Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes

NCT00953420 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 25145-CADENCADEN
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

Patients have a type of cancer called nasopharyngeal carcinoma (NPC) that has either come back or not gone away after the best known standard treatments. Most patients that respond to chemotherapy once their NPC tumors have come back have been treated with a platinum-based medication like cisplatin. However, since many patients are given cisplatin during their initial treatment for NPC, in this study, they will be treated with another platinum-based chemotherapy medicine that has been used in patients with NPC called carboplatin. In this study, carboplatin will be used in combination with another drug called docetaxel. Other studies in patients with advanced head and neck cancer have shown that docetaxel can cause tumors to respond better and allow patients to survive longer when added to the standard treatments for those diseases. Some patients with NPC show evidence of infection with the virus that causes infectious mononucleosis, known as the Epstein Barr virus (EBV), before or at the time of their cancer diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage disease, suggesting that it may play a role in causing NPC. Previously, patients have been treated with high-risk NPC using EBV-specific cytotoxic T cells. These cells are grown in the laboratory and taught to recognize and attack EBV infected cells. In the past, patients were either given the cells alone or just after they had received a medication to briefly lower their white blood cell count. In both cases, many patients had their tumors shrink and in some cases completely disappear after being treated with these EBV-specific cytotoxic T cells. Investigators have now decided to look at how patients with NPC and their tumors respond to the treatment combination of chemotherapy and EBV-CTL. Patients are being asked to participate in this study since the NPC tumor is associated with EBV and has either come back or not responded to standard treatment. This combination of chemotherapy and EBV-CTLs is an investigational treatment not approved by the Food and Drug Administration. The purpose of this study is to see how relapsed or refractory, EBV-associated NPC tumors respond when treated with carboplatin and docetaxel followed by EBV-CTL.

Conditions

Nasopharyngeal Carcinoma

Keywords

nasopharyngeal carcinoma; Carboplatin; Docetaxel; Epstein-Barr Virus; T Lymphocytes; EBV-CTLs

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of the study is to evaluate the overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy and immunotherapy.

  The overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy (treatment with docetaxel and carboplatin) followed by immunotherapy with EBV-specific Cytotoxic T lymphocytes will be measured. Response rates will be estimated as the percent of patients whose best response is a CR or PR, and a 95% confidence interval will be calculated for the fraction of responses obtained.To measure the overall response rate, disease will be determined by imaging (MRI, CT, and/or PET imaging) 8 weeks after immunotherapy. In addition, per standard of care, disease re-evaluation will continue 3 months during the first year after participation and then as clinically indicated per the patient's primary oncologist.

  3 months

Secondary Outcomes (2)

• Response to re-induction chemotherapy

  8 weeks

• Evaluation of immune response by measuring EBV-DNA levels

  8 weeks

Study Arms (1)

Chemotherapy and Immunotherapy

EXPERIMENTAL

1. Docetaxel 60 mg/m2 IV on Day 1 2. Carboplatin with target AUC of 5 (mg/ml x min) on Day 1 3. Dexamethasone 5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1 4. After cycle 1, subsequent cycles of chemotherapy may start once ANC \> 1000 and platelets \> 100,000 post nadir 5. Up to an additional 2 cycles of chemotherapy, given per the above schedule, may be given if the EBV-specific cytotoxic T lymphocytes product is not available after the initial 4 cycles

Drug: Docetaxel; Drug: Carboplatin; Drug: Dexamethasone; Biological: EBV-specific cytotoxic T lymphocytes; Biological: G-CSF or Peg-GCSF

Interventions

Docetaxel DRUG

60 mg/m2 IV on Day 1

Also known as: Taxotere

Chemotherapy and Immunotherapy

Carboplatin DRUG

Target AUC of 5 (mg/ml x min) on Day 1

Also known as: Paraplatin

Chemotherapy and Immunotherapy

Dexamethasone DRUG

5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1

Also known as: Decadron

Chemotherapy and Immunotherapy

EBV-specific cytotoxic T lymphocytes BIOLOGICAL

1 x 10e8 cells/m2 IV over 1 to 5 min

Also known as: EBV-specific cytotoxic T lymphocytes 1 x 10e8 cells/m2 IV

Chemotherapy and Immunotherapy

G-CSF or Peg-GCSF BIOLOGICAL

If needed per dose modification guidelines: Peg-GCSF 0.1 mg/kg ≤ 45 kg; 6 mg for \> 45 kg subcutaneous on Day 2 or GCSF 5 mcg/kg/day (max of 600 mcg) subcutaneous to start 24 hours after carboplatin administration until ANC \> 2500 cells/ul x 2 days after nadir.

Also known as: Filgrastim or pegylated filgrastim

Chemotherapy and Immunotherapy

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Nasopharyngeal Carcinoma in first or subsequent relapse or with primary refractory disease in whom the EBV-genome or antigens have been demonstrated in tissue biopsy samples
• Age 10 years or older
• Life expectancy of 8 weeks or more
• Karnofsky or Lansky score of 50 or more
• Normal bilirubin level (per institutional standard)
• AST and ALT 1.5 x or less upper limit of normal
• Alk Phos level less than 2.5 x upper limit of normal
• ANC greater than 1500 cells/ul
• Hgb 8.0 or greater
• Platelets 100,000 cells/ul or more
• Creatinine 2 x or less ULN or GFR 50 ml/min/1.73 m2 or more
• Women of child-bearing potential must take/use effective birth control while participating in the study.

You may not qualify if:

• Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded from this research.
• Prior allergic reaction to the study drugs used in this protocol or other drugs formulated with polysorbate 80.
• Known HIV positive subjects since treatment may be significantly immunosuppressive
• Women who are breast-feeding
• Severe intercurrent infection
• Patients, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• M.D. Anderson Cancer Center: collaborator

Study Sites (3)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Epstein-Barr Virus Infections

Interventions

Docetaxel; Carboplatin; Dexamethasone; Calcium Dobesilate; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Chrystal U Louis, MD, MPH

  Texas Children's Hospital; Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Pediatrics-Hem-Onc Cell & Gene

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: November 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: July 1, 2015
• Last Updated: August 18, 2017

Record last verified: 2017-08

Locations

US (3)