Trastuzumab Deruxtecan for the Treatment of HER2+ Newly Diagnosed or Recurrent Osteosarcoma

B
Brian Weiss

Primary Investigator

Enrolling By Invitation
12-39 years
All
Phase 2
27 participants needed
1 Location

Brief description of study

What is the purpose of this study?
This phase II trial studies the effects of trastuzumab deruxtecan in treating patients with HER2 positive osteosarcoma that is newly diagnosed or has come back (recurrent). Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

PRIMARY OBJECTIVE:
I. To estimate the proportion of patients with recurrent measurable osteosarcoma treated withuzumab deruxtecan (DS-8201a) who are event free (%EF) at 24 weeks.
SECONDARY OBJECTIVES:
I. To assess the safety of DS-8201a in patients with recurrent osteosarcoma. II. To describehe pharmacokinetics of DS-8201a in patients with recurrent osteosarcoma.
III. To estimate the objective response rate (ORR), event free survival (EFS), overallurvival (OS) and duration of response (DOR) of patients with recurrent, measurable.
EXPLORATORY OBJECTIVES:
I. To describe the relationship between potential biomarkers and response to DS-8201a.
II. To evaluate quantitative circulating tumor deoxyribonucleic acid (DNA) (ctDNA) andulating tumor cells (CTCs) as a surrogate markers of response in recurrent osteosarcoma.

What will happen during the study?
  • Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1. Treatment repeats every 21 days for 35 cycles in the absence of disease progression or unacceptable toxicity.
  • After completion of study treatment, patients are followed up at 6 months.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Osteosarcoma, Recurrent Osteosarcoma, Riley
  • Age: Between 12 Years - 39 Years
  • Gender: All

