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Advanced CancersPhase 1NCT01430572

Pazopanib and Everolimus in PI3KCA Mutation Positive/PTEN Loss Patients

A Phase 1 study testing Pazopanib and Everolimus 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 Votrient (pazopanib) and Afinitor (everolimus) that can be given to patients with advanced cancer. The safety of these drugs will also be studied. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Advanced Cancers, Solid Tumors
What is being tested?
Pazopanib and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteUnited States
Study dates
7 Oct 2011to 12 May 2020
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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
  • Patients with advanced or metastatic solid tumors that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
  • Patients must have been off previous chemotherapy or radiotherapy for two weeks prior to start of treatment. For biologic/targeted therapies, patients must be >/= five half-lives or >/= 2 weeks from the last treatment dose, whichever comes first. Patients may have received palliative localized radiation immediately before (or during) treatment provided radiation is not delivered to the single target lesion available.
  • ECOG performance status </= 2.
  • Abnormal organ function is permitted. However, patients must meet the following criteria: neutrophil count >/= 1.5 x 10*9/L; platelets >/= 100 x 10*9/L; creatinine </= 1.5 X upper limit of normal (ULN); T. bilirubin </= 1.5 X ULN; AST(SGOT) and/or ALT(SGPT) </= 2.5 X ULN, UPC < 1.
  • Women of child-bearing potential MUST have a negative serum or urine HCG test within 14 days of first dose. Sexually active patients must agree to use contraception for the duration of study participation: women, 2 weeks before the first treatment dose and for 28 days after the last dose; and men, from the first treatment dose and for 28 days after the last dose of treatment. For the purpose of this protocol women of child-bearing potential are defined as: a female able to have children that has not been surgically sterilized or that has not been without menses for 12 consecutive months.
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  • Patients must be >/=16 years of age.
  • Fresh blood samples must be provided for all subjects for biomarker analysis before treatment with investigational product.
  • Patients must have evaluable disease by RECIST criteria.
  • For the dose expansion cohort patients will have to have any kind of genomic alteration in either PI3K and/or PTEN of their tumor.

Who cannot join

  • Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anti-convulsants in prior 2 weeks.
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:Active peptic ulcer disease; Known intraluminal metastatic lesion/s with risk of bleeding; Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease),or other gastrointestinal conditions with increased risk of perforation; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior beginning study treatment.
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to; Malabsorption syndrome; Major resection of the stomach or small bowel
  • Corrected QT (QTc) > 480 msecs.
  • History of any one or more of the following cardiovascular conditions within the past 6 months:Cerebrovascular accident, Myocardial infarction, Unstable angina , Cardiac angioplasty or stenting, Coronary artery bypass graft surgery, Class III or IV heart failure, as defined by the New York Heart Association (NYHA), Untreated pulmonary embolism (PE) or deep venous thrombosis (DVT). Note: subjects with recent PE or DVT who have been therapeutically coagulated for at least 6 weeks are eligible.
  • Uncontrolled systemic vascular hypertension (systolic blood pressure >/= 140 mmHg, diastolic blood pressure >/= 90 mmHg). Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic BP and mean systolic BP. The mean SBP/DBP ration must be < 140/90.
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  • Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
  • Evidence of active bleeding or bleeding diathesis.
  • Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage. Note: Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions). Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed. Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.
  • Recent hemoptysis (>/= ½ teaspoon of red blood within 8 weeks before first dose of study drug).
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment.
  • Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
  • Prior malignancy Note: Subjects who have had another malignancy and have been disease-free for 2 years, and/or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.

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: Phase I Combination of Pazopanib and Everolimus in PI3KCA Mutation Positive/PTEN Loss Patients With Advanced Solid Tumors Refractory to Standard Therapy

The goal of this clinical research study is to find the highest tolerable dose of the combination of Votrient (pazopanib) and Afinitor (everolimus) that can be given to patients with advanced cancer. The safety of these drugs will also be studied.

Pazopanib is designed to block different receptors in the cancer cells that ultimately are responsible for the growth of the tumor and its blood vessels.

Everolimus is designed to block a protein called mTOR inside the cancer cells, which is also involved in cancer growth.

Read the detailed description

Study Groups:

Dose Escalation:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of the combination of pazopanib and everolimus based on when you joined this study. Up to 8 dose levels of pazopanib and everolimus will be tested. Up to 6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group 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 pazopanib and everolimus is found.

Expansion:

Once the highest tolerable dose of pazopanib and everolimus is found, up to 14 more participants may be enrolled to further study the safety of the drugs at that dose and the efficacy of the drugs in a certain tumor group.

Study Drug Administration:

Each study cycle is 28 days.

Pazopanib and everolimus are taken by mouth on an empty stomach (1 hour before meals or 2 hours after meals).

On Days 1-5 of Cycle 1 only, you will take pazopanib and everolimus together. First take pazopanib and then take everolimus.

After those first 5 days, you will take pazopanib and everolimus every other day separately. Starting Day 6 of Cycle 1, pazopanib will be taken every even day (6, 8, 10, and so on) . Everolimus will be taken every odd day (7, 9, 11, and so on).

Beginning with Cycle 2, you will take pazopanib every even day (2, 4, 6, and on so) and everolimus every odd day (3, 5, 7, and so on).

