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

NCT00936936 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2008-0378NCI-2011-01631
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With 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.

  2 Years

Secondary Outcomes (1)

• Overall Survival

  1 year post treatment

Study Arms (2)

Cycle # 1

EXPERIMENTAL

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

Drug: Gemcitabine; Drug: Docetaxel; Drug: Melphalan; Drug: Carboplatin; Procedure: Stem Cell Transplant

Cycle #2

EXPERIMENTAL

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

Drug: Carboplatin; Drug: Mesna; Drug: Ifosfamide; Drug: Etoposide; Procedure: Stem Cell Transplant

Interventions

Gemcitabine DRUG

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

Also known as: Gemcitabine Hydrochloride, Gemzar

Cycle # 1

Docetaxel DRUG

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

Also known as: Taxotere

Cycle # 1

Melphalan DRUG

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

Also known as: Alkeran

Cycle # 1

Carboplatin DRUG

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.

Also known as: Paraplatin

Cycle # 1; Cycle #2

Mesna DRUG

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.

Also known as: Mesnex

Cycle #2

Ifosfamide DRUG

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

Also known as: Ifex

Cycle #2

Etoposide DRUG

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

Also known as: VePesid

Cycle #2

Stem Cell Transplant PROCEDURE

Stem cell infusion on Day 0.

Also known as: SCT, Hematopoietic progenitor-cell infusion, PBPC

Cycle # 1; Cycle #2

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77007, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 26199392 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Testicular Neoplasms

Interventions

Gemcitabine; Docetaxel; Melphalan; Carboplatin; Mesna; Ifosfamide; Etoposide; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Coordination Complexes; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Cyclophosphamide; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Oxazines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Yago Nieto, PhD. / Stem Cell Transplantation Department
• Organization: University of Texas MD Anderson Cancer Center

ynieto@mdanderson.org

713-792-8750

Study Officials

• Yago Nieto, MD, PHD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2009
• First Posted: July 10, 2009
• Study Start: June 2, 2009
• Primary Completion: January 11, 2024
• Study Completion: January 11, 2024
• Last Updated: August 26, 2024
• Results First Posted: August 26, 2024

Record last verified: 2024-08

Locations

US (2)