Losartan + Sunitinib in Treatment of Osteosarcoma

  • STATUS
    Recruiting
  • End date
    Feb 28, 2025
  • participants needed
    41
  • sponsor
    University of Colorado, Denver
Updated on 28 May 2022
platelet count
renal function
cancer
nitrosoureas
systemic therapy
growth factor
hematopoietic growth factors
kidney function tests
metastasis
neutrophil count
blood transfusion
cancer chemotherapy
pegfilgrastim
myelosuppressive chemotherapy
cellular therapy

Summary

This study is a Phase 1/1b clinical trial that aims to determine the Maximally Tolerated Dose of Losartan and Sunitinib Combination Therapy. Patients will first be accrued to the Dose Escalation phase of the study, using a 3+3 design. Medication dosages will increase until a maximally tolerated dose is found. Patients will then be accrued to the Dose Expansion phase of the trial, where efficacy of pre-determined dose will be preliminarily assessed.

Details
Condition Osteosarcoma
Treatment Sunitinib, losartan
Clinical Study IdentifierNCT03900793
SponsorUniversity of Colorado, Denver
Last Modified on28 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Provision to sign and date the consent form (if individual is a minor, provision of a parent or legal guardian to sign and date the consent form and provision of individual to provide assent for study)
Stated willingness to comply with all study procedures and be available for the duration of the study
Male or female aged 10-40 years old
Histologically confirmed osteosarcoma (at either original diagnosis or relapse) that has either recurred or progressed after at least one prior systemic therapy and for which no curative therapy exists
Patients with surface or periosteal osteosarcoma are not eligible
Patients with active CNS metastasis are not eligible. Previously treated CNS metastases which occurred 3 months or more prior, without evidence of active recurrence, are acceptable
Disease status
Dose Escalation (Part A): Patients must have measurable or evaluable disease
Cohort Expansion (Part B): Patients with measurable or evaluable disease and those with completely resected disease are eligible
Performance status
• ECOG performance status (>18 years old) ≤ 2 or Karnofsky performance score
(<18 years old) > 50\
Prior Therapy
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met (e.g., blood count criteria) the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. At least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): ≥ 7 days after the last dose of agent
Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1
Corticosteroids: ≥ 14 days must have elapsed since last dose of corticosteroid
Hematopoietic growth factors: ≥ 14 days after the last dose of a longacting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor
Interleukins, Interferons and Cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors)
Stem cell Infusions: Autologous stem cell infusion, including boost infusion: ≥ 42 days
Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.)
XRT/External Beam Irradiation including protons: ≥ 14 days after local XRT; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial bone marrow radiation
NOTE: Patients with history of cardiac irradiation with mean cardiac dose > 15 Gy
are not eligible (see exclusion criteria)
Adequate bone marrow function, defined as
Peripheral absolute neutrophil count (ANC) ≥ 750/mm3
Platelet count ≥ 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
Hemoglobin ≥ 8 g/dL (with or without transfusion)
Adequate renal function, defined as
• Creatinine clearance or radioisotope GFR > 70 mL/min/1.73 m2 OR a serum
creatinine based on age/gender as follows
Age 2 to <6: Male=0.8, Female=0.8; Age 6 to <10: Male=1, Female=1; Age 10 to
<13: Male=1.2, Female=1.2; Age 13 to <16: Male=1.5, Female=1.4; Age >/= to 16
Male=1.7, Female=1.4
Adequate hepatic function, defined as
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
SGPT (ALT) ≤ 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
Serum albumin ≥ 2.8 g/dL
Adequate cardiac function, defined as
Current cardiac ejection fraction ≥ 50% by biplane Simpson method on echocardiogram
QTc ≤ 480 ms
Patients with preexisting hyper- or hypothyroidism must be on a stable dose of
medication
Ability to take and retain oral medications. NOTE: Medication can be administered via nasogastric or gastrostomy tube

Exclusion Criteria

Patients who underwent major surgery within 14 days prior to start of treatment are not eligible. NOTE: Core biopsy or central line placement are considered minor and are allowed within any time limitations
Patients with uncontrolled coagulopathy or bleeding disorder, or any active bleeding (i.e. gastrointestinal or pulmonary) deemed to be clinically significant by investigator are not eligible
Patients with history of pulmonary embolism or significant thromboembolic event with the preceding 28 days. Patients with thromboembolic events > 28 days before enrollment who are stable on or completed an anticoagulation course are eligible
Patients with history of cardiac irradiation with mean cardiac dose > 15 Gy are not eligible
Patients with symptomatic cardiac disease (i.e. New York Heart Association or Modified Ross Heart Failure Classification for Children > class 2) are not eligible
Patients with any history of cardiac dysfunction including prior abnormal echocardiogram (ejection fraction < 50%), severe or unstable angina, peripheral vascular disease, congenital prolonged QTc syndrome, clinically significant cardiac arrhythmias, stroke, or myocardial infarction are not eligible
Pregnancy
Pregnant or breast-feeding women will not be entered on this study because there is not yet available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in females who are post-menarchal
Males or females of reproductive potential may not participate unless they have agreed to practice 1 highly effective and 1 additional effective (barrier) method of contraception at the same time during the entire study treatment period and through 3 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. Patients who themselves or their partners have undergone female or male sterilization do not require 2 methods of contraception. Highly effective methods are defined as those with <1% failure rate with perfect use and include: oral contraceptive pills (combined or progesterone only), intrauterine devices (IUD), hormonal implant or injection, contraceptive patch, and vaginal ring
Concomitant medications
Anti-hypertensives: Patients requiring more than one antihypertensive medication to control blood pressure, or have baseline blood pressure > 95th percentile for age are not eligible (see Appendix VIII)
Corticosteroids: Patients receiving systemic corticosteroids are not eligible. > 14 days must have elapsed since last systemic corticosteroid. Note: patients using topical or inhaled corticosteroids are eligible
Investigational Drugs: Patients currently receiving another investigational drug are not eligible
Anti-cancer agents: Patients currently receiving other anti-cancer agents are not eligible
Drug interactions: Patients who require treatment with medications that are strong inhibitors or inducers of CYP3A4 or inhibitors of CYP2A9 or have received these medications in the 7 days prior to enrollment, are not eligible. Patients who require treatment with enzyme inducing anticonvulsants are not eligible (see Appendix III)
Medications that prolong QTc: Patients who require treatment with medications known to prolong QTc are not eligible
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note