Weekly low-dose doxorubicin for older adults with advanced leiomyosarcoma

A Phase II Study on Efficacy and Tolerability of Weekly Doxorubicin in Elderly Patients With Advanced or Metastatic Leiomyosarcoma of Soft Tissue

This trial will test whether giving doxorubicin at a lower dose once a week helps people aged 65–100 with advanced or metastatic leiomyosarcoma keep their cancer from getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 65 Years to 100 Years
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: chemotherapy, radiation, doxorubicin
• Locations: 1 site (Aurora, Colorado)
• Trial ID: NCT07125183 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm Phase 2 trial enrolls up to 30 patients to obtain 20 evaluable older adults with unresectable or metastatic leiomyosarcoma. Participants receive doxorubicin 25 mg/m2 by bolus on days 1 and 8 of a 21-day cycle with dexrazoxane pre-treatment and pegfilgrastim on day 9 for up to eight cycles. The primary endpoint is progression-free survival rate at 12 weeks, with secondary endpoints including 6-month PFS, RECIST response rate, duration of response, overall survival, adverse events, and quality of life. A time-to-event Bayesian optimal Phase 2 design includes an interim futility look after 10 evaluable patients and correlative blood and tumor biopsies to explore immune changes.

Who should consider this trial

Good fit: Ideal candidates are people aged 65–100 with histologically confirmed advanced or metastatic leiomyosarcoma who have received 0–4 prior systemic therapies, no prior anthracycline exposure, and are medically able to receive weekly doxorubicin and protocol biopsies.

Not a fit: Patients with prior anthracycline exposure, significant cardiac or other comorbidities that preclude anthracycline use, non-leiomyosarcoma histologies, or those unable to travel to the study site are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could offer older patients similar cancer control with fewer severe side effects and improved quality of life compared with standard dosing.

How similar studies have performed: Prior clinical reports and retrospective series suggest lower, more frequent doxorubicin dosing can preserve anti-tumor activity with less toxicity, but prospective geriatric-focused data remain limited.

Eligibility criteria

Inclusion Criteria:

1. Provision to sign and date the consent form.
2. Stated willingness to comply with all study procedures and be available for the duration of the study.
3. Be male or female aged 65-100 years at the time of signing informed consent.
4. Have a histological diagnosis of advanced or metastatic soft tissue leiomyosarcoma (LMS) (by local pathology review), not curable by surgery, for which treatment with weekly doxorubicin is deemed appropriate by the investigator.
5. Have measurable or non-measurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors. Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented, or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy.
6. Have received 0 to 4 prior systemic therapies for metastatic sarcoma and NO prior anthracyclines. Re-treatment with the same drug or regimen after interruption (i.e. chemotherapy holiday) is not considered a new line of treatment, and those patients are eligible.
7. Adequate organ function
8. ECOG performance status of 0, 1 or 2.
9. Patients must consent and be willing to undergo tumor core needle biopsies at two time points: 1. Baseline, 2. Cycle 2 Day 1 (+/- 7 days); a third biopsy for off-study/progression is optional but advised. At least one tumor site must be amenable to biopsy in the judgment of the interventional radiologist and/or inverstigator.
10. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Prior history of vasectomy does NOT replace requirement for contraceptive use.
11. Female subjects will be post-menopausal as evidenced by cessation of menses for a minimum of 2 years. Prior hysterectomy or bilateral oophorectomy is also permissible.
12. Subjects must either possess or undergo placement of central venous catheter, including pheresis or trifusion catheter, PICC line, or port.

Exclusion Criteria:

1. Prior therapy with anthracycline.
2. Hypersensitivity to doxorubicin or any excipients.
3. Patients may not be receiving any other investigational agents (within 28 days prior to Cycle 1, Day 1).
4. Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 21 days prior to Cycle 1, Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 21 days earlier. Subjects with ≤ Grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study.

   Note: If a subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
5. Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
6. Patients with underlying immune deficiency, chronic infections including hepatitis, and known history of HIV or tuberculosis (TB).
7. Patients with underlying hematologic issues including bleeding diathesis, such as known previous GI bleeding requiring intervention within the past 6 months. Newly diagnosed pulmonary emboli or deep venous thrombosis must be clinically stable on anticoagulation regimen for ≥ 2 weeks as of Cycle 1 Day 1.
8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Subjects with previously treated brain metastases may participate provided they are stable based on the following: 1) MRI brain obtained during screening evaluations shows no radiographic evidence of progression or new lesions, 2) any neurologic symptoms have returned to baseline. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. Patients without a known history of brain metastases do not require screening brain MRI prior to study enrollment.
9. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
10. Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
11. Prolonged QTc interval on Screening EKG \>475 ms.
12. Left Ventricular Ejection Fraction \<50% by 2D ECHO or MUGA scan at Screening.
13. Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment, including NYHA Class II or greater heart disease.

Where this trial is running

Aurora, Colorado

• University Of Colorado Hospital — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Breelyn Wilky, MD — University of Colorado, Denver
• Study coordinator: Chelsey Cartwright

Conditions Sarcoma; Metastatic Sarcoma; Advanced Sarcoma; leiomyosarcoma; doxorubicin; geriatric