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Advanced CancersPhase 1NCT01532011

Erlotinib in Combination With Pralatrexate in Advanced Malignancies

A Phase 1 study testing Erlotinib and Pralatrexate in people with Advanced Cancers and Solid Tumors, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Advanced Cancers, Solid Tumors
What is being tested?
Erlotinib and Pralatrexate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
1 siteUnited States
Study dates
Mar 2012to Jun 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Measurable or non-measurable disease.
  • 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.
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%).
  • 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.
  • 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.
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  • Ability to understand and the willingness to sign a written informed consent document.
  • 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]).
  • Age >/= 12 years

Who cannot join

  • 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.
  • Exclusion of patients with creatinine >2.0 and bilirubin > 2.0.
  • Patients with colorectal carcinoma with tumors that demonstrate a Kirsten rat sarcoma (KRAS) mutation.
  • Pregnant or lactating women.
  • Patients with a history of bone marrow transplant within the previous two years.
  • Patients with a known hypersensitivity to any of the components of the drug products.
  • Patients with major surgery within 30 days prior to entering the study.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

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 pharmacodynamic (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 positron emission computed tomography (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.

Being tested
Erlotinib, Pralatrexate
Keywords
Advanced Cancers, Solid Tumors, Erlotinib, Erlotinib Hydrochloride, OSI-774, Tarceva, Pralatrexate, Folotyn, PDX-010

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ErlotinibDrug

    Also called Erlotinib Hydrochloride, OSI-774, Tarceva

    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.

  • PralatrexateDrug

    Also called Folotyn, PDX-010

    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.

Study groups in NCT01532011
Study groupRoleWhat they receive
Erlotinib + PralatrexateExperimentalDose 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.
Receives: Drug: Erlotinib; Drug: Pralatrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Erlotinib with Pralatrexate

    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.

    Measured: 8 weeks

Secondary outcomes (1)
  1. Tumor Response

    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).

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Feb 2012 (estimated)
  2. Study startMar 2012
  3. Primary completionJun 2016
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01532011
Sponsor's protocol ID
2011-0916
Other IDs
NCI-2012-00219
Status last verified
Jul 2016
First submitted
9 Feb 2012
Last updated
4 Jul 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Erlotinib and Pralatrexate in people with Advanced Cancers and Solid Tumors, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Erlotinib with Pralatrexate (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jul 2016.

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