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High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors

Primary Purpose

Testicular Cancer

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Gemcitabine

Docetaxel

Melphalan

Carboplatin

Mesna

Ifosfamide

Etoposide

Stem Cell Transplant

About this trial

This is an interventional treatment trial for Testicular Cancer focused on measuring Testis, Relapsed Testicular Cancer, Bevacizumab, Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF, Carboplatin, Paraplatin, Docetaxel, Taxotere, Etoposide, VePesid, Gemcitabine, Gemcitabine Hydrochloride, Gemzar, Ifosfamide, Ifex, Melphalan, Alkeran

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female patients, age 12 to 65 years.
Patients with seminomatous or nonseminomatous germ-cell tumors (GCT) in one of the following groups: A) First relapse or progression or second response with an intermediate or high risk according to the Beyer model. B) Second relapse or beyond.
Adequate renal glomerular and tubular function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL, and urinary protein excretion </=500 mg/day.
Adequate hepatic function, as defined by ALT and AST </=3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase </=2 x ULN or considered not clinically significant.
Adequate pulmonary function with FEV1 (Forced expiratory volume in the first second), FVC (Forced vital capacity) and DLCO (diffusing capacity of the lung for carbon monoxide) >/=50% of predicted, corrected for volume and hemoglobin.
Adequate cardiac function with LVEF (left ventricular ejection fraction) >/=40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
Zubrod performance status 0-2.
A minimum apheresis collection of 5 million CD34+ cells/kg of autologous hematopoietic progenitor cells (AHPC).
Written informed consent by patients and/ or their parents or legal guardians. Assent for those patients inclusive of ages 12 to 17.

Exclusion Criteria:

Growing teratoma syndrome, defined as enlarging tumor masses with normal serum markers during chemotherapy for nonseminomatous GCT.
Major surgery within 30 days before the initiation of study treatment
Radiotherapy within 21 days prior to initiation of study treatment
Prior whole brain irradiation.
Patients with active central nervous system (CNS) disease, defined as brain or meningeal metastases that are not in complete remission.
Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/=10,000 copies/mL, or >/= 2,000 IU/mL).
Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients who either show chronic hepatitis C or positive hepatitis C serology.
Active infection requiring parenteral antibiotics.
HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts
Patients who have had a previous autologous or allogeneic stem cell transplant in the previous 12 months.
Positive pregnancy test in a female patient of childbearing potential defined as not post menopausal for twelve months or no previous surgical sterilization.

Sites / Locations

University of Texas MD Anderson Cancer Center
Fred Hutchinson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Cycle # 1

Cycle #2

Arm Description

First Cycle High-dose (HD) chemotherapy followed by stem-cell infusion (PBPC) HD Cycle #1: Gemcitabine/Docetaxel/Melphalan/Carboplatin + PBPC

Second Cycle High-dose (HD) chemotherapy followed by stem-cell infusion (PBPC) HD Cycle #2: Ifosfamide/Carboplatin/Etoposide + PBPC

Outcomes

Primary Outcome Measures

2-year Event-Free Survival (EFS)

Event-free survival estimated from the first day of High-Dose Course Cycle #1 (Day -6) until tumor progression, relapse, or death from any cause.

Secondary Outcome Measures

Full Information

NCT ID

NCT00936936

First Posted

July 8, 2009

Last Updated

October 4, 2023

Sponsor

M.D. Anderson Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT00936936

Brief Title

High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors

Official Title

High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 2, 2009 (Actual)

Primary Completion Date

March 15, 2024 (Anticipated)

Study Completion Date

March 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The goal of this clinical research study is to learn if 2 cycles of high-dose chemotherapy can help to control germ-cell tumors. The first cycle of chemotherapy will include the drugs gemcitabine, docetaxel, melphalan, and carboplatin. The second cycle of chemotherapy will include the drugs ifosfamide, carboplatin, and etoposide. The safety of these drug combinations will also be studied. This is an investigational study. Gemcitabine, docetaxel, melphalan, ifosfamide, carboplatin, and etoposide are all FDA-approved and commercially available for the treatment of germ-cell tumors. Up to 67 patients will be enrolled in this study.

