Clinical Trials /

APX005M and Doxorubicin in Advanced Sarcoma

NCT03719430

Description:

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.

Related Conditions:
  • Dedifferentiated Liposarcoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: APX005M and Doxorubicin in Advanced Sarcoma
  • Official Title: A Phase II Trial Evaluating APX005M (a CD40 Agonistic Monoclonal Antibody) in Combination With Standard-of-Care Doxorubicin for the Treatment of Advanced Sarcomas

Clinical Trial IDs

  • ORG STUDY ID: AAAS0095
  • NCT ID: NCT03719430

Conditions

  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
DoxorubicinADRIAMYCINDoxorubicin/APX005M
APX005MAPX-005MDoxorubicin/APX005M

Purpose

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.

Detailed Description

      Doxorubicin, a chemotherapy, is currently considered standard-of-care treatment for most
      advanced soft tissue sarcomas. This study will assess the safety and efficacy of combining
      APX005M, a novel immunomodulatory drug, together with standard of care doxorubicin, for the
      treatment of patients with advanced soft tissue sarcoma. APX005M is an agonistic monoclonal
      antibody targeting the CD40 receptor and may have favorable effects on certain types of
      immune cells in sarcoma tumors, particularly macrophages.

      The primary objective is to determine the objective response rate. Secondary objectives
      include further evaluation of safety and efficacy. A subset of patients will undergo tumor
      biopsies at baseline and while on study treatment to help understand how the drug combination
      works and to evaluate how the composition of immune cells in the tumor changes after the
      treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Doxorubicin/APX005MExperimentalPatients 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.
  • Doxorubicin
  • APX005M

Eligibility Criteria

        Inclusion Criteria

          1. Histologically confirmed advanced soft tissue sarcoma for which doxorubicin treatment
             is considered appropriate. Patients with well-differentiated liposarcoma who have
             histologic evidence of a dedifferentiated component are eligible. Kaposi sarcoma and
             gastrointestinal stromal tumor (GIST) are not eligible.

          2. Disease must be locally advanced and unresectable or metastatic (that is, considered
             not amenable to curative surgery or radiation).

          3. Patients must have measurable disease by RECIST criteria version 1.1.

          4. Patients must demonstrate an ECOG performance status of 0 or 1 and be considered an
             appropriate candidate for anthracycline chemotherapy. There is no limit on prior lines
             of systemic therapy received. Treatment naïve patients may be enrolled.

          5. Acceptable laboratory parameters:

               -  Absolute neutrophil count (ANC) ≥ 1,500/mm3

               -  Hemoglobin ≥ 9 g/dL

               -  Platelets ≥ 100,000/mm3

               -  Creatinine ≤ 1.5 times upper limit of normal OR Calculated creatinine clearance >
                  45 mL/min

               -  Total bilirubin ≤ upper limit of normal

               -  AST/ALT ≤ 1.5 times upper limit of normal

          6. Patients must have normal left ventricular systolic function, as demonstrated by a
             transthoracic echocardiogram or MUGA scan at screening, showing a normal left
             ventricular ejection fraction as defined by the laboratory performing the test.

          7. Women of child-bearing potential and all men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) prior to study entry and for
             the duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol must
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and for 4 months after completion of study drug administration.

          8. Ability to understand and willingness to sign a written informed consent document.

          9. After the safety lead-in phase is complete, the next consecutive 10 patients enrolled
             on the study must have a site of tumor tissue which is amenable to image-guided biopsy
             by interventional radiology with at most minimal risk to the patient. These 10
             patients will be required to undergo tumor biopsy at screening and while on-treatment.

        Exclusion Criteria

          1. Patients must not have received treatment with any chemotherapy, immunotherapy,
             radiotherapy or an investigational agent for malignancy within the 21 days preceding
             registration. Patients may not have received treatment with a small molecule targeted
             anti-cancer agent within 14 days preceding study registration, provided this
             represents at least 7 half-lives for that agent. Furthermore, toxic effects from any
             prior therapy (except alopecia) must have resolved to ≤ grade 1 by NCI CTCAE v 5.0 or
             to the patient's baseline by registration.

