Combination Chemotherapy and Pegfilgrastim in Treating Patients With Previously Untreated Germ Cell Tumors
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as cisplatin, ifosfamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy.
PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy together with pegfilgrastim works in treating patients with previously untreated germ cell tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
-
Determine the efficacy of chemotherapy comprising paclitaxel, ifosfamide, and cisplatin in combination with pegfilgrastim in patients with previously untreated intermediate- or poor-risk germ cell tumors.
-
Determine the safety of this regimen in these patients.
-
Determine the toxicity of this regimen in these patients.
OUTLINE: Patients receive paclitaxel IV over 120-180 minutes on days 1 and 2, cisplatin IV over 30 minutes and ifosfamide IV over 120 minutes on days 1-5, and pegfilgrastim subcutaneously on day 6. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Some patients may required surgery after chemotherapy and, if viable non-teratomatous germ cell tumor is found in the surgical specimen and there is no interval disease progression, these patients may receive 1-2 more courses of chemotherapy after surgery.
After completion of study treatment, patients are followed up at 28 days and then every 2 months for up to 1 year.
PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Paclitaxel, Ifosfamide, and Cisplatin -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. |
Biological: pegfilgrastim
Drug: cisplatin
Drug: ifosfamide
Drug: paclitaxel
|
Outcome Measures
Primary Outcome Measures
- Rate of Complete Response [3 years]
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions
Secondary Outcome Measures
- Progression-free Survival [Up to 8 years]
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Percentage of Participants With Progression Free Survival [3 years]
Progression Free Survival at 3 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Number of Patients With Treatment Related Toxicity [3 years]
Toxicity evaluated and graded according to the National Cancer Institute, Version 3.0
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically confirmed germ cell tumor meeting 1 of the following criteria:
-
Poor risk, defined by any of the following:
-
Testis or retroperitoneal primary site nonseminoma histology without visceral metastases but with "poor-risk" markers, defined by any of the following:
-
Pretreatment serum lactate dehydrogenase (LDH) > 10 times upper limit of normal (ULN)
-
Pretreatment serum human chorionic gonadotropin (HCG) > 50,000 IU/L
-
Pretreatment serum alpha fetoprotein (AFP) > 10,000 ng/mL
-
Testis or retroperitoneal primary site nonseminoma histology with one or more nonpulmonary visceral metastases, including any of the following (regardless of serum tumor marker values):
-
Bone metastases
-
Brain metastases
-
Hepatic metastases
-
Any nonpulmonary metastases (i.e., skin, spleen)
-
Mediastinal primary site nonseminoma histology regardless of serum tumor marker levels or presence/absence of visceral metastases
-
Modified intermediate risk, defined by any of the following:
-
Testis or retroperitoneal primary site nonseminoma histology with no nonpulmonary visceral metastases, and with any of the following serum marker values:
-
Pretreatment serum LDH 3.0-10 times ULN
-
Pretreatment serum HCG 5,000-50,000 IU/L
-
Pretreatment serum AFP 1,000-10,000 ng/mL
-
Seminoma histology with one or more nonpulmonary visceral metastases, including any of the following (regardless of serum tumor marker values or primary site):
-
Bone metastases
-
Brain metastases
-
Hepatic metastases
-
Any nonpulmonary visceral metastases (i.e., skin, spleen)
-
Previously untreated disease
-
Measurable or evaluable disease
PATIENT CHARACTERISTICS:
-
WBC ≥ 3,000/mm^3
-
Platelet count ≥ 100,000/mm^3
-
Creatinine normal or creatinine clearance > 50 mL/min (unless renal dysfunction is due to tumor obstructing the ureters)
-
AST and ALT ≤ 3 times ULN
-
Bilirubin ≤ 2.0 times ULN
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
No concurrent malignancy except for nonmelanoma skin cancer
-
No known HIV positivity
-
No active infections
PRIOR CONCURRENT THERAPY:
-
Recovered from prior surgery
-
