Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation for Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

This study has been completed.
Sponsor:
Collaborators:
New York University Cancer Institute
New York University School of Medicine
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01183065
First received: August 11, 2010
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to find out if the experimental drug pralatrexate with the vitamins folic acid and vitamin B12 might be an effective treatment for head and neck cancer. The reason we are doing this study is because another drug called methotrexate has been used for a long time to treat head and neck cancer patients. Pralatrexate was designed by scientists to be a new drug that works better than methotrexate. Laboratory studies have shown that pralatrexate works better than methotrexate at killing cancer cells.

Pralatrexate has already been studied in patients with other types of cancers, such as lymphoma and lung cancer. The results from those studies were promising. Pralatrexate was recently approved by the Food and Drug Administration (FDA) as a new treatment for a cancer called peripheral T cell lymphoma.


Condition Intervention Phase
Head and Neck Cancer
Drug: Pralatrexate With Vitamin B12 and Folic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Institution Phase II Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation for Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the overall response rate (CR+PR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    by RECIST version 1.1 criteria


Secondary Outcome Measures:
  • To determine the best overall response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    at the end of treatment with pralatrexate

  • To estimate median progression free survival (PFS). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To estimate median overall survival (OS). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To quantify the mRNA transcript levels of reduced folate carrier (RFC-1) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    in study patients and correlate to best overall response with pralatrexate.

  • To evaluate the impact of pralatrexate on circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    and correlate to best overall response with pralatrexate.


Enrollment: 13
Study Start Date: August 2010
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pralatrexate and vitamin supplementation
This will be an open-label, single arm, Simon optimal two-stage design phase II study.
Drug: Pralatrexate With Vitamin B12 and Folic Acid
Patients will be treated with 30 mg/m2 of pralatrexate intravenously once weekly for 3 weeks in a 4 week cycle with vitamin supplementation. Patients will take 1.0-1.25 mg oral folic acid on a daily basis. Folic acid should be initiated during the 10-day period preceding the first dose of pralatrexate and dosing will be continued during the full course of therapy and for 30 days after the last dose of pralatrexate. Patients will also receive a vitamin B12 (1 mg) intramuscular injection no more than 10 weeks prior to the first dose of pralatrexate and every 8-10 weeks thereafter. Subsequent vitamin B12 injections may be given the same day as treatment with pralatrexate.
Other Names:
  • Radiologic assessment of disease will be conducted every 1.5 to 2 cycles (approximately
  • every 6 to 8 weeks); after 6 months, radiologic studies will be performed every 2.5 to 3
  • cycles (approximately every 10 to 12 weeks) of therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histopathologically confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck, including unknown primary squamous cell carcinomas of the neck. Confirmation of biopsy/diagnosis will be performed at MSKCC or at participating sites (NYU Cancer Institute/NYU Medical Center/ Bellevue Hospital Center).
  • Patients must be at least 18 years of age.
  • ECOG performance status must be ≥ 0 or 1.
  • Disease must be measurable by RECIST version 1.1 criteria.
  • Patients must have been previously treated with systemic chemotherapy (i.e., chemotherapy and/or targeted therapies such as cetuximab for recurrent/metastatic HNSCC,.
  • At least four weeks must have elapsed from previous radiation therapy. Patients must have recovered from the acute toxic effects of treatment prior to study enrollment.
  • Patients must have adequate organ function, as follows:

Adequate bone marrow reserve: absolute neutrophil count (ANC) > 1,000 cells/mm3, platelets > 100,000 cells/mm3, and hemoglobin > 9 g/dL Hepatic: AST and ALT ≤ 3 X upper limit of normal (ULN); AST and ALT ≤ 5 X ULN if liver metastasis present; Total bilirubin ≤ 1.5 x ULN unless Gilbert's disease is present Renal: Serum creatinine ≤ 1.5 mg/dL or creatinine clearance (by either 24 hour urine collection or Cockcroft-Gault equation) > or = to 55 ml/min

  • Both women and men and members of all races and ethnic groups are eligible for this trial.
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Both men and women must agree to use a reliable method of birth control until 30 days following the last dose of study drug.

Exclusion Criteria:

  • History of any brain metastases unless resected with no evidence for > 12 weeks and not on steroids
  • Women who are lactating
  • Other active malignancy, other than indolent malignancies which the investigator determines are unlikely to interfere with treatment and safety analysis
  • Patients who have undergone an allogeneic stem cell transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01183065

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan-Kettering at Mercy Medical Center
Rockville Centre, New York, United States
Memoral Sloan Kettering Cancer Center@Phelps Memorial Hospital
Sleepy Hollow, New York, United States
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
New York University Cancer Institute
New York University School of Medicine
National Comprehensive Cancer Network
Investigators
Principal Investigator: Alan Ho, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01183065     History of Changes
Other Study ID Numbers: 10-112
Study First Received: August 11, 2010
Last Updated: April 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Pralatrexate
Vitamin B12
Folic Acid
10-112

Additional relevant MeSH terms:
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Neoplasms by Site
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Vitamins
Folic Acid
Vitamin B 12
Hydroxocobalamin
Vitamin B Complex
Aminopterin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014