PAZIT Study for Children and Young Adults With Relapsed or Refractory Sarcoma

Completed · Phase 1

Conditions studied: Sarcoma, Refractory Sarcoma

In brief

This is the first study to evaluate the safety and clinical activity of the combination of oral pazopanib, intravenous or oral irinotecan, and oral temozolomide in pediatric and young adult patients with relapsed or refractory sarcomas. This study will use a 3 + 3 design for dose escalation (Part 1), followed by an expansion cohort (Part 2) at the recommended phase 2 dose level.

Key facts

Study ID

NCT03139331

Run by

University of California, San Francisco

People needed

16

Starts

2017-06-06

Expected to finish

2020-09-30

Last updated by the study team

2021-01-05

Who can join

Age: 6 and older, up to 30. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age: Patients must be 6-30 years of age at the time of study enrollment.
• Body Surface Area: Eligible patients have a body surface area >/= 0.7 m2 AND be able to swallow whole tablets at the time of study enrollment.
• Diagnosis: Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at time of relapse.
• Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)
• Osteosarcoma
• Rhabdomyosarcoma
• Non-rhabdomyosarcoma soft tissue sarcoma
• Desmoplastic small round cell tumor
• Note: Patients with known involvement of the central nervous system (CNS) by malignancy will be included if there is no evidence of active bleeding or intratumoral hemorrhage on radiographic imaging.
• Disease Status: Patients must have either measurable or evaluable disease
• Therapeutic Options: Patient's current disease state must be one for which there is not known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
• Performance Level: Karnofsky >/= 50% for patients > 16 years of age and Lansky >/= 50% for patients </= 16 years of age.
• Note: Neurologic deficits in patients with metastatic CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
• Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
• Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Biologic (anti-neoplastic agent): At least 7 days must have passed after the last treatment with a biologic agent. For agents that have known adverse events occurring beyond 7 days from administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
• Monoclonal 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.
• External beam radiation therapy (XRT): >/= 2 weeks must have elapsed for local palliative XRT (small port) and enrollment on study. At least 24 weeks must have elapsed since prior Total Body Irradiation (TBI), radiation to ≥50% of pelvis, or craniospinal radiation; >/= 6 weeks must have elapsed if the patient has received other substantial bone marrow radiation.
• Stem Cell Transplant (SCT): No evidence of active graft-versus-host disease (GVHD) and >/= 2 months must have elapsed since transplant or rescue.
• Prior treatment with pazopanib, irinotecan, temozolomide: Patients may not have previously received pazopanib. However, patients may have received other vascular endothelial growth factor (VEGF) blocking tyrosine kinase inhibitors. Patients must have recovered from any VEGF blocking drug-related toxicity (e.g., proteinuria).
• Patients previously treated with irinotecan and/or temozolomide will be eligible for this study provided they did not progress while receiving one of these agents.
• Organ Function Requirements:
• Adequate Bone Marrow Function defined as:

You may not qualify if…

• Pregnancy or Breast-Feeding: Pregnant or breastfeeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Negative pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. The definition of adequate contraception will be based on the judgment of the principal investigator or designated associate. Study drug may also potentially be secreted in milk and therefore breastfeeding women are excluded.
• Concomitant Medications:
• Corticosteroids: Patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible.
• Investigational Drugs: patients who are currently receiving another investigational drug are not eligible.
• Anti-cancer Agents or Radiation Therapy: Patients who are currently receiving other anti-cancer agents or radiation therapy are not eligible.
• Anti-hypertensive Medications: Patients who are currently receiving more than one anti-hypertensive medication or whose blood pressure is not controlled as defined by protocol are not eligible for study enrollment.
• Anti-coagulation: Patients must not be on therapeutic anti-coagulation. Prophylactic anti-coagulation (i.e., intraluminal heparin) of venous or arterial access devices is allowed.
• Anti-inflammatory and Anti-platelet Agents: Patients currently receiving aspirin, and/or ibuprofen, or other NSAIDs are not eligible.
• Enzyme-inducing Anti-convulsants: Patients who are currently receiving enzyme-inducing anti-convulsants are not eligible.
• CYP3A4 Substrates and Drugs Causing QTc Prolongation: Patients receiving drugs with a known risk of torsades de pointes are not eligible. A list of enzyme inducing, enzyme inhibiting, and other prohibited drugs is provided by the protocol.
• Note: This list includes the prohibition of grapefruit for 14 days prior to enrollment.
• Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 4 weeks prior to study enrollment.
• Patients who are unable to swallow whole tablets are not eligible.
• Infection: Patients who have an active or uncontrolled infection are not eligible.
• Bleeding and Thrombosis: Patients will be excluded if any of the following are present:
• Evidence of active bleeding, intratumoral hemorrhage, or bleeding diathesis.
• History (within 6 months prior to study enrollment) of pulmonary embolism, deep vein thrombosis (DVT), or other venous thromboembolic event.
• History of hemoptysis within 6 weeks prior to study enrollment.
• Patients with known involvement of the CNS by malignancy will be included if there is no evidence of active bleeding or intratumoral hemorrhage on radiographic imaging.
• Surgery: Patients who have had or are planning to have the following invasive procedures will be excluded:
• Major surgical procedures, laparoscopic procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 therapy. Subcutaneous port placement or central line placement is not considered major surgery, but must be placed greater than 48 hours from planned Day 1 of therapy.
• Core biopsy within 7 days prior to Day 1 therapy.
• Fine needle aspirate or central line placement within 48 hours prior to Day 1 therapy.
• Note: Routine bone marrow aspirate and biopsy for the purposes of disease staging are not part of these exclusion guidelines.
• Patients with serious or non-healing wound, ulcer, or bone fracture.

Where it is running

• UCSF Benioff Children's Hospital, Oakland — Oakland, California, United States
• University of California, San Francisco — San Francisco, California, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.