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Solid TumorsPhase 1NCT01528046

Metformin in Children With Relapsed or Refractory Solid Tumors

A Phase 1 study testing Vincristine, Irinotecan and Temozolomide in people with Solid Tumors and Primary Brain Tumors, run by H. Lee Moffitt Cancer Center and Research Institute at 14 sites 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 purpose of this study is to evaluate the tolerability and safety of escalating doses of metformin on a backbone of vincristine, irinotecan and temozolomide (VIT) in children with recurrent and refractory solid tumors. Read more about this study

Who is it for?
Ages 1 year to 18 years
Conditions the study is for
Solid Tumors, Primary Brain Tumors
What is being tested?
Vincristine, Irinotecan and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
14 sitesUnited States
Study dates
24 Sep 2012to 3 Feb 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 1 year to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age: Patients must be > 1 year of age and ≤ 18 years of age at time of initiation of protocol therapy.
  • Diagnosis: Patients have a histologically or radiographically confirmed relapsed or refractory solid tumor or primary central nervous system (CNS) malignancy.
  • Disease Status: Patients must have radiographically measurable disease.
  • Therapeutic Options: Patients must have relapsed or refractory cancers for which there is no known curative option or other available therapy proven to prolong survival with an acceptable quality of life.
  • Performance Level: Karnofsky ≥ 50% for patients older than 16 years old, and Lansky ≥ 50 for patients 1-16 years old.
  • Prior Therapy: Patients may have received prior therapy including vincristine, irinotecan, or temozolomide. Patients may not have previously been treated with combination therapy of irinotecan and temozolomide.
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  • Patients must be fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of starting protocol therapy, or a minimum of six weeks must have elapsed since prior nitrosurea chemotherapy.
  • Hematopoietic growth factor: At least 7 days must have elapsed since the last administration of filgrastim, or 14 days since administration of pegfilgrastim.
  • Biologic (anti-neoplastic agent): At least 7 must have elapsed since the last administration of any biologic agent.
  • Radiation therapy (XRT): At least 14 days since the last dose of local palliative radiation therapy. Greater than 6 months must have elapsed since the last day of treatment if given total body irradiation, craniospinal irradiation.
  • Autologous or Allogenic Stem Cell Transplant: Complete resolution of graft versus host disease and no current need for immunosuppressive medication. Greater than 3 months must have elapsed since engraftment and no longer requiring transfusion of platelets or injection of colony stimulating factors.
  • Organ Function Requirements
  • Bone Marrow Function: Peripheral absolute neutrophil count (ANC) ≥ 1000/μL; Platelet count ≥ 100,000/μL (no platelet transfusion within 7 days prior to obtaining laboratory result); Hemoglobin ≥ 8.0 gm/dL
  • Adequate Renal Function: Creatinine clearance or glomerular filtration rate ≥ 70ml/min/1.73m^2
  • Adequate Liver Function: Total bilirubin ≤ 1.5x upper limit of normal (ULN) for age; alanine transaminase (ALT) ≤ 5x ULN; Serum albumin ≥ 2gm/dL
  • Informed Consent: All patients ≥ 18 years of age must sign a written informed consent. For patients < 18 years old, the patient's parents or legal guardians must sign a written informed consent, unless the patient is an emancipated minor. Childhood Assent, when age appropriate as per institutional guidelines, should be signed by the participating patient.

Who cannot join

  • Significant organ dysfunction, not meeting inclusion criteria.
  • Pregnancy or Breast-Feeding woman will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
  • Concomitant Medications:
  • Growth factor: Growth factors that support platelet or white cell number of function must not have been administered within the past 7 days.
  • Steroids: Patients with CNS tumors who have not been on a stable or decreasing dose of dexamethasone for the past 7 days.
  • Investigational Drugs: Patients who are currently receiving another investigational drug.
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  • Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents.
  • Medication Allergy: Allergy or intolerance to agents on this protocol: vincristine, irinotecan, temozolomide, or metformin; Allergy to cephalosporins.
  • Infection: Patients who have uncontrolled infection, positive blood cultures within the past 48 hours, or receiving treatment for Clostridium difficile infection.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Florida

    Gainesville, Florida, 32611

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • University of Kentucky

    Lexington, Kentucky, 40536

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Primary Children's Medical Center/Utah

    Salt Lake City, Utah, 84113

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Tampa General Hospital

    Tampa, Florida, 33606

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • The Children's Hospital at Montefiore

    The Bronx, New York, 10467

  • Nemours/Alfred I. duPont Hospital for Children, Delaware

    Wilmington, Delaware, 19803

Other trials in United States

About this study

Official title: A Phase I Trial of Dose Escalation of Metformin in Combination With Vincristine, Irinotecan, and Temozolomide in Children With Relapsed or Refractory Solid Tumors

The purpose of this study is to evaluate the tolerability and safety of escalating doses of metformin on a backbone of vincristine, irinotecan and temozolomide (VIT) in children with recurrent and refractory solid tumors.

