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Study of Suberoylanilide Hydroxamic Acid (SAHA) With Temsirolimus in Children With Diffuse Intrinsic Pontine Glioma (DIPG)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2015 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT02420613
First received: April 15, 2015
Last updated: May 14, 2015
Last verified: May 2015
  Purpose

The goal of this clinical research study is to learn the highest tolerable dose of temsirolimus that can be combined with a stable dose of vorinostat and/or radiation therapy and given to patients with DIPG. The safety of this treatment combination will also be studied.


Condition Intervention Phase
Diffuse Intrinsic Pontine Glioma
Drug: Vorinostat
Radiation: Radiation Therapy
Drug: Temsirolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) With Temsirolimus in Children With Newly Diagnosed or Progressive Diffuse Intrinsic Pontine Glioma (DIPG)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Temsirolimus with Vorinostat [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    MTD defined as the highest dose studied in which six patients have been treated and at most two patients with dose-limiting toxicities (DLTs) are observed.


Secondary Outcome Measures:
  • Response Rate of Vorinostat and Temsirolimus [ Time Frame: After 3, 28 day cycles ] [ Designated as safety issue: No ]

    Complete Response (CR) defined as no evidence of disease at primary tumor site. Partial Response (PR) defined as a greater than 50% reduction in the product of greatest tumor diameter and its perpendicular diameter on MRI scan.

    Minor Response (MR) defined as a greater than or equal to 25% but less than or equal to 50% reduction in the product of greatest tumor diameter and its perpendicular diameter on MRI scan.

    Stable Disease (SD) defined as a less than 25% reduction in the product of the greatest tumor diameter and its perpendicular diameter on MRI scan, Progressive Disease (PD) defined as a more than 25% increase in tumor size radiographically or the emergence of new lesions or CSF positivity or evidence of clinical progression.

    Response Evaluation Criteria in Solid Tumors (RECIST) used from the NCI for assessment of radiographic response.



Estimated Enrollment: 18
Study Start Date: August 2015
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Newly Diagnosed DIPG Group

Participants receive radiation therapy with Vorinostat followed by adjuvant therapy with Vorinostat and Temsirolimus for 10 cycles.

Dose Escalation Phase Starting Dose of Vorinostat: 230 mg /m2 by mouth daily. During radiation, participants receive Vorinostat daily from Mon-Friday along with radiation. After radiation therapy, participant rests for 4 weeks in which no radiation therapy or study drug received .

Radiation therapy (RT) administered in single daily fractions of 1.8 Gy for 30 treatments over 6-7 weeks. Total dose of radiation 54 Gy.

Maintenance Phase Starting Dose for Vorinostat: 230 mg/m2/dose by mouth once daily in a 28 day cycle.

Maintenance Phase Starting Dose for Temsirolimus: 25 mg/m2 by vein on Day 1 and Day 8 of a 28 day cycle.

Drug: Vorinostat

Newly Diagnosed DIPG Group:

Dose Escalation Phase Starting Dose of Vorinostat: 230 mg /m2 by mouth daily. During radiation, participants receive Vorinostat daily from Mon-Friday along with radiation. After radiation therapy, participant rests for 4 weeks in which no radiation therapy or study drug received .

Maintenance Phase Starting Dose for Vorinostat: 230 mg/m2/dose by mouth once daily in a 28 day cycle.

Progressive DIPG Group:

Dose Escalation Phase Starting Dose of Vorinostat: at 230 mg/m2 by mouth from Day 1 to Day 8.

Maintenance Phase Starting Dose for Vorinostat: 230 mg/m2/dose by mouth once daily of a 28 day cycle.

Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
Radiation: Radiation Therapy
Radiation therapy (RT) administered in single daily fractions of 1.8 Gy for 30 treatments over 6-7 weeks. Total dose of radiation 54 Gy.
Other Name: XRT
Drug: Temsirolimus

Newly Diagnosed DIPG Group:

Maintenance Phase Starting Dose for Temsirolimus: 25 mg/m2 by vein on Day 1 and Day 8 of a 28 day cycle.

