is a unique form of liposomal doxorubicin in which the liposomes are coated with methoxypoly (ethylene glycol), resulting in a diminished uptake by the reticuloendothelial system, leading to a longer half-life in blood and a different toxicity profile than nonpegylated liposomes. We performed a phase II study of Doxil in sarcoma. The patient population was primarily previously treated or had diagnoses considered unresponsive to chemotherapy. The initial dose per course was 55 mg/m2 every four weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Treatment was generally well tolerated. Of 214 evaluable treatment courses in 47 patients, toxicities were mild and similar to previous reports, but dose reduction was common. No definite cardiac toxicity was observed. There were: 6 osteosarcomas, 3 Ewings, 1 extraosseous osteosarcoma, 1 chondrosarcoma, 2 alveolar soft part sarcomas, 15 gastrointestinal stromal cell tumors (GIST), and 19 other soft tissue sarcomas. Three of the 47 patients received a CR or PR, although 15 of the 47 patients were felt to have derived clinical benefit from the treatment. Some responses were delayed. These data suggest that pegylated-liposomal doxorubicin has activity in this population of poor prognosis sarcoma and that this treatment is associated with modest toxicity.
Long-term cure of soft tissue sarcoma with pegylated-liposomal doxorubicin after doxorubicin and ifosfamide failure. [2022]Doxorubicin is one of the most active drugs available for the treatment of sarcoma. Pegylated-liposomal doxorubicin (PLD) is a formulation of doxorubicin in which the doxorubicin is encapsulated in liposomes coated with methoxypoly (ethylene glycol); this formulation results in decreased uptake by the reticuloendothelial system, higher concentrations of drug in tumor, and less toxicity, including reduced cardiotoxicity, nausea, alopecia, and myelosuppression. No premedication is necessary. While PLD has a better toxicity profile than free doxorubicin, there is no consensus on the relative efficacy of PLD and free doxorubicin in sarcoma.