A Phase 3 interventional study of conventional surgery and cisplatin in Childhood Embryonal Tumor, Childhood Extracranial Germ Cell Tumor and Childhood Extragonadal Germ Cell Tumor, sponsored by Children's Oncology Group. Completed at 126 sites in 6 countries. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2021-07-13.
Sponsored by Children's Oncology Group · Phase 3, Interventional, and Treatment
This phase III trial is studying surgery followed by combination chemotherapy to see how well it works in treating children with germ cell tumors that are not located in the head. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is effective in decreasing the recurrence of childhood germ cell tumors.
OBJECTIVES:
I. Determine whether children with newly diagnosed low- or intermediate-risk extracranial germ cell tumors (GCTs) can maintain a 3-year event-free survival of at least 92% (for intermediate-risk tumors only) and overall survival of at least 95% (both low-risk and intermediate-risk tumors) after treatment with surgery followed by compressed cisplatin, etoposide, and bleomycin (low-risk disease closed to accrual as of 01/20/10).
II. Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for whom chemotherapy can be eliminated.
III. Determine the percentage of intermediate-risk patients who require only 3 courses of therapy.
IV. Determine the acute toxic effects of compressed therapy in these patients. V. Determine the long-term sequelae in patients treated with this regimen. VI. Determine the number of hospital days and total drug doses required for patients treated with compressed therapy.
VII. Compare the number of protocol-directed treatment days used in CCG-8882 vs the number of treatment days used in this study.
VIII. Determine the cytogenetic and molecular genetic features in patients treated with this regimen.
OUTLINE: Patients are stratified according to disease risk (low vs intermediate).
SURGERY: Patients undergo surgical resection.
Low-risk disease: Patients with gonadal primaries and no evidence of disease after surgery undergo monitoring for disease progression. Patients who remain disease free receive no further treatment. Patients who have disease progression after surgery receive compressed induction chemotherapy. (closed to accrual as of 01/20/2010)
Intermediate-risk disease: After surgery, patients proceed to compressed induction chemotherapy.
COMPRESSED INDUCTION CHEMOTHERAPY: Patients receive cisplatin IV over 90 minutes and etoposide IV over 90 minutes on days 1-3 and bleomycin IV over ≥ 10 minutes on day 1. Treatment repeats every 3 weeks for 3 courses (weeks 0, 3, and 6).
After completion of compressed induction chemotherapy, patients who have no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or who have abnormal tumor markers proceed to second-look surgery and/or 3 more courses of compressed consolidation chemotherapy.
SECOND-LOOK SURGERY: Patients undergo surgical resection of residual tumor. After surgery, patients who are in pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy.
COMPRESSED CONSOLIDATION CHEMOTHERAPY: Patients receive cisplatin, etoposide, and bleomycin as in induction chemotherapy in weeks 10, 13, and 16.
Patients are followed up monthly for 6 months, every 3 months for 18 months, and then annually for up to 10 years.
30 studies on the registry are indexed under Ovarian Germ Cell Cancer; 2 are open to participants now.
This study's enrollment of 302 is above the median of 29 across 22 interventional studies indexed under Ovarian Germ Cell Cancer.
Browse Ovarian Germ Cell Cancer studies →Children's Oncology Group is the lead sponsor of 448 studies on the registry; 36 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Extracranial germ cell tumor that contains 1 of the following malignant histologies: NOTE: Mixed germ cell tumors that include mature/immature teratoma are eligible provided 1 of the 3 histologies listed above is also present in the tumor.
Low-risk disease (closed to accrual as of 01/20/10)
Intermediate-risk disease
No patients with any of the following diagnoses:
Alpha-fetoprotein and beta human chorionic gonadotropin tumor markers known
or radioisotope ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes \& etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 \& 6). After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy. After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy. Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, \& 16.
Procedure: conventional surgery · Drug: cisplatin · Drug: etoposide · Biological: bleomycin sulfate · Other: laboratory biomarker analysis
Patients who are enrolled with stage I gonadal tumors receive no further anticancer therapy until evidence of tumor recurrence or the diagnosis of a second malignant neoplasm. Observation only for recurrence or development of an SMN
Also known as: surgery, conventional
Given IV
Also known as: CACP, CDDP, CPDD, DDP
Given IV
Also known as: EPEG, VP-16, VP-16-213
Given IV
Also known as: Blenoxane, BLEO, BLM
Correlative studies
Event-Free Survival (EFS)
Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.
Time frame: 3 Years after enrollment
Overall Survival (OS)
Percentage probability of being alive at 3 years following enrollment.
Time frame: 3 Years after enrollment
Days Hospitalized for Patients Who Receive Chemotherapy
Calculated to quantify the treatment cost associated with this regimen.