More than 30 days since prior radiotherapy and recovered (unless evidence of progressive disease has been documented)
-
No prior chemotherapy
-
No other concurrent cytotoxic therapy
-
Concurrent radiotherapy and surgery allowed for treatment of brain metastases
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles | California | United States | 90089-9181 |
| 2 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Darren Feldman, MD, Memorial Sloan Kettering Cancer Center
- Principal Investigator: Robert J. Motzer, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 07-044
- MSKCC-07044
Study Results
Participant Flow
| Recruitment Details | Protocol Open to Accrual 03/27/2007 Protocol Closed to Accrual 8/13/2013 Primary Completion Date 06-13-2016 Recruitment Location is the medical clinic |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Paclitaxel, Ifosfamide, and Cisplatin |
|---|---|
| Arm/Group Description | -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. pegfilgrastim cisplatin ifosfamide paclitaxel |
| Period Title: Overall Study | |
| STARTED | 60 |
| COMPLETED | 56 |
| NOT COMPLETED | 4 |
Baseline Characteristics
| Arm/Group Title | Paclitaxel, Ifosfamide, and Cisplatin |
|---|---|
| Arm/Group Description | -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. pegfilgrastim cisplatin ifosfamide paclitaxel |
| Overall Participants | 60 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
28
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
1.7%
|
| Male |
59
98.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
12
20%
|
| Not Hispanic or Latino |
45
75%
|
| Unknown or Not Reported |
3
5%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
2
3.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
3.3%
|
| White |
51
85%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
5
8.3%
|
| Region of Enrollment (Count of Participants) | |
| United States |
60
100%
|
Outcome Measures
| Title | Rate of Complete Response |
|---|---|
| Description | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Paclitaxel, Ifosfamide, and Cisplatin |
|---|---|
| Arm/Group Description | -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. pegfilgrastim cisplatin ifosfamide paclitaxel |
| Measure Participants | 56 |
| Complete Response |
38
63.3%
|
| PR-Negative |
7
11.7%
|
| Incomplete Response |
11
18.3%
|
| Title | Progression-free Survival |
|---|---|
| Description | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Time Frame | Up to 8 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Paclitaxel, Ifosfamide, and Cisplatin |
|---|---|
| Arm/Group Description | -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. pegfilgrastim cisplatin ifosfamide paclitaxel |
| Measure Participants | 60 |
| Median (Full Range) [years] |
4.4
|
| Title | Percentage of Participants With Progression Free Survival |
|---|---|
| Description | Progression Free Survival at 3 years. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Paclitaxel, Ifosfamide, and Cisplatin |
|---|---|
| Arm/Group Description | -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. pegfilgrastim cisplatin ifosfamide paclitaxel |
| Measure Participants | 60 |
| Number (95% Confidence Interval) [percentage of patients] |
72
|
| Title | Number of Patients With Treatment Related Toxicity |
|---|---|
| Description | Toxicity evaluated and graded according to the National Cancer Institute, Version 3.0 |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Paclitaxel, Ifosfamide, and Cisplatin |
|---|---|
| Arm/Group Description | -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. pegfilgrastim cisplatin ifosfamide paclitaxel |
| Measure Participants | 60 |
| Count of Participants [Participants] |
60
100%
|
Adverse Events
| Time Frame | Day 1, 8 and 15 during each treatment cycle (1 cycle = 21 days). Follow up evaluation will be assessed after 28 days off study as often as every 4-8 weeks for the first year for patients who complete study or withdraw for reason other than progression of disease. For patients who come off study for disease progression, follow-up as often as every 8 weeks for the first year. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Paclitaxel, Ifosfamide, and Cisplatin | |