Inclusion Criteria:
  • Patients must be > 12 years and =< 39 years of age at the time of study enrollment
  • Patients must have had histologic verification of osteosarcoma at original diagnosis
    • Patients with diagnoses of osteosarcoma and confirmed HER2 expression of > 10% ofgible for the intervention
      • Note: There is a mandatory tissue submission for HER2 staining during thegibility Screening process. Metastatic tissue, when possible fromhe most recent relapse, is strongly preferred for HER2 staining overhival tissue from primary resection or diagnostic biopsy. The evaluationd for HER2 staining to determine eligibility for therapy will be lesshan 4 weeks from screening enrollment
  • Patients must have measurable disease according to Response Evaluation Criteria in
    Solid Tumors (RECIST) 1.1. Patients with clinically inactive brain metastases may beuded in the study. Patients with treated brain metastases that are no longerymptomatic and who require no treatment with corticosteroids or anticonvulsants maybe included in the study if they have recovered from the acute toxic effect ofdiotherapy. Lastly, patient must have unresectable lesions or lesions with nourgically remove in the 6 months following enrollment
  • Patient's current disease state must be one for which they have received at leastdard initial therapy, defined as systemic therapy combined with either radiationurgery for local control of the primary tumor at diagnosis. Prior therapy afterquired
  • Patients must have a performance status corresponding to Eastern Cooperative OncologyGroup (ECOG) scores of 0 or 1. Use Karnofsky for patients > 16 years of age and Lansky=< 16 years of age. Patients who are non-ambulatory as a result of priorurgical treatment for osteosarcoma should be considered ambulatory for the purposesg performance status
  • Patients must have recovered from the acute toxic effects of all prior anti-cancerherapy and must meet the following minimum duration from prior anti-cancer directedherapy prior to enrollment. If after the required timeframe, the numericalgibility criteria are met, e.g., blood count criteria, the patient is considered tohave recovered adequately
    • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:For agents not listed, the duration of this interval must be discussed with theudy chair and the study-assigned Research Coordinator prior to enrollment
      • >= 21 days after the last dose of myelosuppressive chemotherapy (42 days ifurea)
    • Anti-cancer agents not known to be myelosuppressive (e.g., not associated with
      reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after thedose of agent
    • Antibodies: >= 4 weeks (28 days) must have elapsed from infusion of last dose ofbody, and toxicity related to prior antibody therapy must be recovered tograde =< 1
    • Corticosteroids
    • Hematopoietic growth factors: >= 14 days after the last dose of a long-actinggrowth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. Forgents that have known adverse events occurring beyond 7 days afterdministration, this period must be extended beyond the time during which adversevents are known to occur
    • Interleukins, interferons and cytokines (other than hematopoietic growth): >= 21 days after the completion of interleukins, interferon orytokines (other than hematopoietic growth factors)
    • Stem cell Infusions (with or without total body irradiation [TBI]):
      • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stemusion including donor lymphocyte infusion (DLI) or boost infusion:>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
      • Autologous stem cell infusion including boost infusion: >= 30 days
    • Vellular therapy: >= 30 days after the completion of any type of cellular therapy
      (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
    • Radiation therapy (XRT)/external beam irradiation including protons: >= 4 weeks(28 days) including palliative radiation therapy to the chest. >= 14 days afterve local XRT to areas other than the chest or for whole braindiotherapy
    • Radiopharmaceutical therapy (e.g., radiolabeled antibody, samarium): >= 42 daysystemically administered radiopharmaceutical therapy
    • Patients must not have received prior HER2 therapies including antibody drugjugates (e.g. TDM-1 or DS-8201a), HER2 directed cellular therapies, HER2herapy (e.g. trastuzumab, pertuzumab) or small molecule antagonists ofHER2 (e.g lapatinib or neratinib)
  • Patients must be at least 7 days from the date of last surgery
  • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3, (granulocytey-stimulating factor [G-CSF] administration is not allowed within 1 week prior to1 screening assessment) (for patients with solid tumors without known bone marrowvolvement)
  • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receivingusions for at least 7 days prior to enrollment) (for patients withd tumors without known bone marrow involvement)
  • Hemoglobin >= 8.0 g/dL at baseline (Red Blood Cell transfusion is not allowed within 1week prior to screening assessment) (for patients with solid tumors without known bonew involvement)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60L/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
    • Age: 12 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
    • Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
    • Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
      • For participants less than 18 years of age that screen fail only based on24 hour urine collection may be used instead to confirmgibility. A calculated GFR > 60 mL/min/1.73 m^2 using a 24 hourwill meet criteria for inclusion on this trial
  • Bilirubin (sum of conjugated + unconjugated or total) =< 1.5 x upper limit of normal
    (ULN) for age. For patients with documented Gilbert's syndrome (unconjugatedhyperbilirubinemia) bilirubin must be < 3 x ULN for age (patients with solid tumors)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) andum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3LN. (if liver metastases present =< 5 x ULN). For the purpose of this study, theLN for ALT is 45 U/L regardless of baseline and the ULN for AST is 50 U/L regardlessbaseline (patients with solid tumors)
  • Serum albumin >= 2.5 g/dL (patients with solid tumors)
  • International normalized ratio (INR)/prothrombin time (PT) and either partialhromboplastin or activated partial thromboplastin time (aPTT) =< 1.5 x ULN (patientswith solid tumors)
  • Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% byher an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 daysbefore Step 1 enrollment
