Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 750 for:    Phase II astrocytoma

Phase I/II Trial of Safety and Anti-tumor Efficacy of AXL1717(Picropodophyllin) in the Treatment of Recurrent Malignant Astrocytomas (AXL1717)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01721577
Recruitment Status : Unknown
Verified January 2015 by Robert Aiken, M.D., Rush University Medical Center.
Recruitment status was:  Recruiting
First Posted : November 4, 2012
Last Update Posted : January 12, 2015
Sponsor:
Collaborator:
Axelar AB
Information provided by (Responsible Party):
Robert Aiken, M.D., Rush University Medical Center

Tracking Information
First Submitted Date  ICMJE October 29, 2012
First Posted Date  ICMJE November 4, 2012
Last Update Posted Date January 12, 2015
Study Start Date  ICMJE December 2012
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2015)
  • Phase I - Determine recommended Phase II dose. [ Time Frame: 8 months ]
    To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas
  • Phase II - Determine Antitumor effect [ Time Frame: 4 months ]
    To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating progression-free-survival (PFS) at 6-months.
Original Primary Outcome Measures  ICMJE
 (submitted: November 1, 2012)
  • Phase I - Determine recommended Phase II dose. [ Time Frame: 8 months ]
    To determine the recommended phase II dose (RPTD) of AXL1717 in recurrent malignant astrocytomas
  • Phase II - Determine Antitumor effect [ Time Frame: 4 months ]
    To determine if AXL1717 has any antitumor effect as a single agent treatment in recurrent malignant astrocytomas by evaluating progression-free-survival (PFS) at 6-months.
  • Phase I - Safety and tolerability [ Time Frame: 6 months ]
    • physical/neurological examinations (pathological findings and quality and quantity)
    • adverse events (quality and quantity per dose level)
    • vital signs, ECG, laboratory parameters (pathological findings as quality and quantity, for laboratory parameters, descriptive statistics)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2012)
  • Phase I - Maximum Tolerated Dose (MTD) [ Time Frame: 8 months ]
    To identify the MTD of AXL1717.
  • Phase I - Molecular markers of optimum response [ Time Frame: 8 months ]
    To assess potential molecular markers that might predict optimum response sub-population groups
  • Phase I - Molecular Markers of IGF (insulin like growth factor)-1R pathway [ Time Frame: 8 months ]
    To evaluate surrogate molecular markers of IGF-1R pathway activation/inhibition after treatment with AXL1717 in patients with malignant astrocytomas
  • Phase II - Time-To-Progression (TTP) and Overall Survival (OS) [ Time Frame: 4 months ]
    To determine time-to-progression (TTP) and overall survival (OS) of patients treated with AXL1717
  • Phase II - Overall Response Rate [ Time Frame: 4 months ]
    To assess overall response rate (ORR) in recurrent malignant astrocytomas after treatment with AXL1717
  • Phase II - Imaging Evidence of Response. [ Time Frame: 4 months ]
    To identify surrogate imaging evidence of response on MRI (magnetic resonance imaging)sequences by RANO criteria (with additional special attention to T2-FLAIR, DWI (diffusion-weighted imaging), perfusion MRI and multi-voxel MRS (magnetic resonance spectroscopy) sequences).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/II Trial of Safety and Anti-tumor Efficacy of AXL1717(Picropodophyllin) in the Treatment of Recurrent Malignant Astrocytomas
Official Title  ICMJE Phase I/II Clinical Trial of the Safety, Tolerability, and Anti-tumor Efficacy of the IGF-1R Inhibitor, AXL1717 (Picropodophyllin), in the Treatment of Recurrent Malignant Astrocytomas
Brief Summary This is a single-center, open-label, non-randomized, Phase I/IIa study to investigate the safety, tolerability, and antitumor efficacy of AXL1717 (picropodophyllin as active agent formulated in an oral suspension; PPP) in patients with recurrent malignant astrocytomas (glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma). Patients will be treated for up to 5 cycles. A treatment cycle is defined as 28 days+7 days rest (28+7 days during cycle 1 to 4, and 28 days during cycle 5). The following cycle will not be started until the treatment continuation criteria are fulfilled. Concomitant supportive therapies will be allowed.
Detailed Description

AXL1717, as a ready-to-use suspension of picropodophyllin for oral administration, will be distributed in bottles for single use at a concentration of 25 mg/mL. Fixed doses will be used, i.e. there are no adjustments for weight or body surface. There will be no randomization or blinding in the study.

The trial will be divided in two phases. In the first phase, 10-20 patients will be enrolled and treated with 300-520 mg BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 in patients with recurrent or progressive glioblastoma and to assess the safety and toxicity of AXL1717 in this patient population. The study has a 3+3 design and the first cohort will be treated with 400 mg AXL1717 BID for 28 days repeated in up to 5 cycles. If dose-limiting toxicity (DLT) such as neutropenia occurs, dosing will be interrupted and the individual patient will, following normalization, be restarted on the same or a lower dose level according to standardized procedure. If two or three of the first 3 patients on a specific dose level experience a DLT during the first 28 days of treatment with AXL1717, the following patients will be treated with a lower dose level. If one DLT occurs during the first 28 days of dosing in the first 3 three patients another 3 patients will be treated with the same dose level. If 2 of the 6 patients display DLT, the next patients will be treated with a lower dose level. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RPTD. All assessments with respect to dose adjustments for subsequent cohorts will be done during the first 28 days of treatment. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).

