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Advanced CancerPhase 1NCT01339871

Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies

A Phase 1 study testing Pazopanib and Vorinostat in people with Advanced Cancer, 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 pazopanib and vorinostat 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 18 years and older
Conditions the study is for
Advanced Cancer
What is being tested?
Pazopanib and Vorinostat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
152 participants
Where
1 siteUnited States
Study dates
20 Apr 2011to 7 Jun 2017
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available.
  • Patients must have measurable or evaluable disease, as defined by RECIST 1.1.
  • Men or women aged >/= 18 years. However, patients who are 13 years old or older and have more than 45 kg of body weight will be eligible after consultation with their pediatric attending since the doses of these agents are the fixed doses.
  • Women of child-bearing potential and men must agree to use adequate contraception.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Adequate organ functions: Neutrophils > 1000/uL, Platelets >/= 75,000/uL, Total bilirubin </= 2 x upper limit of normal (ULN) (upper limit of normal), ALT </= 2.5 x ULN or </= 5 x ULN if liver metastases persist, Serum creatinine < 2 x ULN
  • Patients with either previous vascular endothelial growth factor (VEGF) inhibition based treatment or previous vorinostat based treatment are eligible. However, patients who received both VEGF and histone deacetylase (HDAC) inhibition simultaneously are ineligible.
  • Specific to the cohorts as designed to enroll patients with TP53 mutations: TP53 mutations are identified by next-generation sequencing in a chemiluminescence immunoassay analyzer (CLIA)-certified laboratory prior to screening.

Who cannot join

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (NYHA Class III or IV), or unstable angina pectoris.
  • Inadequately controlled hypertension (defined as systolic blood pressure >or = 140 and/or diastolic blood pressure > or = 90 mmHg on antihypertensive medications), any prior history of hypertensive crisis or hypertensive encephalopathy, and history of myocardial infarction or unstable angina within 6 months prior to study enrollment.
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment.
  • Major surgical procedure within 28 days prior to study enrollment.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
  • History of allergic reactions to the study drugs, their analogs or any component of the products.
Show all 11Show fewer
  • Any treatment specific for tumor control within 3 weeks of study drugs; or within 2 weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted agents with half lives and pharmacodynamic effects lasting less than 5 days (that includes but is not limited to erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents). Palliative radiation immediately before or during the study is acceptable provided there is evaluable disease that has not been radiated.
  • Urine for proteinuria >/= 2+ (patients discovered to have >/= 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate </= 1g of protein in 24 hours to be eligible).
  • Patients with clinical bleeding, active gastric or duodenal ulcer.
  • Symptomatic primary tumors or metastasis of brain and/or central nervous system that are uncontrolled with antiepileptics and requiring high doses of steroids.
  • Concurrent use of antiarrythmics or contraindicated medications (including, but not limited to, cisapride, mesoridazine, pimozide, posaconazole, sparfloxacin, thioridazine).

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 Study of Pazopanib and Vorinostat in Patients With Advanced Malignancies

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

Read the detailed description

Study Drugs:

Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.

Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, up to 12 dose levels of pazopanib and vorinostat will be tested. Three (3) to 6 participants will be enrolled at each dose level of the combination of pazopanib and vorinostat. The first group of participants will receive the lowest dose level of pazopanib and vorinostat. Each new group(s) will receive a higher combination dose of pazopanib and vorinostat than the group before it, if no intolerable side effects were seen. Participants may be enrolled on 1-3 similar dose levels of pazopanib and vorinostat at the same time. You will be assigned to a dose level based on when you joined this study. This will continue until the highest tolerable dose(s) of the study drug combination is found.

The dose of the study drug combination that you receive may be lowered if you have intolerable side effects.

Once the highest tolerable dose of pazopanib and vorinostat is found, this combination dose will be given to an expansion group of 14 additional participants.

Study Drug Administration:

You will take pazopanib and vorinostat by mouth 1 time each day. Note that you will not take the study drugs at the same time as each other. You should take pazopanib either 1 hour before or 2 hours after eating a meal. You should take vorinostat with food.