  • Corrected QT interval (QTc) prolongation to < 470 ms (females) or < 450 ms (males)based on average triplicate 12-lead electrocardiogram (ECG)
  • Pulse oximetry > 93% on room air
  • Patients with seizure disorder may be enrolled if on anticonvulsants and welld as evidenced by no increase in seizure frequency in the prior 7 days
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE]version [v]5) resulting from prior chemotherapy, surgery, and/or radiation must be =<grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR isgible
  • All patients and/or their parents or legally authorized representatives must sign awritten informed consent. Assent, when appropriate, will be obtained according toutional guidelines
Exclusion Criteria:
  • Pregnant, planning to become pregnant, or breast-feeding women will not be entered onhis study because there is yet no available information regarding human fetal orgenic toxicities. Pregnancy tests must be obtained in girls who arehal. Males or females of reproductive potential may not participate unlesshey have agreed to use two effective methods of birth control, including a medicallyd barrier or contraceptive method (e.g., male or female condom) for theduration of the study and upon completion of the study and for at least 7 months ford 4 months for males after the last dose of study drug. Abstinence is anble method of birth control
    • Methods considered as highly effective methods of contraception include:
      • Combined (estrogen and progestogen containing) hormonal contraceptiond with inhibition of ovulation:
        • Oral
        • Intravaginal
        • Transdermal
      • Progestogen-only hormonal contraception associated with inhibition ofvulation
        • Oral
        • Injectable
        • Implantable
      • Intrauterine device (IUD)
      • Intrauterine hormone-releasing system (IUS)
      • Bilateral tubal occlusion
      • Vasectomized partner
      • Complete sexual abstinence defined as refraining from heterosexualurse. Periodic abstinence (calendar, symptothermal, post-ovulationhods) is not an acceptable method of contraception
  • Non-child-bearing potential defined as pre-menopausal females with a documented tubal
    ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneoushea (in questionable cases, a blood sample with simultaneousulating hormone [FSH] > 40 mIU/mL and estradiol < 40 pg/mL [< 147 pmol/L]y). Females on hormone replacement therapy (HRT) and whose menopausalus is in doubt will be required to use one of the contraception methods outlinedwomen of child-bearing potential if they wish to continue their HRT during theudy. Otherwise, they must discontinue HRT to allow confirmation of post-menopausalus prior to study enrollment. For most forms of HRT, at least 2-4 weeks willbetween the cessation of therapy and the blood draw; this interval depends onhe type and dosage of HRT. Following confirmation of their post-menopausal status,hey can resume use of HRT during the study without use of a contraceptive method
  • Male subjects must not freeze or donate sperm starting at Screening and throughout theudy period, and at least 4 months after the final study drug administration.Preservation of sperm should be considered prior to enrolment in this study
  • Female subjects must not donate, or retrieve for their own use, ova from the time ofg and throughout the study treatment period, and for at least 7 months afterhe final study drug administration
  • Patients receiving corticosteroids who have not been on a stable or decreasing dose ofd for at least 7 days prior to enrollment are not eligible. If used todify immune adverse events related to prior therapy, >= 14 days must have elapseddose of corticosteroid
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anti-cancer agents are not eligible
  • Patients who are receiving cyclosporine, tacrolimus or other agents to preventgraft-versus-host disease post bone marrow transplant are not eligible for this trial
  • Patients who are receiving chloroquine or hydroxychloroquine within 14 days are notgible for this trial
  • Patients who have received a prior solid organ transplantation are not eligible
  • Patients with a medical history of myocardial infarction within 180 days beforeymptomatic congestive heart failure (CHF) (New York Heart AssociationClass II to IV) or troponin levels consistent with myocardial infarction as definedding to the manufacturer 28 days prior to enrollment are not eligible
  • Patients who have a pleural effusion, ascites or pericardial effusion that requiresdrainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy(CART) are not eligible
  • Patients who have spinal cord compression or clinically active central nervous systemdefined as untreated and symptomatic, or requiring therapy withds or anticonvulsants to control associated symptoms are not eligible
  • Patients with a known history of severe hypersensitivity to DS-8201a or any excipientd in the DS-8201a drug formulation are not eligible
  • Patients who have an uncontrolled infection or non-healing surgical site are notgible
  • Patients with a known history of substance abuse or any other clinically significantdical conditions (i.e. psychological conditions) that may, in the opinion of thevestigator, interfere with the patient's participation in the clinical study orvaluation of the clinical study results are not eligible
  • Patients who have pulmonary compromise, ex hypoxia, resulting from intercurrentulmonary illnesses including, but not limited to, any underlying pulmonary disorder(i.e. pulmonary emboli within three months of the study enrollment, severe asthma,vere chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleuralusion etc.), or prior pneumonectomy are not eligible
  • Patients who have a history of (non-infectious) ILD (interstitial lungdisease)/pneumonitis that required steroids, has current ILD/pneumonitis, or whereuspected ILD/pneumonitis cannot be ruled out by imaging at screening are not eligible
  • Patients who have a pleural effusion, ascites or pericardial effusion that requiresdrainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy(CART) are not eligible. (Drainage and CART are not allowed within 2 weeks prior tog assessment)
  • Patients who, in the opinion of the investigator, may not be able to comply with they monitoring requirements of the study are not eligible

Updated on 14 Sep 2024. Study ID: NCI-2020-08428, PHO-COG-PEPN1924, 11339
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