Overview

Phase 2 Study of IDH305 in Low Grade Gliomas

Status:
Withdrawn
Trial end date:
2019-01-01
Target enrollment:
0
Participant gender:
All
Summary
Cohort A - neoadjuvant administration of IDH305 at 550 mg BID for 6 weeks followed by surgical resection at 6 weeks. If there is no evidence of progressive disease at 6 weeks (clinical, radiographic or histopathologic exam), the patient will continue on IDH305 at 550 mg BID post-operatively for a maximum of 11 additional 28 day cycles. Subsequent assessment of disease will occur every 2 months starting in Cycle 2. Cohort B - patients who have inoperable tumors but measurable 2HG pre-treatment will be treated with IDH305 at 550 mg BID x 6 weeks. If there is adequate sustained knockdown of 2HG on MRS and disease is stable or improved, then the patient will continue on treatment for a maximum of 11 additional 28 day cycles.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Texas Southwestern Medical Center
Criteria
Inclusion Criteria:

1. Written informed consent prior to any screening procedures that are not part of
standard of care.

2. Age greater than or equal to 18 years.

3. Male or female of any racial or ethnic origin.

4. Measurable 2HG by MR Spectroscopy (above threshold of 1mM, established at UTSW).

5. Karnofsky Performance Status > 70%.

6. Measurable disease per RANO criteria.

7. Female subjects with reproductive potential must have a negative serum pregnancy test
within 7 days prior to start of therapy. Subjects with reproductive potential are
defined as one who is biologically capable of becoming pregnant. Women of childbearing
potential as well as fertile men and their partners must agree to abstain from sexual
intercourse or to use two effective forms of contraception during the study and for 30
days (females and males) following the last dose of IDH305.

Exclusion Criteria:

1. 2HG by MR Spectroscopy below 1 mM.

2. Patients who are currently receiving treatment with a prohibited medication or herbal
remedy that cannot be discontinued at least one week prior to the start of treatment.

3. Narrow therapeutic index substrates of CYP3A, CYP2C9, CYP2C19, and CYP2C8.

4. Medications, herbs and supplements that are strong inhibitors and strong inducers of
CYP3A.

5. Other herbal preparations and supplements.

6. Inhibitors of UGT1A1.

7. Patients who have out of range laboratory values defined as:

- Absolute neutrophil count (ANC) <1.0 x 109/L

- Hemoglobin (Hgb) <8 g/dL

- Platelets <75 x 109/L

- Total bilirubin > ULN

- AST or ALT >3 x ULN

- Serum creatinine >1.5 x ULN

8. Karnofsky Performance Status < 70%.

9. Malignant disease other than that being treated in this study. Exceptions to this
exclusion include the following: malignancies that were treated curatively and have
not recurred within the prior 2 years; completely resected basal cell and squamous
cell skin cancers; any malignancy considered to be indolent and that has never
required therapy; and completely resected carcinoma in situ of any type.

10. Patients with corrected QT using the Fridericia correction (QTcF) > 470 msec, or other
clinically significant, uncontrolled heart disease, including acute myocardial
infarction or unstable angina < 3 months prior to the first dose of IDH305.

11. Any other medical condition that would, in the investigator's judgment, prevent the
patient's participation in the clinical study due to safety concerns or compliance
with clinical study procedures such as the presence of other clinically significant
cardiac, respiratory, gastrointestinal, renal, hepatic or neurological disease.

12. Patients with Gilbert's syndrome or other heritable diseases of bile processing.

13. Patients who are claustrophobic or who have other contraindications to MRI, such as an
implanted pacemaker device, vascular clips, prosthetic valves, or otologic implants.

14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

15. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 30 days after the use of the investigational medication. Highly
effective contraception methods include:

- Total abstinence (when this is in line with the preferred and usual lifestyle of
the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception.

- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
taking study treatment. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment Male
sterilization (at least 6 months prior to screening). The vasectomized male
partner should be the sole partner for that patient.

- Combination of any two of the following (a+b, a+c, or b+c):

a. Use of oral, injected or implanted hormonal methods of contraception or other
forms of hormonal, for example hormone vaginal ring or transdermal hormone
contraception.

- In case of use of oral contraception women should have been stable on the same
pill for a minimum of 3 months before taking study treatment.

b. Placement of an intrauterine device (IUD) or intrauterine system (IUS). c.
Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

16. Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at
least six weeks ago. In the case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment is she
considered not of child bearing potential.

17. Sexually active males must use a condom during intercourse while taking the drug and
for 30 days after stopping treatment and should not father a child in this period. A
condom is required to be used also by vasectomized men as well as during intercourse
with a male partner in order to prevent delivery of the drug via semen.