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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary: This partially randomized 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 Summary:

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- 50 years) with stage I (low risk) malignant germ cell tumors, and at least 98% 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.

III. 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).

IV. 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 and nephrotoxicity 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.

III. To assess the utility of using an established panel of four circulating micro ribonucleic acid (RNA)s as a universal marker of diagnosis, recurrence and
Sponsor: Children's Oncology Group

Current Primary Outcome:

  • EFS [ Time Frame: The time from study entry to the date of death, date of disease progression or recurrence, date of second malignant neoplasm or date of last contact and ascertained as alive, whichever comes first, assessed up to 5 years ]
  • Overall survival (OS) [ Time Frame: The time from randomization to date of date of death or date of last follow-up and ascertained as alive, assessed up to 8 years ]
    A 1-sided lower 85% confidence limit for the 2-year survival will be constructed, and if this confidence limit is greater than 0.95, it will be concluded that the strategy provides sufficient OS.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Content validity and understandability of AYA-Hearing Screen assessed by questionnaire [ Time Frame: Baseline ]
  • Incidence of ototoxicity [ Time Frame: 4 weeks after the last dose of platin therapy ]
    Will compare the proportion of patients who demonstrate hearing loss according to the International Society of Pediatric Oncology criteria.
  • Novel genetic variants associated with an increased risk of platinum-associated ototoxicity as determined by standard audiology [ Time Frame: Up to 10 years ]
    For each candidate gene, will perform an exact two-sided test for the equality of binomial proportions for the event - patient has the candidate gene. The two groups compared will be defined by the presence of SHL. Will use the Bonferroni correction to control experiment-wise error and designate the result as significant if the observed p-value is less than or equal to 0.0025.
  • Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ]
    Will use categorical data methods and estimate the probability of demonstrating an elevated miRNA value as the proportion of patients who have the particular miRNA elevated.
  • Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ]
    Will compare the diagnostic sensitivity of serum markers, particularly elevated alpha-fetoprotein, to that of elevated microRNA for each of the microRNAs, as well as the characteristic any microRNA elevated. Will perform McNemar's test. The result for each serum evaluation (elevated or not elevated) for each sample on which both serum marker and microRNA evaluation are obtained will be cross tabulated and the p-value associated with McNemar's test calculated. A p-value of 0.05 or less will be considered evidence of differential sensitivity.


Original Secondary Outcome: Same as current

Information By: Children's Oncology Group

Dates:
Date Received: February 14, 2017
Date Started: May 2017
Date Completion: December 2022
Last Updated: May 8, 2017
Last Verified: May 2017