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NCT Number: NCT01331135

Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

The best treatment for recurrent cancers or those that do not respond to therapies is not known. Typically, patients with these cancers receive a combination of cancer drugs (chemotherapy), surgery, or radiation therapy. These treatments can prolong their life but may not offer a long-term cure.

This study proposes using a drug called Sirolimus in combination with common chemotherapy drugs to treat patients with recurrent and refractory solid tumors. Sirolimus has been found to inhibit cell growth and to have anti-tumor activity in pediatric solid tumors in previous studies and, therefore, has the potential to increase the effectiveness of the chemotherapy drugs when given together.

This study wil investigate the highest dose of Sirolimus that can be given orally with other oral chemotherapy drugs. Cohorts of 2 subjects will be started at the minimum dose. The dose will be increased in the next 2 subjects as long as there were no major reactions in the previous groups. This study will also seek to learn more about the side effects of sirolimus when used in this combination and what effects the drug has on the white cells and the immune system. Successful use of this drug will impact the cancer population greatly by providing an increased chance of survival to those with resistant or recurrent cancers.

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Key information

Conditions

Ewing's Sarcoma Adenocarcinoma Astrocytoma Atypical Teratoid/Rhabdoid Tumor Carcinoma Carcinoma, Renal Cell Clear Cell Sarcoma Congenital, Hereditary, and Neonatal Diseases and Abnormalities Disease Attributes Ependymoma Eye Diseases Eye Diseases, Hereditary Eye Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Germ Cell Tumor Glioma Hepatoblastoma Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Medulloblastoma Myosarcoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Bone Tissue Neoplasms, Complex and Mixed Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Muscle Tissue Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplastic Syndromes, Hereditary Neuroblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Neuroectodermal Tumors, Primitive, Peripheral Osteosarcoma Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Renal Cell Carcinoma Retinal Diseases Retinal Neoplasms Retinoblastoma Rhabdoid Tumor Rhabdomyosarcoma Sarcoma Sarcoma, Clear Cell Sarcoma, Ewing Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Wilms Tumor

Age range

Up to 30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

About this study

Sirolimus, is a potent immunosuppressive drug that is approved for use in prevention against allograft rejection following solid organ transplant. It has anti-tumor effects mainly by blocking signals which drive cells from G1 to S phase during cell cycle through inhibition of mTOR, thus inhibiting cell growth. Sirolimus, as well as other mTOR inhibitors, has shown anti-tumor activity in pediatric solid tumor xenografts. Children with relapsed and/or refractory solid tumors are in need of novel therapeutic approaches. One option for these patients is the use of prolonged exposure to low dose antiangiogenic chemotherapy, with agents such as etoposide and cyclophosphamide. In this phase I trial the feasibility and optimal dosing for daily sirolimus, in combination with daily celecoxib, and low dose etoposide alternating with cyclophosphamide, will be determined in children with relapsed and refractory solid tumors. p70S6 kinase inhibition will be used as a surrogate for mTOR inhibition. The potential immunosuppressive effect of sirolimus administered on this schedule will be assessed by serial lymphocyte subsets and assessment of memory T cell number.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • must be <=30 years of age at time of study enrollment
  • histologic verification of malignancy at original diagnosis or relapsis except in patients with intrinsic brain stem tumors, optic pathway gliomas or patients wtih pineal tumors and evaluations of serum or CSF alpha-fetoprotein or beta-HCG
  • measurable or evaluable disease
  • disease state must be one for which there is no known curative therapy
  • Performance level >=50%
  • Patients must have fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy
  • no evidence of acute graft vs. host disease and >=3 months since transplant
  • organ function as defined in eligibility section of protocol

Exclusion criteria

  • patients cannot be pregnant or breast-feeding
  • patients must agree to use of an effective contraceptive method
  • no growth factors that support platelet or white cell number or function for at least 7 days prior to enrollment
  • patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible
  • patients receiving any other investigational drugs
  • patients receiving any other anti-cancer drugs
  • patients who have an uncontrolled infection

Treatment and study plan

sirolimus

Drug

daily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2.

Other names: rapamune, cypher, renacept

Primary outcomes

  1. Maximum tolerated dose (MTD)

    Time frame: 2 years after treatment starts

    estimate the maximum tolerated dose (MTD) and recommended Phase II dose of sirolimus administered orally once daily for 42 days in combination with metronomic chemotherapy in children with recurrent or refractory solid tumors.

Secondary outcomes

  1. define and describe toxicities of sirolimus

    Time frame: 2 years post treatment

    To define and describe the toxicities of sirolimus administered in combination with metronomic chemotherapy administered according to this schedule.

  2. anti-tumor activity of sirolimus

    Time frame: 2 years post treatment

    To assess the antitumor activity of sirolimus administered in combination with metronomic chemotherapy to children with recurrent and refractory solid tumors within the confines of a Phase I study.

  3. evaluate correlation of p70S6 kinase activity

    Time frame: 2 years post treatment

    To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.

  4. evaluate risk of infection

    Time frame: 2 years post treatment

    To evaluate the effect of this combination therapy on lymphocyte subsets and memory T-cells, and to correlate that with risk of infection.

Sponsors and collaborators

Lead sponsor

Emory University

Other

Collaborators

  • Children's Healthcare of Atlanta

Registry information

Official study title

Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study

Acronym: Aflac ST0901

Important dates

Study start
2011
Primary completion
2017
Study completion
2017
First posted
Apr 7, 2011
Registry last updated
May 29, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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