Clinical Trials /

Study of DCC-3014 in Combination With Avelumab in Patients With Advanced or Metastatic Sarcomas

NCT04242238

Description:

This study is being done to find the safest dose of DCC-3014 that can be given with avelumab to participants with advanced or metastatic sarcomas that will not cause serious side effects.

Related Conditions:
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of DCC-3014 in Combination With Avelumab in Patients With Advanced or Metastatic Sarcomas
  • Official Title: A Phase 1b Dose Escalation and Dose Expansion Study of a CSF1R Inhibitor (DCC-3014) Administered Concurrently With an Anti-PD-L1 Antibody (Avelumab) in Patients With Advanced High-grade Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: 19-340
  • NCT ID: NCT04242238

Conditions

  • Sarcoma
  • Advanced Sarcoma
  • High Grade Sarcoma

Interventions

DrugSynonymsArms
DCC-3014Advanced High-grade Sarcoma
AvelumabAdvanced High-grade Sarcoma

Purpose

This study is being done to find the safest dose of DCC-3014 that can be given with avelumab to participants with advanced or metastatic sarcomas that will not cause serious side effects.

Trial Arms

NameTypeDescriptionInterventions
Advanced High-grade SarcomaExperimentalDose Escalation: First 18 pts with locally advanced or metastatic high-grade sarcomas Dose Expansion: 10 pts per each diagnosis - undifferentiated pleomorphic sarcoma or myxofibrosarcoma, Leiomyosarcoma, Dedifferentiated liposarcoma
  • DCC-3014
  • Avelumab

Eligibility Criteria

        Inclusion Criteria:

          -  Age >/= 18 years at the time of informed consent

          -  Be capable, willing, and able to provide written informed consent/assent

          -  Be willing to comply with clinical trial instructions and requirement, including
             mandatory biopsies

          -  Dose escalation phase: Patients must have a histologically confirmed metastatic and/or
             locally advanced high grade sarcoma

          -  Dose expansion phase: Patients must have a histologically confirmed metastatic and/or
             locally undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, or
             dedifferentiated liposarcoma

          -  Adequate performance status: ECOG 0 or 1/KPS 100-70%

          -  Patients must have at least one prior line of systemic therapy (e.g. chemotherapy,
             immunotherapy, targeted or biological therapy) for their sarcoma. Prior neoadjuvant
             and/or adjuvant therapy will count regardless of when it was completed. Treatment
             naïve patients can enroll if they refuse standard of care systemic chemotherapy.

          -  Presence of measurable disease per RECIST v1.1. Target lesions must not be chosen from
             a previously irradiated field unless there has been radiographically and/or
             pathologically documented tumor progression in that lesion prior to enrollment

          -  Adequate organ function determined within 28 days of treatment initiation, as defined
             in Table 3:

        Table 3: Laboratory values inclusion criteria

        Hematological Absolute neutrophil count (ANC): ≥1,500 / mcL Platelets: ≥ 100,000 / mcL
        Hemoglobin: ≥ 9 g/dL or ≥ 5.6 mmol/L

        Renal

        Serum Creatinine OR Measured or calculated (Creatinine clearance should be calculated per
        institutional standard) creatinine clearance (GFR can also be used in place of creatinine
        or CrCl):

        ≤ 1.5 x upper limit of normal (ULN) OR ≥ 60 mL/min for patient with creatinine levels > 1.5
        x institutional ULN

        Hepatic Serum total bilirubin: ≤ 1.5 x ULN OR Direct bilirubin ≤ ULN for patients with
        total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT): ≤ 2.5 x ULN OR ≤ 5 x ULN for
        patient with liver metastases Albumin: ≥ 2.5mg/dL

        Coagulation Internalized Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 x ULN
        unless patient is receiving anticoagulant therapy as long as PT or PTT is within
        therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time
        (aPTT): ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT
        is within therapeutic range of intended use of anticoagulants

          -  Women of childbearing potential (defined as a sexually mature female who has not
             undergone a hysterectomy or bilateral oophorectomy or who has not been naturally
             postmenopausal for at least 24 consecutive months) must have a negative urine or serum
             pregnancy test at screening at ≤ 72 hours prior to day 1 of study treatment. If the
             urine pregnancy test if positive or cannot be confirmed as negative, a serum pregnancy
             test will be required