          2. Patients may not be receiving any other investigational agent for any purpose.

          3. Patients may not have received prior treatment with:

               -  any anthracycline chemotherapy

               -  CD40 agonist

          4. Patients may not have received prior radiotherapy of the mediastinal or pericardial
             area or whole pelvis radiation.

          5. Patients may not have active, known or suspected autoimmune disease with the
             exceptions of well-controlled: asthma or allergic rhinitis, vitiligo, type 1 diabetes
             mellitus, psoriasis, or hypothyroidism.

          6. Patients may not be receiving chronic systemic steroid therapy in excess of
             physiologic/ replacement doses (prednisone ≤ 10 mg/day is acceptable), or on any other
             form of immunosuppressive medication for 14 days prior to registration.

          7. Patients with symptomatic brain metastases may not be enrolled. Those subjects with
             untreated brain metastases ≤ 1 cm who are asymptomatic and for whom there are no plans
             for surgery, radiation or corticosteroid use may be considered eligible at the
             discretion of the principal investigator. Subjects with brain metastases that have
             been treated and are stable for at least 30 days are eligible if asymptomatic and not
             receiving corticosteroids. Screening for brain metastases is not required and should
             not be routinely pursued given their uncommon incidence in sarcoma.

          8. Patients may not have:

               -  uncontrolled intercurrent illness including, but not limited to congestive heart
                  failure, unstable angina pectoris, uncontrolled cardiac arrhythmias, uncontrolled
                  diabetes mellitus or uncontrolled psychiatric illness that would limit compliance
                  with study requirements in the opinion of the investigator.

               -  unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction
                  within 6 months of registration.

               -  any thromboembolic event within 1 month prior to registration

               -  any active coagulopathy

               -  any clinically serious, active infection requiring treatment with antibiotics
                  within 14 days prior to registration

               -  major surgery within 28 days of registration.

          9. Patients may not have history of another primary cancer, with the exception of:

               -  curatively treated non-melanomatous skin cancer,

               -  curatively treated cervical carcinoma in-situ,

               -  other primary cancers treated with curative intent, no known active disease and
                  no treatment administered within 2 years prior to registration.

               -  other cancers considered indolent and for which no treatment is anticipated, in
                  the opinion of the principal investigator

         10. Patients may not be pregnant or nursing.

         11. Patients may not have known HIV or hepatitis A, B or C infection; however, screening
             tests for these infections are not required.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:6 months
Safety Issue:
Description:The percentage of patients achieving a partial or complete response as measured by imaging assessments from study treatment

Secondary Outcome Measures

Measure:Recommended Dose Combination for APX005M and Doxorubicin and Combination Treatment
Time Frame:6 months
Safety Issue:
Description:A safety-lead in phase will be conducted during which a small number of patients will be treated and monitored closely for certain side effects. If these side effects are seen, the dose of doxorubicin will be adjusted and the study treatment reassessed among another small number of patients. The purpose of the safety lead-in phase is to establish a safe and tolerable dose combination ("the recommended dose") which will be used during the remainder of the study.
Measure:Evaluation of Side Effects from APXO05M and Doxorubicin Treatment
Time Frame:18 months
Safety Issue:
Description:Patients on the study will be assessed at regular intervals during clinical visits and through laboratory testing to monitor side effects from the study treatment.
Measure:Progression Free Survival
Time Frame:18 months
Safety Issue:
Description:The mean time to either disease progression or death, whichever comes first, for patients on the study

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Columbia University

Trial Keywords

  • Leiomyosarcoma
  • Liposarcoma
  • Pleomorphic sarcoma
  • Synovial sarcoma
  • Malignant peripheral nerve sheath tumor
  • Spindle cell sarcoma

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