IRB Study Number 17-1075
Status Recruiting
Phase Phase 3
Institutes Taussig Cancer Institute, Pediatric Institute
Description
Primary Aims
1 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.
2 To compare the event-free survival of a carboplatin vs. cisplatin-based regimen in the treatment of pediatric, adolescent and young adult patients with standard risk germ cell tumors.
3 To compare the EFS of a carboplatin-based regimen (CEb) vs. a cisplatin-based regimen (PEb) in children (less than 11 years in age) with standard risk GCT.
4 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 Aims
1 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.
2 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 Aims
1 To prospectively determine the correlation of tumor marker decline (α-FP and β-HCG) with clinical outcome in low and standard risk germ cell tumor patients.
2 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.
3 Assess the relationship between hearing loss as measured by audiometry with the effects of tinnitus as assessed on the AYA-HEARS instrument.
Inclusion Criteria
3.2.1.1 Low Risk Stratum (Stage I Ovarian Immature Teratoma and Stage I Malignant GCT (all sites))
Patients must be < 50 years of age at enrollment.
3.2.1.2 Standard Risk 1
Patients must be < 11 years of age at enrollment.
3.2.1.3 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 in the table below. Elevation of serum tumor markers without histologic confirmation is not sufficient for entry on the trial.
For COG, FIGO, AJCC and IGCCC staging criteria see Appendix II, Appendix III, Appendix IV and Appendix V, respectively.
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 ECOG scores of 0, 1, 2 or 3. Use Karnofsky for patients > 16 years of age and Lansky for patients 16 years of age (see Appendix VI).
Organ Function Requirements
Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients).
3.2.4.1 Adequate renal function defined as:
Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or
A serum creatinine based on age/gender as follows: (See protocol)
3.2.4.2 Adequate liver function defined as:
Total bilirubin 1.5 x upper limit of normal (ULN) for age, and
SGOT (AST) or SGPT (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).
3.2.4.3 Adequate pulmonary function defined as:
- No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
Pulmonary Function Tests (PFTs) are not required.
Exclusion Criteria
3.2.5.1 Patients with any diagnoses not listed in the table in Section 3.2.2 including: Pure dysgerminoma and pure seminoma, Pure mature teratoma, 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 (see Appendix V)], or Primary CNS germ cell tumor.
3.2.5.3 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.]
3.2.5.4 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.
3.2.5.5 Pregnancy and Breast Feeding
These criteria apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients).
3.2.5.5.1 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.
3.2.5.5.2 Lactating females who plan to breastfeed their infants.
3.2.5.5.3 Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
≥ 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:
o Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
o Dana Farber/ Harvard Cancer Center
o Hospital for Sick Children
o Children’s Hospital of Eastern Ontario
o Oregon Health and Science University
o Seattle Children’s Hospital
o Yale University