          -  Male and female patients of childbearing potential must be willing to use a highly
             effective method of contraception, for the course of the study through 7 months after
             the last dose of study medication. Abstinence is acceptable if this is the usual
             lifestyle and preferred contraception for the patient

        Exclusion Criteria:

          -  History of unstable or deteriorating cardiovascular disease within the previous 6
             months prior to screening including but not limited to the following:

               -  Unstable angina or myocardial infarction

               -  CVA/stroke

               -  Congestive heart failure (New York Heart Association [NYHA] Class III or IV)

               -  Uncontrolled clinically significant arrhythmias

          -  Evidence or clinically significant interstitial lung disease or active, noninfectious
             pneumonitis related to prior immunotherapy treatment

          -  Malabsorption syndrome or other illness that could affect oral absorption

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Patients with previously treated brain metastases or carcinomatous
             meningitis may participate provided they are stable (without evidence of progression
             by imaging for at least four weeks prior to the first dose of trial treatment and any
             neurologic symptoms have returned to baseline), have no evidence of new or enlarging
             brain metastases, and are not using steroids for at least 7 day prior to trial
             treatment

          -  Current use of immunosuppressive medication, EXCEPT for the following:

               -  intranasal, inhaled, topical steroids, or local steroid injection (e.g.,
                  intra-articular injection)

               -  Systemic corticosteroids at physiologic doses </= 10mg/day of prednisone or
                  equivalent

               -  Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication)

          -  Evidence of clinically significant immunosuppression such as the following:

               -  Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease

               -  Concurrent opportunistic infection

               -  Receiving systemic immunosuppressive therapy (>2 weeks) including oral steroid
                  doses > 10mg/day of prednisone or equivalent within 2 months prior to enrollment

          -  History or evidence of symptomatic autoimmune disease (e.g., pneumonitis,
             glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
             that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive
             drugs or biological agents used for treatment of autoimmune diseases) in past 2 years
             prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin
             for diabetes or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency) is not considered a form of systemic treatment for autoimmune
             disease

          -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) disease that
             is not controlled

          -  Patients known to be positive for active Hepatitis B (HBsAg reactive with detectable
             HBV DNA), or Hepatitis C (HCV RNA (qualitative) is detected)

             ° Patients with chronic hepatitis B (positive HBsAg and/or HBcAb and negative HBV DNA
             by PCR) are eligible for this study if deemed safe by a gastroenterologist

          -  Prolonged QTcF > 450 ms for men and >470 ms for women at Screening

          -  Patients who have received a live vaccine within 30 days of the start date of the
             planned 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

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 3 weeks prior to study
             Day 1 or who has not recovered (i.e., </= Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., </= Grade 1 or at
             baseline) from adverse events due to a previously administered agent

               -  Note: Alopecia, neuropathy Grade </= 2, or other Grade </= not constituting a
                  safety risk based on investigator's judgment are acceptable

               -  Note: If patient received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting therapy
                  events due to a previously administered agent

          -  Women who are pregnant or breast feeding

          -  Patients expecting to conceive or father children within the projected duration of the
             trial, starting with the pre-screening or screening visit through 120 days after the
             last dose of study treatment(s)

          -  Prior organ transplantation including allogenic stem-cell transplantation

          -  Active infection requiring systemic therapy

          -  Known prior severe hypersensitivity to investigational product or any component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies (NCI CTCAE v4.03 Grade >/= 3)

          -  Other severe acute or chronic medical conditions including immune colitis,
             inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
             conditions including recent (within the past year) or active suicidal ideation or
             behavior; or laboratory abnormalities that may increase the risk associated with study
             participation or study treatment administration or may interfere with the
             interpretation of study results and, in the judgment of the investigator, would make
             the patient inappropriate for entry into this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose
Time Frame:1 year
Safety Issue:
Description:Identify the maximum tolerated dose (MTD) by evaluating toxicity using NCI CTCAE (version 4.03)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Advanced High Grade Sarcoma
  • CSF1R Inhibitor
  • DCC-3014
  • Anti-PD-L1 Antibody
  • Anti-PD-L1
  • Avelumab
  • Memorial Sloan Kettering Cancer Center
  • 19-340

Last Updated

January 23, 2020