We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Erlotinib in Combination With Pralatrexate in Advanced Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01532011
Recruitment Status : Completed
First Posted : February 13, 2012
Last Update Posted : July 4, 2016
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of the combination of erlotinib and pralatrexate that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.

Pralatrexate is designed to block the body's ability to make folic acid, a protein that may help cancer tissue to develop and spread.

Erlotinib hydrochloride is designed to block proteins that are thought to cause cancer cells to grow. Erlotinib may help slow the growth of tumors.

Condition or disease Intervention/treatment Phase
Advanced Cancers Solid Tumors Drug: Erlotinib Drug: Pralatrexate Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose-Escalation Study of Erlotinib in Combination With Pralatrexate in Subjects With Advanced Cancer
Study Start Date : March 2012
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Erlotinib + Pralatrexate

Dose escalation group starting dose: Erlotinib 75 mg by mouth daily for a 28 day cycle. Starting dose of Pralatrexate 15 mg/m2 by vein on days 1, 8, and 15 of a 28 day cycle.

Dose expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.

Drug: Erlotinib

Dose escalation group starting dose: 75 mg by mouth daily for a 28 day cycle.

Dose expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.

Other Names:
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva

Drug: Pralatrexate

Dose escalation group starting dose: 15 mg/m2 by vein on days 1, 8, and 15 of a 28 day cycle.

Dose expansion group starting dose: Maximum tolerated dose (MTD) from dose escalation group.

Other Names:
  • Folotyn
  • PDX-010

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Erlotinib with Pralatrexate [ Time Frame: 8 weeks ]
    MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0. Grade 4 hematologic toxicity lasting 2 weeks or longer despite supportive care. Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity, including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in NCI-CTCAE as attributable to therapy.

Secondary Outcome Measures :
  1. Tumor Response [ Time Frame: 8 weeks ]
    Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in CA125 for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in tumor density, as measured in Hounsfield units (HU), by more than or equal to 15% (28).

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Measurable or non-measurable disease.
  2. Patients with advanced cancer should be refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that improves survival by at least three months.
  3. Patients must be at least 3 weeks after cytotoxic therapy and at least 5 half lives after their previous treatment or 3 weeks, whichever shorter, after biologic therapy. Patients may receive palliative radiotherapy immediately before or during treatment provided that not all target lesions are radiated.
  4. Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
  5. Patients must have normal organ and marrow function defined as: absolute neutrophil count >/=1,000/mL; platelets >/=100,000/mL; creatinine < 2.0; total bilirubin < 2.0; ALT(SGPT) </=3 X upper limit of normal (ULN); Exception for patients with liver metastasis: ALT(SGPT) </= 5 X ULN.
  6. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
  7. Ability to understand and the willingness to sign a written informed consent document.
  8. For the MTD expansion cohort, patients will be eligible if they meet one of the following criteria: I. Have an epidermal growth factor receptor (EGFR)-sensitive mutation (as G719C in exon 18, E746-A750 in exon 90, L858R in exon 21) and have been previously treated with EGFR inhibitor therapy but have subsequently developed resistance, OR II. Have an EGFR-resistant mutation (as T790M in exon 20), OR III. Do not have an EGFR mutation, but have benefited from EGFR inhibitor therapy (including either >/=4 months of stable disease [SD] OR a >/= partial response [PR]).
  9. Age >/= 12 years

Exclusion Criteria:

  1. Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection requiring hospitalization; psychiatric illness/social situations that would limit compliance with study requirements.
  2. Exclusion of patients with creatinine >2.0 and bilirubin > 2.0.
  3. Patients with colorectal carcinoma with tumors that demonstrate a Kirsten rat sarcoma (KRAS) mutation.
  4. Pregnant or lactating women.
  5. Patients with a history of bone marrow transplant within the previous two years.
  6. Patients with a known hypersensitivity to any of the components of the drug products.
  7. Patients with major surgery within 30 days prior to entering the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01532011

Layout table for location information
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Layout table for investigator information
Principal Investigator: Shumei Kato, MD M.D. Anderson Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01532011    
Other Study ID Numbers: 2011-0916
NCI-2012-00219 ( Registry Identifier: NCI CTRP )
First Posted: February 13, 2012    Key Record Dates
Last Update Posted: July 4, 2016
Last Verified: July 2016
Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Solid Tumors
Erlotinib Hydrochloride
Additional relevant MeSH terms:
Layout table for MeSH terms
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action