Progressive DIPG Group:

Dose Escalation Phase Starting Dose of Temsirolimus: 25mg/m2 by vein on Day 1 and Day 8.

Maintenance Phase Starting Dose for Temsirolimus: 25 mg/m2 by vein on Day 1 and Day 8 of a 28 day cycle.

Other Names:
  • CCI-779
  • Torisel
Experimental: Progressive DIPG Group

Participants receive 12 cycles of therapy with each cycle being repeated every 28 days.

Dose Escalation Phase Starting Dose of Vorinostat: at 230 mg/m2 by mouth from Day 1 to Day 8.

Dose Escalation Phase Starting Dose of Temsirolimus: 25mg/m2 by vein on Day 1 and Day 8.

Maintenance Phase Starting Dose for Vorinostat: 230 mg/m2/dose by mouth once daily of a 28 day cycle.

Maintenance Phase Starting Dose for Temsirolimus: 25 mg/m2 by vein on Day 1 and Day 8 of a 28 day cycle.

Drug: Vorinostat

Newly Diagnosed DIPG Group:

Dose Escalation Phase Starting Dose of Vorinostat: 230 mg /m2 by mouth daily. During radiation, participants receive Vorinostat daily from Mon-Friday along with radiation. After radiation therapy, participant rests for 4 weeks in which no radiation therapy or study drug received .

Maintenance Phase Starting Dose for Vorinostat: 230 mg/m2/dose by mouth once daily in a 28 day cycle.

Progressive DIPG Group:

Dose Escalation Phase Starting Dose of Vorinostat: at 230 mg/m2 by mouth from Day 1 to Day 8.

Maintenance Phase Starting Dose for Vorinostat: 230 mg/m2/dose by mouth once daily of a 28 day cycle.

Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
Drug: Temsirolimus

Newly Diagnosed DIPG Group:

Maintenance Phase Starting Dose for Temsirolimus: 25 mg/m2 by vein on Day 1 and Day 8 of a 28 day cycle.

Progressive DIPG Group:

Dose Escalation Phase Starting Dose of Temsirolimus: 25mg/m2 by vein on Day 1 and Day 8.

Maintenance Phase Starting Dose for Temsirolimus: 25 mg/m2 by vein on Day 1 and Day 8 of a 28 day cycle.

