Extragonadal Germ Cell TumorPhase 1/2NCT00002558
Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors
A Phase 1/2 study testing filgrastim, carboplatin and etoposide in people with Extragonadal Germ Cell Tumor and Ovarian Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, carboplatin, and etoposide work in different ways to stop the growth of tumor cells, either by killing them or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Extragonadal Germ Cell Tumor, Ovarian Cancer, Testicular Germ Cell Tumor
- What is being tested?
- filgrastim, carboplatin and etoposide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1994to Apr 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male/Female with histologically confirmed GCT with review by the Department of Pathology at this center.
- Patients with advanced GCT, including patients with:
- measurable or evaluable disease,
- patients with only elevated serum tumor markers (AFP and/or HCG), or
- patients with known residual disease after postchemotherapy surgery. Eligible patients must have established clinical resistance to cisplatin by their failure to achieve a durable CR to a cisplatin-based regimen.
- Prior treatment limited to ≤ 6 prior cycles (≤ four cycles preferred) of cisplatin. (GROUP A)
Show all 19Show fewer
- Prior therapy > 6 cycles of cisplatin. (GROUP B)
- Therapy must have been discontinued at least 3 weeks before entry onto protocol.
- Patients must have one or more unfavorable prognostic factors for achieving a CR to cisplatin-based salvage therapy. These are:
- Extragonadal primary site.
- Testis/ovarian primary site with the best response of an IR to first-line therapy, or a partial response with normal tumor markers of six months or less in duration.
- Prior treatment with ifosfamide-containing therapy
- General medical condition sufficient to allow for general anesthesia at the time of pheresis catheter placement.
- Patients must have negative serology for Human Immunodeficiency Virus.
- Laboratory criteria for protocol entry:
- WBC ≥ 3000/ul Platelets 3 100,000/ul Cr Clearance > 50 cc/min
- (unless renal dysfunction is due to tumor obstructing the ureters in which case eligibility will be determined by the Principal Investigator).
- Age ≥ 15 years.
- Signed informed consent.
Who cannot join
- Presence of active infection
- Concurrent treatment with chemotherapy or
- Inability to comply with the treatment protocol or to undergo the specified follow-up tests for safety or effectiveness.
- Prior high-dose therapy with AuBMT.
- Patients must have recovered from recent surgery.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: PHASE I/II TRIAL OF SEQUENTIAL TAXOL/IFOSFAMIDE AND DOSEINTENSIVE CARBOPLATIN/ETOPOSIDE WITH STEM CELL SUPPORT IN CISPLATIN-RESISTANT GERM CELL TUMOR PATIENTS WITH UNFAVORABLE PROGNOSTIC FEATURES
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, carboplatin, and etoposide work in different ways to stop the growth of tumor cells, either by killing them or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed.
The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support.
PURPOSE: The purpose of this study is to determine the effects of an intensive sequence of chemotherapy drugs in patients with metastatic germ cell cancer. All of these chemotherapy drugs are known to be active in this disease.
Read the detailed description
OBJECTIVES:
- Determine the safety of paclitaxel and ifosfamide followed by carboplatin and etoposide with stem cell support in patients with unfavorable germ cell tumors with unfavorable prognostic factors and resistance to cisplatin.
- Determine the efficacy of this regimen as salvage therapy in these patients.
- Escalate the dose of carboplatin based on a target area under the concentration time curve and renal function, and determine the pharmacokinetics of carboplatin in selected patients.
- Determine the qualitative effects of paclitaxel and ifosfamide on hematopoietic progenitors in these patients.
OUTLINE: This is a dose escalation study of carboplatin.
- Part A: Patients receive paclitaxel IV continuously on day 1 and ifosfamide IV over 4 hours on days 2-4. Autologous peripheral blood stem cells (PBSC) are harvested on days 11-13. Filgrastim (G-CSF) is administered subcutaneously (SC) twice daily beginning 6 hours after completion of paclitaxel and ifosfamide infusions and continuing until the last day of leukapheresis. Treatment continues every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Before beginning the first course of chemotherapy, autologous bone marrow (ABM) is harvested, if possible, in case insufficient peripheral blood stem cells (PBSC) are harvested. Patients who were unable to undergo harvest of ABM before the first course of chemotherapy undergo harvest of ABM before beginning the second course of chemotherapy.