Time frame: Up to 126 days after the start of chemotherapy
Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0
The number of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher at any time during protocol therapy
Time frame: Up to 126 days after the start of chemotherapy
| Milestone | Arm I | Arm 2 |
|---|---|---|
| Started | 190 | 112 |
| Completed | 169 | 102 |
| Not completed | 21 | 10 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Physician decision | 11 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Ineligible | 8 | 8 |
| Withdrew: Disease at new site | 1 | 0 |
Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.
| Percent probability | Arm 1 |
|---|---|
| Event-Free Survival (EFS) | 87.0 (81.0 to 92.0) |
Percentage probability of being alive at 3 years following enrollment.
| Percent Probability | Arm I | Arm 2 |
|---|---|---|
| Overall Survival (OS) | 97.0 (93.0 to 99.0) | 99.0 (92.8 to 99.9) |
Calculated to quantify the treatment cost associated with this regimen.
| Days in the hospital | Arm I |
|---|---|
| Days Hospitalized for Patients Who Receive Chemotherapy | 14.08 ± 10.27 |
The number of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher at any time during protocol therapy
| patients | Arm I |
|---|---|
| Abdominal pain | 3 |
| Acute kidney injury | 1 |
| Lymphocyte count decrease | 2 |
| Iincrease in alanine aminotransferase | 1 |
| Neutrophil count decrease | 58 |
| Anemia | 10 |
| Increase in aspartate aminotransferase | 1 |
| Catheter related infection | 1 |
| Constipation | 1 |
| Dehydration | 1 |
| Encephalopathy | 1 |
| Febrile neutropenia | 9 |
| Fever | 3 |
| Hyperglycemia | 1 |
| Hyperkalemia | 1 |
| Hypocalcemia | 2 |
| Hypokalemia | 1 |
| Hypomagnesemia | 1 |
| Hyponatremia | 1 |
| Hypophosphatemia | 6 |
| Small intestine obstruction | 1 |
| Nausea | 5 |
| Non-cardiac chest pain | 1 |
| Other gastrointestinal disorders | 1 |
| Other infection | 10 |
| Platelet count decrease | 7 |
| Syncope | 1 |
| Vomiting | 4 |
| White blood cell decrease | 17 |
| Wound infection | 1 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm 2 (Observation) | — | 0/104 (0%) | 0/104 (0%) |
| Arm I (Chemotherapy) | — | 0/182 (0%) | 78/182 (42.9%) |
| Event | Arm 2 (Observation) | Arm I (Chemotherapy) |
|---|---|---|
| Neutrophil count decreasedInvestigations | 0/104 | 58/182 |
| White blood cell decreasedInvestigations | 0/104 | 17/182 |
| AnemiaBlood and lymphatic system disorders | 0/104 | 10/182 |
| Infections and infestations - Other, specifyInfections and infestations | 0/104 | 10/182 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/104 | 9/182 |
| Platelet count decreasedInvestigations | 0/104 | 7/182 |
| HypophosphatemiaMetabolism and nutrition disorders | 0/104 | 6/182 |
| NauseaGastrointestinal disorders | 0/104 | 5/182 |
| VomitingGastrointestinal disorders | 0/104 | 4/182 |
| Abdominal painGastrointestinal disorders | 0/104 | 3/182 |
| Age, Continuous(years) | Arm I | Arm 2 | Total |
|---|---|---|---|
| Mean | 9.57 ± 5.65 | 5.41 ± 5.93 | 8.02 ± 6.09 |
| Sex: Female, Male(Participants) | Arm I | Arm 2 | Total |
|---|---|---|---|
| Female | 145 | 29 | 174 |
| Male | 45 | 83 | 128 |
| Race (NIH/OMB)(Participants) | Arm I | Arm 2 | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 1 | 2 |
| Asian | 14 | 10 | 24 |
| Native Hawaiian or Other Pacific Islander | 1 | 3 | 4 |
| Black or African American | 22 | 8 | 30 |
| White | 128 | 72 | 200 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 24 | 18 | 42 |
| Region of Enrollment(participants) | Arm I | Arm 2 | Total |
|---|---|---|---|
| New Zealand | 2 | 3 | 5 |
| Canada | 16 | 8 | 24 |
| United States | 170 | 91 | 261 |
| Australia | 1 | 8 | 9 |
| Switzerland | 0 | 2 | 2 |
| Guam | 1 | 0 | 1 |
Showing the first 100 of 126 sites across 6 countries. Choose a country and city above to see the rest.
Ran from Nov 2003 to primary completion in Oct 2013, 118 months.
Results were first posted in Dec 2017, 4 years 2 months after primary completion.
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This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Cisplatin · Etoposide · Bleomycin