Study Visits:

Each study cycle is 28 days.

At all study visits, you will be asked about any drugs you may be taking and side effects you may be having.

If you are able to take your blood pressure at home, you will be asked to take your blood pressure each day while you are participating on this study.

Within 7 days before the first dose of study drugs:

  • You will have a physical exam, including measurement of your weight and vital signs (blood pressure, heart rate, temperature, and breathing rate).
  • You will be asked how well you are able to perform the normal activities of daily living (performance status).
  • 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.

Every week during Cycle 1, blood (about 1 teaspoon) will be drawn for routine tests.

During Week 1 of each cycle:

  • Your medical history will be recorded.
  • 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.

At the end of Cycle 2 and then every 2-3 cycles after that:

  • You will have a CT, MRI, positron emission tomography (PET) scan, and/or x-ray to check the status of the disease.
  • If the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to measure tumor markers.

After Cycle 6, you are only required to visit MD Anderson every 2 cycles if you get your blood draws at your local doctor at the beginning of each cycle. Talk to the study staff about this option.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will be taken off study early if the disease gets worse, or you have intolerable side effects.

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study Visit:

Within 30 days after your last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests and procedures performed:

  • Your medical history will be recorded.
  • 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 the study doctor thinks it is needed, blood (about 1 teaspoon) will be drawn to measure tumor markers.
  • If the study doctor thinks it is needed, you will have a chest x-ray, CT, MRI, and/or PET scan to check the status of the disease.

Up to 174 evaluable patients will take part in this study. All will be enrolled at MD Anderson.

Conditions
Advanced Cancer
Being tested
Pazopanib, Vorinostat
Keywords
Pazopanib, Vorinostat, Advanced Malignancies

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 400 mg orally daily of 28 day cycle.

  • VorinostatDrug

    Also called SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza

    Starting dose 100 mg orally daily of 28 day cycle.

Study groups in NCT01339871
Study groupRoleWhat they receive
Pazopanib + VorinostatExperimentalStarting doses Pazopanib 400 mg orally daily and Vorinostat 100 mg orally daily
Receives: Drug: Pazopanib; Drug: Vorinostat

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 Vorinostat

    Maximum tolerated dose defined by dose limiting toxicities (DLTs) that occur in the first 28 days. . Non-hematological toxicities are graded by using NCI CTCAE v4.0 toxicity criteria and DLT defined as treatment-related grade 3 or greater non-hematological toxicity other than nausea, vomiting, fatigue, or hypertension, drug-related grade 3 or greater electrolyte abnormalities that do not return to ≤ grade 1 or baseline within 72 hours, grade 3 nausea and vomiting related to study drug treatment that is not controlled at 72 hours despite appropriate antiemetic therapy, or grade 4 fatigue or hypertension related to study drug therapy.

    Measured: 28 days

Timeline

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

  1. First posted21 Apr 2011 (estimated)
  2. Study start20 Apr 2011
  3. Primary completion7 Jun 2017
  4. Study completion7 Jun 2017

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
152 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01339871
Sponsor's protocol ID
2011-0051
Other IDs
NCI-2011-00771
Status last verified
Jun 2017
First submitted
20 Apr 2011
Last updated
16 Jun 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Fu S, Hou MM, Naing A, Janku F, Hess K, Zinner R, Subbiah V, Hong D, Wheler J, Piha-Paul S, Tsimberidou A, Karp D, Araujo D, Kee B, Hwu P, Wolff R, Kurzrock R, Meric-Bernstam F. Phase I study of pazopanib and vorinostat: a therapeutic approach for inhibiting mutant p53-mediated angiogenesis and facilitating mutant p53 degradation. Ann Oncol. 2015 May;26(5):1012-1018. doi: 10.1093/annonc/mdv066. Epub 2015 Feb 10.

    PubMed 25669829

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pazopanib and Vorinostat in people with Advanced Cancer, 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 8 inclusion and 11 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 16 Jun 2017. 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 Vorinostat (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01339871, which also lists 1 linked publication.

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 16 Jun 2017.

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