Detailed Description

The Study Drugs: Carboplatin, melphalan, and ifosfamide are designed to damage the DNA (the genetic material) of cancer cells, which may cause the cancer cells to die. Docetaxel and etoposide are designed to stop the growth of cancer cells, which may cause the cancer cells to die. Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may also help docetaxel, carboplatin, and melphalan to be more effective by stopping tumor cells from repairing damage caused by these drugs. Study Drug Administration: You will receive 2 cycles of high-dose chemotherapy with stem-cell support, 1-2 months apart. Starting on the first day of your hospital stay, you will begin gargling and swishing Caphosol and Glutamine in your mouth 4 times a day. This is done to help prevent mouth and throat sores. On Day 2 of your stay in the hospital, through the CVC, you will receive gemcitabine over 4 hours and docetaxel over 2 hours. On Days 3-5, through the CVC, you will receive gemcitabine over 4 hours, melphalan over 15 minutes, and carboplatin over 2 hours. On Day 6, you will not receive any study drugs. On Day 7, you will receive the stem cells through the CVC over about 30-60 minutes. As part of standard care, you will receive G-CSF (filgrastim) as an injection under your skin daily, starting 5 days after the transplant, until your blood cell levels return to normal. As part of standard mouth care you will be asked to do mouthwashes 4 times a day with caphosol (artificial saliva) and glutamine. Two (2) to 4 weeks after you leave the hospital after Cycle 1, you will receive your second cycle of high-dose chemotherapy. On Days 2-4 of your stay in the hospital, through the CVC, you will receive ifosfamide over 6 hours, etoposide over 2 hours, and carboplatin over 2 hours. On Days 5-6, you will not receive any study drugs. On Day 7, you will receive the stem cells through the CVC over about 30-60 minutes. Study Visits: About 1 month, 100 days, 6 months and 1 year after your second stem cell transplant, the following tests and procedures will be performed: To check the status of the disease, you will have CT scans of your chest, abdomen, and pelvis. Blood (about 3 tablespoons) will be drawn for routine tests. Length of Study: You will be off study after about 1 year from your second transplant. You will be taken off study early if the disease gets worse or if you experience any intolerable side effects. Long-Term Follow-up: If your doctor thinks it is needed, you may have follow-up visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Testicular Cancer

Keywords

Testis, Relapsed Testicular Cancer, Bevacizumab, Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF, Carboplatin, Paraplatin, Docetaxel, Taxotere, Etoposide, VePesid, Gemcitabine, Gemcitabine Hydrochloride, Gemzar, Ifosfamide, Ifex, Melphalan, Alkeran

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

64 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cycle # 1

Arm Type

Experimental

Arm Description

First Cycle High-dose (HD) chemotherapy followed by stem-cell infusion (PBPC) HD Cycle #1: Gemcitabine/Docetaxel/Melphalan/Carboplatin + PBPC

Arm Title

Cycle #2

Arm Type

Experimental

Arm Description

Second Cycle High-dose (HD) chemotherapy followed by stem-cell infusion (PBPC) HD Cycle #2: Ifosfamide/Carboplatin/Etoposide + PBPC

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemcitabine Hydrochloride, Gemzar

Intervention Description

1800 mg/m^2 IV over 3 hours on Days -5 to Day -2.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Taxotere

Intervention Description

Docetaxel 300 mg/m^2 IV over 2 hours on Day -5.

Intervention Type

Drug

Intervention Name(s)

Melphalan

Other Intervention Name(s)

Alkeran

Intervention Description

50 mg/m^2 IV over 15 minutes on Days -4 to Day -2.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Paraplatin

Intervention Description

Cycle 1: 333 mg/m^2 IV over 2 hours on Days -4 to -2. Cycle #2: 300 mg/m^2 IV over 2 hours on Days -6 to -3.

