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

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborators:	New York University Cancer Institute New York University Medical Center New York University School of Medicine National Comprehensive Cancer Network
Information provided by (Responsible Party):	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01183065

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:

MedlinePlus related topics: B Vitamins Cancer Head and Neck Cancer

Drug Information available for: Folic acid Cyanocobalamin Vitamin B Complex Hydroxocobalamin Pralatrexate

U.S. FDA Resources

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.

Estimated Enrollment:	14
Study Start Date:	August 2010
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2013 (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.

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

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 Medical Center

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:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

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 17, 2012
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:

Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Folic Acid
Vitamin B 12
Hydroxocobalamin
Vitamin B Complex

Hematinics
Vitamins
Aminopterin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematologic Agents
Therapeutic Uses
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2012