Clinical Trials /

Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors

NCT03067181

Description:

This phase III trial studies how well active surveillance, bleomycin, carboplatin, etoposide, or cisplatin work in treating pediatric and adult patients with germ cell tumors. Active surveillance may help doctors to monitor subjects with low risk germ cell tumors after their tumor is removed. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Immature Ovarian Teratoma
  • Malignant Germ Cell Tumor
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
  • Official Title: A Phase 3 Study of Active Surveillance for Low Risk and a Randomized Trial of Carboplatin vs. Cisplatin for Standard Risk Pediatric and Adult Patients With Germ Cell Tumors

Clinical Trial IDs

  • ORG STUDY ID: AGCT1531
  • SECONDARY ID: NCI-2017-00178
  • SECONDARY ID: AGCT1531
  • SECONDARY ID: AGCT1531
  • SECONDARY ID: AGCT1531
  • SECONDARY ID: U10CA180886
  • NCT ID: NCT03067181

Conditions

  • Childhood Extracranial Germ Cell Tumor
  • Extragonadal Embryonal Carcinoma
  • Germ Cell Tumor
  • Malignant Germ Cell Tumor
  • Malignant Ovarian Teratoma
  • Stage I Ovarian Choriocarcinoma
  • Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage I Ovarian Teratoma AJCC v6 and v7
  • Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Stage I Testicular Choriocarcinoma AJCC v6 and v7
  • Stage I Testicular Embryonal Carcinoma AJCC v6 and v7
  • Stage I Testicular Yolk Sac Tumor AJCC v6 and v7
  • Stage II Ovarian Choriocarcinoma
  • Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Stage II Testicular Choriocarcinoma AJCC v6 and v7
  • Stage II Testicular Embryonal Carcinoma AJCC v6 and v7
  • Stage II Testicular Yolk Sac Tumor AJCC v6 and v7
  • Stage III Ovarian Choriocarcinoma
  • Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Stage III Testicular Choriocarcinoma AJCC v6 and v7
  • Stage III Testicular Embryonal Carcinoma AJCC v6 and v7
  • Stage III Testicular Yolk Sac Tumor AJCC v6 and v7
  • Stage IV Ovarian Choriocarcinoma
  • Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Testicular Mixed Choriocarcinoma and Embryonal Carcinoma
  • Testicular Mixed Choriocarcinoma and Teratoma
  • Testicular Mixed Choriocarcinoma and Yolk Sac Tumor

Interventions

DrugSynonymsArms
BleomycinBLEO, BLMArm I (bleomycin, carboplatin, etoposide)
Bleomycin SulfateBlanoxan, BleMomycine, Blenoxane, Bleo-cell, Bleo-S, Bleocin, Bleolem, Bleomycin Sulfas, Bleomycin Sulphate, Bleomycini Sulfas, Blexane, Oil BleoArm I (bleomycin, carboplatin, etoposide)
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboArm I (bleomycin, carboplatin, etoposide)
CisplatinAbiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, PlatosinArm II (bleomycin, etoposide, cisplatin)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16Arm I (bleomycin, carboplatin, etoposide)
Etoposide PhosphateEtopophosArm I (bleomycin, carboplatin, etoposide)

Purpose

This phase III trial studies how well active surveillance, bleomycin, carboplatin, etoposide, or cisplatin work in treating pediatric and adult patients with germ cell tumors. Active surveillance may help doctors to monitor subjects with low risk germ cell tumors after their tumor is removed. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate whether a strategy of complete surgical resection followed by surveillance can
      maintain an overall survival rate of at least 95.7% at two years for pediatric, adolescent
      and adult patients (ages 0 to < 50 years) with stage I (low risk) malignant germ cell tumors,
      and at least 95% for patients with ovarian pure immature teratoma.

      II. To compare the event-free survival of a carboplatin versus (vs.) cisplatin-based regimen
      in the treatment of pediatric, adolescent and young adult patients with standard risk germ
      cell tumors.

      IIa. To compare the event free survival (EFS) of a carboplatin-based regimen (carboplatin [C]
      etoposide [E] bleomycin [b]) vs. a cisplatin-based regimen (cisplatin [P]Eb) in children
      (less than 11 years in age) with standard risk germ cell tumors (GCT).

      IIb. To compare the EFS of a carboplatin-based regimen (BEC) vs. a cisplatin-based regimen
      (BEP) in adolescents and young adults (ages 11 - < 25 years) with standard risk GCT.

      SECONDARY OBJECTIVES:

      I. To compare the incidence of ototoxicity in children, adolescents and young adults with
      standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to
      cisplatin-based chemotherapy.

      II. To refine and validate a novel patient-reported measure of hearing outcomes for children,
      adolescents and young adults with standard risk germ cell tumors.

      EXPLORATORY OBJECTIVES:

      I. To prospectively determine the correlation of tumor marker decline (alpha-fetoprotein [FP]
      and beta-human chorionic gonadotropin [HCG]) with clinical outcome in low and standard risk
      germ cell tumor patients.

      II. To compare self-reported peripheral neuropathy and other patient-reported outcomes
      between children, adolescents and young adults with standard risk germ cell tumors treated
      with carboplatin-based chemotherapy as compared to cisplatin based chemotherapy.

      III. Assess the relationship between hearing loss as measured by audiometry with the effects
      of tinnitus as assessed on the Adolescent and Young Adult Hearing Screening (AYA-HEARS)
      instrument.

      OUTLINE:

      Patients with low-risk stage I grade 2, 3 ovarian immature teratoma or stage I malignant germ
      cell tumors undergo observation and can transfer to standard risk arm when eligibility
      criteria are met.

      Patients with standard risk 1 are randomized into 1 of 2 arms.

      ARM I (CEb): Patients receive bleomycin intravenously (IV) over 10 minutes and carboplatin IV
      over 1 hour on day 1. Patients also receive etoposide IV over 1-2 hours on days 1-5.
      Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or
      unacceptable toxicity.

      ARM II (PEb): Patients receive bleomycin IV over 10 minutes on day 1. Patients also receive
      etoposide IV over 1-2 hours and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats
      every 21 days for up to 4 cycles in the absence of disease progression or unacceptable
      toxicity.

      Patients with standard risk 2 are randomized into 1 of 2 arms.

      ARM III (BEC): Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide
      IV over 1-2 hours on days 1-5, and carboplatin IV over 1 hour on day 1. Treatment repeats
      every 21 days for up to 3 cycles in the absence of disease progression or unacceptable
      toxicity.

      ARM IV (BEP): Patients receive bleomycin IV over 10 minutes on days 1, 8, 15, etoposide IV
      over 1-2 hours on days 1-5, and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats
      every 21 days for up to 3 cycles in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up monthly to 12 months, every 2
      months to 24 months, every 6 months for years 3-5, and then annually for up to 10 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (bleomycin, carboplatin, etoposide)ExperimentalPatients receive bleomycin IV over 10 minutes and carboplatin IV over 1 hour on day 1. Patients also receive etoposide IV over 1-2 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  • Bleomycin
  • Bleomycin Sulfate
  • Carboplatin
  • Etoposide
  • Etoposide Phosphate
Arm II (bleomycin, etoposide, cisplatin)ExperimentalPatients receive bleomycin IV over 10 minutes on day 1. Patients also receive etoposide IV over 1-2 hours and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
  • Bleomycin
  • Bleomycin Sulfate
  • Cisplatin
  • Etoposide
  • Etoposide Phosphate
Arm III (bleomycin, etoposide, carboplatin)ExperimentalPatients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
  • Bleomycin
  • Bleomycin Sulfate
  • Carboplatin
  • Etoposide
  • Etoposide Phosphate
Arm IV (bleomycin, etoposide, cisplatin)ExperimentalPatients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
  • Bleomycin
  • Bleomycin Sulfate
  • Cisplatin
  • Etoposide
  • Etoposide Phosphate
Low-Risk (observation)ExperimentalPatients with stage I grade 2, 3 ovarian immature teratoma or low-risk stage I malignant germ cell tumors undergo observation and can transfer to standard risk arm when eligibility criteria are met.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Low risk stratum (stage I ovarian immature teratoma and stage I malignant GCT [all
                 sites]): Patients must be < 50 years of age at enrollment
    
              -  Standard risk 1: Patient must be < 11 years of age at enrollment
    
              -  Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
    
              -  Newly diagnosed patients must have histologic verification of a primary extracranial
                 germ cell tumor in any of the categories outlined; elevation of serum tumor markers
                 without histologic confirmation is not sufficient for entry on the trial
    
                   -  NOTE: for low risk patients, materials for rapid surgical central review must be
                      sent within 72 hours of study enrollment
    
              -  Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology
                 Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB;
                 grade: 2 or 3; histology: pure immature teratoma (may contain =< 5% of microscopic
                 yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of
                 mediastinal germ cell tumor [MGCT]); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG
                 institutional normal; age (years) < 50
    
              -  Low risk stage I MCGT; site: ovarian, testicular, or extragonadal; stage: COG stage I,
                 FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA,
                 IB and IS; histology: must contain at least one of the following: yolk sac tumor,
                 embryonal carcinoma, or choriocarcinoma (pure or mixed); age (years) < 50
    
              -  Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage
                 II-IV, FIGO stage IC, FIGO stage II-IV; histology: must contain at least one of the
                 following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed);
                 age (years) < 11
    
              -  Standard risk 2 (SR2)
    
                   -  Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology:
                      must contain at least one of the following: yolk sac tumor, embryonal carcinoma,
                      or choriocarcinoma (pure or mixed); age (years) >= 11 and < 25
    
                   -  Site: testicular; stage: COG stage II-IV, AJCC stage II, III, International Germ
                      Cell Consensus Classification (IGCCC) good risk; histology: must contain at least
                      one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma
                      (pure or mixed); tumor markers: must be IGCCC good risk; post op: alpha-FP <
                      1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 3.0 x
                      normal; age (years) >= 11 and < 25
    
                   -  Site: extragonadal; stage: COG stage II; histology: must contain at least one of
                      the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or
                      mixed) age (years) >= 11 and < 25
    
              -  Notes:
    
                   -  IGCCC criteria only apply to SR2 patients with a testicular primary tumor
    
                   -  Use post-op tumor marker levels to determine IGCCC risk group
    
                   -  For the low risk stage I MGCT and the standard risk arms, components of yolk sac
                      tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of
                      GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the
                      only malignant component present, then it must be deemed by the pathologist to be
                      greater than a "microscopic component" of yolk sac tumor (i.e. > 5%)
    
              -  Patients must have a performance status corresponding to Eastern Cooperative Oncology
                 Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and
                 Lansky for patients =< 16 years of age
    
              -  Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1
                 and SR2 patients)
    
              -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
                 mL/min/1.73 m^2
    
              -  A serum creatinine based on age/gender as follows: (mg/dL)
    
                   -  1 month to < 6 months male: 0.4 female: 0.4
    
                   -  6 months to < 1 year male: 0.5 female: 0.5
    
                   -  1 to < 2 years male: 0.6 female: 0.6
    
                   -  2 to < 6 years male: 0.8 female: 0.8
    
                   -  6 to < 10 years male: 1 female: 1
    
                   -  10 to < 13 years male: 1.2 female: 1.2
    
                   -  13 to < 16 years: male: 1.5 female: 1.4
    
                   -  >= 16 years male: 1.7 female: 1.4
    
              -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
    
              -  Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
                 serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
                 upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT
                 is 45 U/L)
    
              -  No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if
                 there is clinical indication or determination; pulmonary function tests (PFTs) are not
                 required
    
              -  Eligibility criteria to participate in the pilot study of the AYA-Hears instrument
                 (patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will
                 not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be
                 enrolled on the AGCT1531 SR2 arm in order to participate
    
              -  >= 11 and < 25 years old at enrollment
    
              -  Able to fluently speak and read English
    
              -  Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy
                 including diagnoses other than germ cell tumor
    
              -  Followed for cancer or survivorship care at one of the following institutions:
    
                   -  Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    
                   -  Dana Farber/Harvard Cancer Center
    
                   -  Hospital for Sick Children
    
                   -  Children's Hospital of Eastern Ontario
    
                   -  Oregon Health and Science University
    
                   -  Seattle Children's Hospital
    
                   -  Yale University
    
            Exclusion Criteria:
    
              -  Patients with any diagnoses not listed including:
    
                   -  Stage I testicular cancer patients who have undergone primary RPLND
                      (retroperitoneal lymph node dissection)
    
                   -  Pure dysgerminoma and pure seminoma
    
                   -  Pure mature teratoma
    
                   -  Pure immature teratoma COG stage I, grade I
    
                   -  Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >=
                      1000 ng/mL
    
                   -  Pure immature teratoma COG stage II - IV or FIGO stage IC to IV
    
                   -  "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or
                      IV EG, or IGCCC intermediate or poor risk testicular), or
    
                   -  Primary central nervous system (CNS) germ cell tumor
    
              -  Patients must have had no prior systemic therapy for the current cancer diagnosis
    
              -  Patients must have had no prior radiation therapy with the exception of CNS
                 irradiation of brain metastases; (this exception only applies to SR1 patients; any
                 patients over age 11 with distant metastases to brain [stage IV disease] would be
                 considered poor risk and therefore not eligible for this trial)
    
              -  Patients with significant respiratory compromise due to either abdominal tumor
                 limiting diaphragmatic excursion or pulmonary metastases should not receive bleomycin
                 and are ineligible for the trial
    
              -  Female patients who are pregnant since fetal toxicities and teratogenic effects have
                 been noted for several of the study drugs; a pregnancy test is required for female
                 patients of childbearing potential; (this criteria applies ONLY to patients who will
                 receive chemotherapy [SR1 and SR2 patients])
    
              -  Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to
                 patients who will receive chemotherapy [SR1 and SR2 patients])
    
              -  Sexually active patients of reproductive potential who have not agreed to use an
                 effective contraceptive method for the duration of their study participation; (this
                 criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2
                 patients])
          
    Maximum Eligible Age:49 Years
    Minimum Eligible Age:N/A
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall survival
    Time Frame:Two years post enrollment
    Safety Issue:
    Description:The time from study entry to the date of death, or date of last contact and ascertained as alive, whichever comes first.

    Secondary Outcome Measures

    Measure:Percentage of participants with hearing loss
    Time Frame:4 weeks after the last dose of platin therapy
    Safety Issue:
    Description:The hearing loss is evaluated according to the International Society of Pediatric Oncology criteria.
    Measure:Number of participants by understanding score category in the Adolescents and Young Adults-Hearing Screen
    Time Frame:Baseline
    Safety Issue:
    Description:Understanding score will be rated on a 5-point Likert scale ranging from 0 = completely incorrect to 4 = completely correct.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Children's Oncology Group

    Last Updated

    November 14, 2019