| Arm/Group Description | -Paclitaxel is administered first, 120 mg/m2 on days 1 and 2 every three weeks for four cycles. Cisplatin is administered at 20 mg/m2 over approximately 30 minutes daily for five days every three weeks for four courses. -The ifosfamide is given last with 1200 mg/m2 daily for five days every three weeks for four cycles. pegfilgrastim cisplatin ifosfamide paclitaxel | |
All Cause Mortality |
||
| Paclitaxel, Ifosfamide, and Cisplatin | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/60 (8.3%) | |
Serious Adverse Events |
||
| Paclitaxel, Ifosfamide, and Cisplatin | ||
| Affected / at Risk (%) | # Events | |
| Total | 34/60 (56.7%) | |
| Blood and lymphatic system disorders | ||
| Febrile Neutropenia | 9/60 (15%) | |
| Hemoglobin | 2/60 (3.3%) | |
| Cardiac disorders | ||
| Atrial tachycardia/Paroxysmal Atrial Tachycardia | 1/60 (1.7%) | |
| Cardiac General, other | 2/60 (3.3%) | |
| Gastrointestinal disorders | ||
| Constipation | 1/60 (1.7%) | |
| Diarrhea | 1/60 (1.7%) | |
| Hemorrhage, Duodenum | 1/60 (1.7%) | |
| Hemorrhage, Esophagus | 1/60 (1.7%) | |
| Nausea | 13/60 (21.7%) | |
| Pain - Abdomen NOS | 2/60 (3.3%) | |
| Vomiting | 13/60 (21.7%) | |
| General disorders | ||
| Fatigue | 2/60 (3.3%) | |
| Fever (in the absence of neutropenia) | 1/60 (1.7%) | |
| Pain - Chest/thorax NOS | 2/60 (3.3%) | |
| Pain - Throat/pharynx/larynx | 3/60 (5%) | |
| Immune system disorders | ||
| Allergy/Immunology, other | 3/60 (5%) | |
| Infections and infestations | ||
| Infection w/ Gr 3/4 Neut, Kidney | 1/60 (1.7%) | |
| Investigations | ||
| Creatinine | 3/60 (5%) | |
| Leukocytes | 6/60 (10%) | |
| Neutrophils/granulocytes | 10/60 (16.7%) | |
| Metabolism and nutrition disorders | ||
| Anorexia | 1/60 (1.7%) | |
| Dehydration | 3/60 (5%) | |
| Hypomagnesemia | 1/60 (1.7%) | |
| Platelets | 1/60 (1.7%) | |
| Hypokalemia | 1/60 (1.7%) | |
| Hyponatremia | 1/60 (1.7%) | |
| Musculoskeletal and connective tissue disorders | ||
| Pain - Back | 2/60 (3.3%) | |
| Nervous system disorders | ||
| Dizziness | 2/60 (3.3%) | |
| Encephalopathy | 1/60 (1.7%) | |
| Syncope | 1/60 (1.7%) | |
| Psychiatric disorders | ||
| Confusion | 1/60 (1.7%) | |
| Renal and urinary disorders | ||
| Cystitis | 1/60 (1.7%) | |
| Obstruction, GU - Ureter | 1/60 (1.7%) | |
| Renal failure | 1/60 (1.7%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/60 (1.7%) | |
| Dyspnea | 3/60 (5%) | |
| Vascular disorders | ||
| Chyle or lymph leakage | 1/60 (1.7%) | |
| Hematoma | 1/60 (1.7%) | |
| Hypotension | 5/60 (8.3%) | |
| Thrombosis/embolism | 4/60 (6.7%) | |
Other (Not Including Serious) Adverse Events |
||
| Paclitaxel, Ifosfamide, and Cisplatin | ||
| Affected / at Risk (%) | # Events | |
| Total | 60/60 (100%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin | 15/60 (25%) | |
| Febrile neutropenia | 4/60 (6.7%) | |
| Ear and labyrinth disorders | ||
| Tinnitus | 7/60 (11.7%) | |
| Gastrointestinal disorders | ||
| Nausea | 19/60 (31.7%) | |
| Vomiting | 9/60 (15%) | |
| Diarrhea | 6/60 (10%) | |
| Mucositis - oral cavity | 4/60 (6.7%) | |
| Constipation | 3/60 (5%) | |
| General disorders | ||
| Fatigue | 17/60 (28.3%) | |
| Investigations | ||
| Leukocytes | 13/60 (21.7%) | |
| Neutrophils/granulocytes | 13/60 (21.7%) | |
| Platelets | 13/60 (21.7%) | |
| ALT | 11/60 (18.3%) | |
| AST | 9/60 (15%) | |
| Alkaline phosphatase | 9/60 (15%) | |
| Lymphopenia | 7/60 (11.7%) | |
| Hyperbilirubinemia | 6/60 (10%) | |
| INR | 6/60 (10%) | |
| Amylase | 4/60 (6.7%) | |
| Metabolism and nutrition disorders | ||
| Hyponatremia | 11/60 (18.3%) | |
| Hyperglycemia | 10/60 (16.7%) | |
| Hypoalbuminemia | 9/60 (15%) | |
| Hypomagnesemia | 8/60 (13.3%) | |
| Hypokalemia | 5/60 (8.3%) | |
| Hypoglycemia | 4/60 (6.7%) | |
| Dehydration | 3/60 (5%) | |
| Hypophosphatemia | 3/60 (5%) | |
| Musculoskeletal and connective tissue disorders | ||
| Pain - Joint | 3/60 (5%) | |
| Nervous system disorders | ||
| Neuropathy: sensory | 11/60 (18.3%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnea | 6/60 (10%) | |
| Hiccups | 3/60 (5%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash: acne/acneiform | 8/60 (13.3%) | |
| Alopecia | 5/60 (8.3%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Darren Feldman, MD |
|---|---|
| Organization | Memorial Sloan Kettering Cancer Center |
| Phone | 646-422-4491 |
| feldmand@mskcc.org |
- 07-044
- MSKCC-07044