Other Names:
  • CCI-779
  • Torisel

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   7 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must be > than 6 months and less than or equal to 21 years of age at the time of study enrollment.
  2. Patients with newly diagnosed or progressive DIPG as confirmed by gadolinium enhanced MRI are eligible. MRI must demonstrate that at least 2/3 of the tumor is situated in the pons and that the origin of the tumor is clearly in the pons. Biopsy is not required. Tumors with features not typical of diffuse intrinsic brainstem glioma are not eligible. These include dorsally exophytic brainstem gliomas, cervicomedullary junction tumors, and focal low grade gliomas of the midbrain or brainstem which should undergo resection and pathologic evaluation. Patients, who have received re-irradiation for progression of the tumor, will be eligible if they show evidence of measurable progressive disease after the re-irradiation. Patients at diagnosis with involvement of the spine will not be eligible, however if at progression features of spine involvement are present they will be eligible for Stratum II.
  3. Performance level: At the time of study enrollment patients must have a Karnofsky greater than or equal to 50% for patients > 16 years of age and Lansky greater than or equal to 50 for patients less than or equal to 16 years of age. 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.
  4. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy or radiation to grade 2 or less.
  5. Myelosuppressive chemotherapy: Patients must not have received myelosuppressive therapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
  6. Hematopoietic growth factors: At least 14 days must have passed after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.
  7. Biologic (anti-neoplastic agent): At least 7 days must have elapsed after the last of a biologic agent that is not a monoclonal antibody, to be enrolled on this study.
  8. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
  9. Monoclonal antibodies: At least 3 half-lives must have elapsed after treatment with a monoclonal antibody and enrollment on this study.
  10. Radiotherapy: greater than or equal to 2 weeks must have elapsed for local palliative radiotherapy (re-irradiation for progressive disease or upfront RT at initial diagnosis) and enrollment on study for stratum II. At least 24 weeks must have elapsed if patient received craniospinal radiotherapy due to any other prior malignancies.
  11. Stem Cell Infusion without Total Body Irradiation: The patient must have no evidence of active graft vs. host disease, and greater than or equal to 12 weeks must have elapsed since transplant or stem cell infusion and enrollment on this study for any other pathology.
  12. Prior treatment with vorinostat is allowed but at least 3 weeks must have elapsed from the last dose and effects of prior therapy have resolved.
  13. Concomitant medications: Patients with CNS tumors who are receiving steroids are eligible.
  14. Organ function requirements: Adequate Bone Marrow Function Defined As- Peripheral absolute neutrophil count (ANC) greater than or equal to 1000/microL- Platelet count greater than or equal to 100,000/microL (transfusion independent)- Hemoglobin greater than or equal to 10.0 gm/dL (transfusion independent). Adequate Renal Function Defined As- Serum creatinine less than or equal to 1.5 x institutional upper limit of normal for age. Adequate Liver Function Defined As- Bilirubin (sum of conjugated + unconjugated) less than 1.5 x upper limit of normal (ULN) for age- SGPT (ALT) less than or equal to 110U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.- Serum albumin must be greater than or equal to 2 g/dL.- PT and INR < 1.2 x ULN.
  15. Central Nervous Function Defined As- Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled.
  16. Lipid Function- Serum cholesterol and serum triglyceride levels must be less than 300 mg/dl.
  17. Pregnancy and Contraception- Females > 13 years of age or who have achieved menarche must have a negative pregnancy test within 2 weeks of starting treatment (urine or serum) to be eligible and if sexually active must also agree to use contraception.- Male sexually active patients must agree to use an effective method of contraception.
  18. Therapeutic Options- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  19. Life expectancy: At the time of study enrollment patients must have a life expectancy of greater than or equal to 2 months. Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrollment.

Exclusion Criteria:

  1. Patients with other malignancies will not be eligible for stratum I or II. Patients with disseminated disease including to the spine will not be eligible for stratum 1 but will be eligible for stratum II.
  2. Patients must not have a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, Grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia
  3. Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies
  4. Enzyme-inducing anticonvulsants: Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
  5. Anticoagulants: Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, and others) are not eligible
  6. Angiotensin-converting enzyme (ACE) inhibitors: Patients who are currently receiving ACE inhibitors are not eligible due to the development of angioneurotic edema-type reactions in some subjects who received concurrent treatment with temsirolimus + ACE inhibitors
  7. Anti-GVHD or agents to prevent organ rejection post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial
  8. Patients with history of allergic reactions attributed to compounds of similar chemical; or biologic composition to vorinostat or temsirolimus are not eligible
  9. Infection: Patients who have an uncontrolled infection are not eligible
  10. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
  11. Patients with newly diagnosed DIPG who have received vorinostat previously will not be eligible for stratum I. Patients with progressive DIPG will be eligible if they have received either one of the two drugs vorinostat or temsirolimus but will not be eligible for stratum II if have received both the drugs before
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02420613

Contacts
Contact: Soumen Khatua, MD 713-792-6620

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Soumen Khatua, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02420613     History of Changes
Other Study ID Numbers: 2014-0135
Study First Received: April 15, 2015
Last Updated: May 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Diffuse Intrinsic Pontine Glioma
Vorinostat
Suberoylanilide Hydroxamic Acid
Zolinza
DIPG
Newly Diagnosed
Progressive
Pediatrics
SAHA
MSK-390
Temsirolimus
CCI-779
Torisel
Radiation therapy
XRT

Additional relevant MeSH terms:
Glioma
Vorinostat
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015