Study Visits:

At each study visit, you will be asked what about any drugs or herbal supplements that you may be taking and if you have had any side effects.

On Day 1 of Cycle 1:

  • Your medical history will be recorded if it has been more than 3 days since screening.
  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.
  • You will have an ECG.
  • Blood (about 2 teaspoons) and urine will be collected for routine tests and hepatitis screening.

On Days 8, 15, and 22 of Cycle 1:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Blood (about 2 teaspoons) and urine will be collected for routine tests.

On Day 1 of Cycles 2 and beyond:

  • 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.
  • You will have an ECG.

On Day 15 of Cycle 2:

° Blood (about 2 teaspoons) will be collected for routine tests.

Every 8 weeks:

  • You will have a CT scan, x-ray, MRI scan, and/or PET scan to check the status of the disease.
  • Blood (about 1 teaspoon) may be drawn for tumor marker testing.
  • If you are able to become pregnant, you will have a blood (about ½ teaspoon) or urine pregnancy test.

PK testing:

At least 6 participants in the expansion part of the study will have blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing. The study staff will tell you if you will have this testing. PK testing measures the amount of study drug in the body at different time points.

  • On Day 5 of Cycle 1 and Days 1 and 2 of Cycle 2, blood will be drawn before and 8 more times up to 10 hours after taking the study drugs.
  • On Day 2 of Cycle 2, blood will be drawn 1 more time for PK testing after 24 hours of taking everolimus. If you could not have the 10 hour draw the day before, this will be drawn at this day.
  • On Day 6 of Cycle 1 and Day 3 of Cycle 2, blood will be drawn 1 time for PK testing after 24 hours of taking pazopanib. If you could not have the 10 hour draw the day before, this will be drawn at this day.
  • Blood will be drawn 1 time at the end-of-dosing visit.

Length of Study:

You may continue taking the study drugs for as long as you are benefitting. You will be taken off study early if the disease gets worse, intolerable side effects occur, you develop new health problems, or your doctor thinks that it is no longer in your best interest to receive the study drug.

End-of-Dosing Visit:

Within 4 weeks after your last dose of 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.
  • If you are able to become pregnant, you will have a blood (about 1 teaspoon) or urine pregnancy test.

This is an investigational study. Pazopanib is FDA approved and commercially available for the treatment of advanced renal cancer and certain types of advanced soft tissue sarcoma but has not been approved for use in other cancer types. Everolimus is FDA approved and commercially available for the prevention of kidney transplant rejection, to treat advanced renal cancer, and to treat subependymal giant cell astrocytoma associated with tuberous sclerosis.

The combination of pazopanib and everolimus to treat advanced cancer is investigational.

Up to 62 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Being tested
Pazopanib, Everolimus
Keywords
Advanced Cancers, Solid Tumors, PI3KCA Mutation Positive/PTEN, Refractory to standard therapy, Relapsed after standard therapy, Pazopanib, GW786034, Everolimus, Afinitor, RAD001

What participants receive

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

  • PazopanibDrug

    Also called GW786034

    Starting Dose: 200 mg by mouth on Days 1 - 5 of Cycle 1 only. On Day 6 and every cycle-day with an even number, only pazopanib administered.

  • EverolimusDrug

    Also called Afinitor, RAD001

    Starting dose: 5.0 mg by mouth on Days 1 - 5 of Cycle 1. On Day 7 and every cycle-day with an odd number, only everolimus will be administered.

    Dose Expansion Phase: Maximum tolerated dose (MTD) from lead in phase.

Study groups in NCT01430572
Study groupRoleWhat they receive
Pazopanib + EverolimusExperimentalPazopanib 200 mg and Everolimus 5.0 mg oral dosing every other day (except for lead in 5 days of Cycle 1 where both drugs administered daily).
Receives: Drug: Pazopanib; Drug: Everolimus

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Pazopanib and Everolimus

    MTD defined as highest dose studied in which the incidence of Dose Limiting Toxicity (DLT) was less than 33%, with no more than 1 of 6 evaluable participants had a DLT using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

    Measured: 28 days

Secondary outcomes (3)
  1. Response.of Pazopanib and Everolimus

    Response evaluated using following criteria: Stable disease for more than or equal to 4 months.

    Measured: 4 months

  2. Response.of Pazopanib and Everolimus

    Response evaluated using following criteria: Decrease in measurable tumor (target lesions) by more than or equal to 20% by RECIST criteria.

    Measured: 4 months

  3. Response.of Pazopanib and Everolimus

    Response evaluated using following criteria: Decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in PSA for patients with prostate cancer.

    Measured: 4 months

Timeline

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

  1. First posted8 Sep 2011 (estimated)
  2. Study start7 Oct 2011
  3. Primary completion12 May 2020
  4. Study completion12 May 2020

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
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01430572
Sponsor's protocol ID
2011-0322
Other IDs
NCCN-GSKP05, NCI-2011-03040
Status last verified
Jun 2023
First submitted
6 Sep 2011
Last updated
6 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pazopanib and Everolimus 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 10 inclusion and 14 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 6 Jun 2023. 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 Pazopanib and Everolimus (time frame: 28 days). 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 6 Jun 2023.

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