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A Phase I Dose-Escalation Study of Erlotinib in Combination With Pralatrexate in Subjects With Advanced Cancer


Phase 1
12 Years
N/A
Open (Enrolling)
Both
Advanced Cancers, Solid Tumors

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Trial Information

A Phase I Dose-Escalation Study of Erlotinib in Combination With Pralatrexate in Subjects With Advanced Cancer


Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of erlotinib and pralatrexate based on when you join this study.

Dose Escalation:

Several dose levels of erlotinib and pralatrexate will be tested. Three (3) to 6
participants will start at the lowest planned doses of erlotinib and pralatrexate. Each new
group of 3-6 participants will receive a higher dose than the group before it, if no
intolerable side effects were seen. This will continue until the highest tolerable dose of
erlotinib in combination with pralatrexate is found.

Dose Expansion:

Once the highest tolerable dose or most appropriate combination dose level is found, 10 more
participants will take the study drugs at this dose level.

Study Drug Administration:

Each study cycle is 28 days.

Up to 10 days before you start treatment , you will start taking folic acid to help lower
the risk of side effects. Although the study drug is designed to prevent the body from
making folic acid that could help cancer grow and spread, some folic acid is needed to
prevent side effects in non-cancerous tissue. You will take folic acid by mouth 1 time
every day during treatment and for at least 30 days after you received the last dose of
pralatrexate.

Up to 10 days before you start treatment, you will receive a vitamin B12 injection. You will
receive an injection of Vitamin B12 about every 3 months after that.

On Days 1, 8, and 15 of each cycle, you will receive pralatrexate by vein over 3-5 minutes.

You will take erlotinib hydrochloride by mouth 1 time a day every day. You should take
erlotinib hydrochloride on an empty stomach either 1 hour before eating or 2 hours after
eating.

You will take erlotinib at home except on the days when you have a study visit. You should
take it at about the same time each day with about a cup (8 ounces) of water.

Study Visits:

At every study visit, you will be asked about any current health conditions you have, any
other drugs you are taking, and if you have had any side effects.

If the screening tests were performed within 7 days before Cycle 1, tests and procedures may
not have to be repeated.

At any time during Cycle 1:

- You will have a physical exam, including measurement of your weight at least 1 time per
cycle.

- Your vital signs will be measured.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests and to see how well your
blood clots.

- If you are taking part in the expansion phase, blood (about 2 teaspoons) will be drawn
for PD testing.

At any time during Cycle 2:

- You will have a physical exam, including measurement of your weight at least 1 time per
cycle.

- Your vital signs will be measured.

- Your performance status will be recorded.

- Blood (about 4 teaspoons) will be drawn for routine tests.

- If you are taking part in the expansion phase, blood (about 2 teaspoons) will be drawn
for PD testing.

About every 8 weeks, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check
the status of the disease. Blood (about 1 teaspoon) may be drawn for tumor marker testing
depending on the type of tumor. If the study doctor thinks it is needed, they will be
performed more or less often.

At any time during Cycle 3 and beyond:

- You will have a physical exam, including measurement of your weight at least 1 time per
cycle.

- Your vital signs will be measured.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) will be drawn for routine tests.

Length of Dosing:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment
and follow-up visits.

End of Dosing Visit:

After you are finished taking the study drugs:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

This is an investigational study. Pralatrexate is FDA approved and commercially available
for the treatment of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma
(PTCL). Erlotinib is FDA approved and commercially available for the treatment of pancreatic
cancer and non small cell lung cancer (NSCLC). The study drug combination is
investigational.

Up to 74 patients will take part in this study. All will be enrolled at MD Anderson.


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. ECOG performance status /= 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) 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 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 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

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 CTC 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 the NCI-CTCAE that is attributable to therapy.

Outcome Time Frame:

8 weeks

Safety Issue:

Yes

Principal Investigator

Jennifer J. Wheler, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2011-0916

NCT ID:

NCT01532011

Start Date:

March 2012

Completion Date:

Related Keywords:

  • Advanced Cancers
  • Solid Tumors
  • Advanced Cancers
  • Solid Tumors
  • Erlotinib
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva
  • Pralatrexate
  • Folotyn
  • PDX-010
  • Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030