- Part B : Beginning 2 weeks after completion of regimen A, patients receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. PBSC are reinfused on day 5. G-CSF is administered SC twice daily beginning 6 hours after completion of etoposide and carboplatin infusions and continuing until blood counts recover. G-CSF is held on the morning of PBSC transplantation and restarted beginning 6 hours after completion of PBSC transplantation. Treatment continues every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with insufficient PBSC for the second course receive PBSC combined with ABM. Patients with insufficient PBSC for the third course receive ABM.
During the second part, cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.
After completion of parts A and B, some patients may undergo resection of residual masses.
- Being tested
- filgrastim, carboplatin, etoposide, ifosfamide, paclitaxel
- Keywords
- recurrent malignant testicular germ cell tumor, recurrent ovarian germ cell tumor, extragonadal germ cell tumor
- Medical subject headings
- Ovarian Neoplasms, Testicular Germ Cell Tumor, Testicular Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
carboplatinDrug
etoposideDrug
ifosfamideDrug
paclitaxelDrug
peripheral blood stem cell transplantationProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| chemotherapy administered with G-CSF and PBSC support | Experimental | The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support. Receives: Biological: filgrastim; Drug: carboplatin; Drug: etoposide; Drug: ifosfamide; Drug: paclitaxel; Procedure: peripheral blood stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Objective Response
Overall Objective Response will be assessed prior to dose-intensive therapy and at the completion of therapy. Complete disappearance of all clinical, radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). Patients must be free of disease for a minimum of 4 weeks. Partial Response: Complete disappearance of all biochemical evidence of disease in patients without a surgical procedure for a residual radiographic mass. Patients must demonstrate no biochemical recurrence or progression of radiographic masses for a minimum of four weeks (PR to chemotherapy}
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startJan 1994
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Extragonadal Germ Cell TumorStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Gnanamba V. Kondagunta, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00002558
- Sponsor's protocol ID
- 93-162
- Other IDs
- P30CA008748, MSKCC-93162, NCI-V94-0407
- Status last verified
- Apr 2016
- First submitted
- 1 Nov 1999
- Last updated
- 23 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Feldman DR, Sheinfeld J, Bajorin DF, Fischer P, Turkula S, Ishill N, Patil S, Bains M, Reich LM, Bosl GJ, Motzer RJ. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010 Apr 1;28(10):1706-13. doi: 10.1200/JCO.2009.25.1561. Epub 2010 Mar 1.
PubMed 20194867Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. doi: 10.1200/JCO.2006.06.9401.
PubMed 17194908
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PHASE I/II TRIAL OF SEQUENTIAL TAXOL/IFOSFAMIDE AND DOSEINTENSIVE CARBOPLATIN/ETOPOSIDE WITH STEM CELL SUPPORT IN CISPLATIN-RESISTANT GERM CELL TUMOR PATIENTS WITH UNFAVORABLE PROGNOSTIC FEATURES
- ClinicalTrials.gov ID
- NCT00002558
- Acronym / sponsor ID
- 93-162
- Keywords
- recurrent malignant testicular germ cell tumor, recurrent ovarian germ cell tumor, extragonadal germ cell tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 1994
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 23 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, carboplatin, and etoposide work in different ways to stop the growth of tumor cells, either by killing them or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed.
The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support.
PURPOSE: The purpose of this study is to determine the effects of an intensive sequence of chemotherapy drugs in patients with metastatic germ cell cancer. All of these chemotherapy drugs are known to be active in this disease.
Detailed description
OBJECTIVES:
- Determine the safety of paclitaxel and ifosfamide followed by carboplatin and etoposide with stem cell support in patients with unfavorable germ cell tumors with unfavorable prognostic factors and resistance to cisplatin.
- Determine the efficacy of this regimen as salvage therapy in these patients.
- Escalate the dose of carboplatin based on a target area under the concentration time curve and renal function, and determine the pharmacokinetics of carboplatin in selected patients.
- Determine the qualitative effects of paclitaxel and ifosfamide on hematopoietic progenitors in these patients.
OUTLINE: This is a dose escalation study of carboplatin.