Intervention Type

Drug

Intervention Name(s)

Mesna

Other Intervention Name(s)

Mesnex

Intervention Description

3,000 mg/m^2 per day in 96-hour continuous infusion, starting 30 minutes prior to the first dose of ifosfamide, on Days -6 to -4.

Intervention Type

Drug

Intervention Name(s)

Ifosfamide

Other Intervention Name(s)

Ifex

Intervention Description

3,000 mg/m^2 IV over 6 hours on Days -6 to -3

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

VePesid

Intervention Description

200 mg/m^2 IV over 3 hours, every 12 hours on Days -6 to -4.

Intervention Type

Procedure

Intervention Name(s)

Stem Cell Transplant

Other Intervention Name(s)

SCT, Hematopoietic progenitor-cell infusion, PBPC

Intervention Description

Stem cell infusion on Day 0.

Primary Outcome Measure Information:

Title

2-year Event-Free Survival (EFS)

Description

Event-free survival estimated from the first day of High-Dose Course Cycle #1 (Day -6) until tumor progression, relapse, or death from any cause.

Time Frame

2 Years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female patients, age 12 to 65 years. Patients with seminomatous or nonseminomatous germ-cell tumors (GCT) in one of the following groups: A) First relapse or progression or second response with an intermediate or high risk according to the Beyer model. B) Second relapse or beyond. Adequate renal glomerular and tubular function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL, and urinary protein excretion </=500 mg/day. Adequate hepatic function, as defined by ALT and AST </=3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase </=2 x ULN or considered not clinically significant. Adequate pulmonary function with FEV1 (Forced expiratory volume in the first second), FVC (Forced vital capacity) and DLCO (diffusing capacity of the lung for carbon monoxide) >/=50% of predicted, corrected for volume and hemoglobin. Adequate cardiac function with LVEF (left ventricular ejection fraction) >/=40%. No uncontrolled arrhythmias or symptomatic cardiac disease. Zubrod performance status 0-2. A minimum apheresis collection of 5 million CD34+ cells/kg of autologous hematopoietic progenitor cells (AHPC). Written informed consent by patients and/ or their parents or legal guardians. Assent for those patients inclusive of ages 12 to 17. Exclusion Criteria: Growing teratoma syndrome, defined as enlarging tumor masses with normal serum markers during chemotherapy for nonseminomatous GCT. Major surgery within 30 days before the initiation of study treatment Radiotherapy within 21 days prior to initiation of study treatment Prior whole brain irradiation. Patients with active central nervous system (CNS) disease, defined as brain or meningeal metastases that are not in complete remission. Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/=10,000 copies/mL, or >/= 2,000 IU/mL). Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients who either show chronic hepatitis C or positive hepatitis C serology. Active infection requiring parenteral antibiotics. HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts Patients who have had a previous autologous or allogeneic stem cell transplant in the previous 12 months. Positive pregnancy test in a female patient of childbearing potential defined as not post menopausal for twelve months or no previous surgical sterilization.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yago Nieto, MD, PHD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77007

Country

United States

Facility Name

Fred Hutchinson Cancer Center

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26199392

Citation

Nieto Y, Tu SM, Bassett R, Jones RB, Gulbis AM, Tannir N, Kingham A, Ledesma C, Margolin K, Holmberg L, Champlin R, Pagliaro L. Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors. Ann Oncol. 2015 Oct;26(10):2125-32. doi: 10.1093/annonc/mdv310. Epub 2015 Jul 21. Erratum In: Ann Oncol. 2015 Dec;26(12):2507-8.

Results Reference

derived

Links:

URL

http://www.mdanderson.org

Description

University of Texas MD Anderson Cancer Center Website

Learn more about this trial

High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors

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