Read the detailed description

Metformin is an oral anti-diabetes medication that activates AMP-activated protein kinase (AMPK). Recent data from in vitro and in vivo experiments, as well as epidemiologic retrospective analyses, suggest that metformin has anti-cancer activity. Vincristine, irinotecan, and temozolomide (VIT) is a combination of chemotherapeutic agents that have different mechanisms of action as well as disparate side effect profiles. Two recent phase 1 trials have demonstrated that this regimen is safe and well-tolerated in children with relapsed and refractory solid tumors.

Keywords
central nervous system (CNS), malignancy, relapsed, refractory, pediatric, recurrent
Medical subject headings
Brain Neoplasms, Neoplasms, Recurrence

What participants receive

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

  • VincristineDrug

    Also called VCR, Oncovin, NSC #067574, Vincristine sulfate

    Vincristine (VCR) = 1.5 mg/m^2/day (maximum dose 2 mg), days 1 and 8, administered as intravenous (IV) bolus over 1-5 minutes

  • IrinotecanDrug

    Also called CPT-11, Camptothecin-11, Camptosar ®, NSC#616348

    Irinotecan (IRN) = 50 mg/m^2/day, days 1-5, IV over 60 minutes

  • TemozolomideDrug

    Also called Temodar™, NSC #362856, TEM

    Temozolomide (TEM) = 50 mg/m^2/day by mouth (PO) Days 1-5

  • MetforminDrug

    Also called Glucophage ®, MET

    Metformin (MET) = dose as per dose escalation, divided twice a day (BID), PO continuously for the 21 day cycle.

Study groups in NCT01528046
Study groupRoleWhat they receive
Metformin in Combination with VITExperimentalParticipants will receive metformin in combination with vincristine, irinotecan and temozolomide (VIT).
Receives: Drug: Vincristine; Drug: Irinotecan; Drug: Temozolomide; Drug: Metformin

What is being measured

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

  1. Maximum Tolerated Dose (MTD)

    To determine the maximum tolerated dose (MTD) of metformin when given in conjunction with VIT in children with refractory and relapsed solid tumors.

    Measured: Average of 3 Months

Secondary outcomes (4)

  1. Number of Participants with Antitumor Activity

    To evaluate the antitumor activity of the addition of metformin to VIT.

    Measured: Average of 3 Months

  2. Pharmacokinetics

    To describe the pharmacokinetics of metformin in children with relapsed malignancies receiving VIT combination chemotherapy.

    Measured: Average of 3 Months

  3. Pharmacodynamics

    To define the pharmacodynamics of metformin.

    Measured: Average of 3 Months

  4. Metformin Concentrations

    To determine tissue and tumor metformin concentrations in patients undergoing resection.

    Measured: Average of 3 Months

Timeline

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

  1. First posted7 Feb 2012 (estimated)
  2. Study start24 Sep 2012
  3. Primary completion26 Sep 2019
  4. Study completion3 Feb 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
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01528046
Sponsor's protocol ID
MCC-16962
Other IDs
SP003
Status last verified
Jan 2023
First submitted
3 Feb 2012
Last updated
13 Jan 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Metts JL, Trucco M, Weiser DA, Thompson P, Sandler E, Smith T, Crimella J, Sansil S, Thapa R, Fridley BL, Llosa N, Badgett T, Gorlick R, Reed D, Gill J. A phase I trial of metformin in combination with vincristine, irinotecan, and temozolomide in children with relapsed or refractory solid and central nervous system tumors: A report from the national pediatric cancer foundation. Cancer Med. 2023 Feb;12(4):4270-4281. doi: 10.1002/cam4.5297. Epub 2022 Sep 23.

    PubMed 36151773

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vincristine, Irinotecan and Temozolomide in people with Solid Tumors and Primary Brain Tumors, run by H. Lee Moffitt Cancer Center and Research Institute at 14 sites 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 17 inclusion and 9 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 13 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites 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) (time frame: Average of 3 Months). 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 NCT01528046, 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 13 Jan 2023.

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