- Part A: Patients receive paclitaxel IV continuously on day 1 and ifosfamide IV over 4 hours on days 2-4. Autologous peripheral blood stem cells (PBSC) are harvested on days 11-13. Filgrastim (G-CSF) is administered subcutaneously (SC) twice daily beginning 6 hours after completion of paclitaxel and ifosfamide infusions and continuing until the last day of leukapheresis. Treatment continues every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Before beginning the first course of chemotherapy, autologous bone marrow (ABM) is harvested, if possible, in case insufficient peripheral blood stem cells (PBSC) are harvested. Patients who were unable to undergo harvest of ABM before the first course of chemotherapy undergo harvest of ABM before beginning the second course of chemotherapy.
- Part B : Beginning 2 weeks after completion of regimen A, patients receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. PBSC are reinfused on day 5. G-CSF is administered SC twice daily beginning 6 hours after completion of etoposide and carboplatin infusions and continuing until blood counts recover. G-CSF is held on the morning of PBSC transplantation and restarted beginning 6 hours after completion of PBSC transplantation. Treatment continues every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with insufficient PBSC for the second course receive PBSC combined with ABM. Patients with insufficient PBSC for the third course receive ABM.
During the second part, cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.
After completion of parts A and B, some patients may undergo resection of residual masses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| chemotherapy administered with G-CSF and PBSC support | Experimental | Biological: filgrastim, Drug: carboplatin, Drug: etoposide, Drug: ifosfamide, Drug: paclitaxel, Procedure: peripheral blood stem cell transplantationThe design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Male/Female with histologically confirmed GCT with review by the Department of Pathology at this center.
- Patients with advanced GCT, including patients with:
- measurable or evaluable disease,
- patients with only elevated serum tumor markers (AFP and/or HCG), or
- patients with known residual disease after postchemotherapy surgery. Eligible patients must have established clinical resistance to cisplatin by their failure to achieve a durable CR to a cisplatin-based regimen.
Key exclusion criteria (5 listed)
- Presence of active infection
- Concurrent treatment with chemotherapy or
- Inability to comply with the treatment protocol or to undergo the specified follow-up tests for safety or effectiveness.
- Prior high-dose therapy with AuBMT.
- Patients must have recovered from recent surgery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastim | Biological | chemotherapy administered with G-CSF and PBSC support |
| carboplatin | Drug | chemotherapy administered with G-CSF and PBSC support |
| etoposide | Drug | chemotherapy administered with G-CSF and PBSC support |
| ifosfamide | Drug | chemotherapy administered with G-CSF and PBSC support |
| paclitaxel | Drug | chemotherapy administered with G-CSF and PBSC support |
| peripheral blood stem cell transplantation | Procedure or surgery | chemotherapy administered with G-CSF and PBSC support |
Primary outcome
Overall Objective Response
Time frame: 2 years
Overall Objective Response will be assessed prior to dose-intensive therapy and at the completion of therapy. Complete disappearance of all clinical, radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). Patients must be free of disease for a minimum of 4 weeks. Partial Response: Complete disappearance of all biochemical evidence of disease in patients without a surgical procedure for a residual radiographic mass. Patients must demonstrate no biochemical recurrence or progression of radiographic masses for a minimum of four weeks (PR to chemotherapy}
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20194867Feldman DR, Sheinfeld J, Bajorin DF, Fischer P, Turkula S, Ishill N, Patil S, Bains M, Reich LM, Bosl GJ, Motzer RJ. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010 Apr 1;28(10):1706-13. doi: 10.1200/JCO.2009.25.1561. Epub 2010 Mar 1.
- Results publication: PubMed 17194908Kondagunta GV, Bacik J, Sheinfeld J, Bajorin D, Bains M, Reich L, Deluca J, Budnick A, Ishill N, Mazumdar M, Bosl GJ, Motzer RJ. Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors. J Clin Oncol. 2007 Jan 1;25(1):85-90. doi: 10.1200/JCO.2006.06.9401.
Related trials for Extragonadal Germ Cell Tumor
RecruitingPhase 3
Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma
Active, not recruitingPhase 3
Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors
Germ Cell Tumor, Teratoma
RecruitingPhase 2
High-dose Chemotherapy as Second-line Drug Therapy for Relapsed Germ Cell Tumors
Germ Cell Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gnanamba V. Kondagunta, MD study chair
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing filgrastim, carboplatin and etoposide in people with Extragonadal Germ Cell Tumor and Ovarian Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Objective Response (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00002558, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2016.