In the second phase, 12 patients will be enrolled and treated with the identified RP2D of AXL1717 for 28 days repeated in five cycles. The primary endpoints of phase II is to assess the proportion of patients who are progression-free at 24 weeks and to assess safety, tolerability, and adverse event profile of AXL1717.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Gliosarcoma
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligoastrocytoma
  • Anaplastic Ependymoma
Intervention  ICMJE Drug: AXL1717
IGF-1 receptor inhibitor
Other Name: picropodophyllin
Study Arms  ICMJE Experimental: AXL1717
In the first phase, 10-20 patients will be enrolled and treated with 300-520 mg BID of AXL1717 for 28 days. The primary endpoint of the first phase is to determine the recommended Phase 2 dose (RP2D) of AXL1717 and to assess the safety and toxicity of AXL1717. The study has a 3+3 design and the first cohort will be treated with 400 mg AXL1717 BID for 28 days repeated in up to 5 cycles. The highest dose level without DLT or with maximally one DLT out of 6 patients will be the RP2D. Non-progressing patients may be treated for a total of five 28-day cycles (24 weeks).
Intervention: Drug: AXL1717
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: November 1, 2012)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2015
Estimated Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  1. Be informed of the nature of the study and have provided written informed consent
  2. At least 18 years of age
  3. ECOG performance of 0, 1, or 2, or KPS (Karnofsky performance status) ≥ 60.
  4. Pathological verification of a WHO grade 4 astrocytoma (glioblastoma or gliosarcoma), or WHO Grade 3 anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic ependymoma.
  5. Documented recurrent glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, or anaplastic ependymoma after at least one failed treatment of chemotherapy and radiation
  6. Expected survival of at least 3 months
  7. At least 2-weeks from cytoreductive surgery, if performed, 4-weeks from bevacizumab or other chemotherapy (6-weeks if prior chemotherapy was nitrosourea) and 12-weeks from completion of radiotherapy.
  8. Ability to undergo MRI scanning without and with imaging dye on a periodic basis as defined in the protocol
  9. Preserved major organ functions, i.e: Blood leukocyte count ≥ 3.0 x 109/L Blood absolute neutrophil count ≥ 1.5 x 109/L Blood platelet count ≥ 100 x109/L Blood hemoglobin ≥ 100 g/L (transfusions are allowed) Plasma total bilirubin level ≤ 1.5 times the upper institutional limit (ULN) of the ‖normal‖ (i.e. reference) range Plasma AST (aspartate aminotransferase) or ALT ≤ 2.5 times upper institutional limit (ULN) of the ‖normal‖ range Plasma creatinine ≤ 1.5 times upper institutional limit (ULN) of the ‖normal‖ range 12-lead ECG with normal tracings; or changes that are not clinically significant and do not require medical intervention, and QTc < 500 ms At least seven (7) days off of medications which inhibit or induce CYP2C9 or CYP3A4 before first study treatment day

Exclusion criteria

  1. Any or other major recent or ongoing disease that, according to the Investigator, poses an unacceptable risk to the patient
  2. Grade 3 or higher constipation within the past 28 days or grade 2 constipation within the past 14 days before randomization. (Patients with grade 2 constipation within the past 14 days could be re-screened if constipation decreases to ≤ grade 1 with optimal management of constipation.)
  3. Coexisting uncontrolled medical condition.
  4. Hepatitis B or Hepatitis C, or HIV infection requiring anti-retroviral therapy
  5. Active malignancy other than basal cell skin cancer
  6. Other active malignancy during the previous 3 years
  7. Major surgical procedure within 4 weeks
  8. Prior stereotactic or gamma knife radiosurgery or proton radiation, unless unequivocal progression by functional neuro-imaging (PET, dynamic MRI, MRS, SPECT) or by re-operation with documented histologic confirmation of recurrence.
  9. Prior anti-tumor therapy, as follows: at least 12-weeks from radiation therapy; at least 4-weeks from prior treatment with temozolomide or bevacizumab, 6-weeks from BCNU or CCNU.
  10. Women of child bearing potential (WOCBP) who do not consent to using acceptable methods of birth control (oral contraceptives, IUD). For purposes of this study, WOCBP include any female who has experienced menarche, who has not undergone tubal ligation, and who is not postmenopausal.
  11. Medically uncontrolled Type 1 or Type 2 diabetes mellitus
  12. Pregnancy or lactation
  13. Current participation in any other investigational clinical trial within 4-weeks.
  14. Eastern Cooperative Oncology Group (ECOG) performance status > 2 after optimization of medications (See Appendix 4) or KPS < 60
  15. Anticipated Life expectancy less than 3 months
  16. Contraindications to the investigational product or known or suspected hypersensitivity
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01721577
Other Study ID Numbers  ICMJE 11090804
VABC; GCR ( Other Grant/Funding Number: Voices Against Brain Cancer; Gateway for Cancer Research )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Robert Aiken, M.D., Rush University Medical Center
Study Sponsor  ICMJE Rush University Medical Center
Collaborators  ICMJE Axelar AB
Investigators  ICMJE
Principal Investigator: Robert Aiken, MD Rush University Medical Center
PRS Account Rush University Medical Center
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP