Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1P/19Q Deleted Anaplastic Glioma: The Catnon Intergroup Trial

Study ID
STU 052013-061

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • UT Southwestern Moncrieff Cancer Center

Contact
Penny Currykosky
214-648-2926
penny.currykosky@utsouthwestern.edu

Principal Investigator
Edward Pan

Summary

This trial is a follow up study of eoRTC 26981 and of eoRTC 26951 addressing the overall strategy of optimizing the treatment in newly diagnosed anaplastic glioma patients without combined 1p/19q loss. Patients will be randomized immediately after surgery to one of the four following therapeutic options:
arm 1 : RT alone (and further treatment including chemotherapy at progression)
arm 2 : RT and concurrent CT
arm 3 : RT + adjuvant CT
arm 4 : RT and concurrent CT + adjuvant CT

Twelve months of adjuvant treatment is foreseen. Patients will be included based on the 1p/19q status of the tumor. Centers with known expertise in 1p/19q testing will be allowed to include patients based on local testing,
with central review for 1p/19q testing (and histology). For sites without access to 1p/19q testing a central facility will be created. Methylation status of the MGMT promoter gene will be a stratification factor.

Participant Eligibility

All patients are initially registered into the trial as soon as possible after surgery. After this point,
material must be sent for 1p/19q analysis and MGMT promoter methylation assay. This should
again be done as soon as possible. Patients can only be randomized into the trial within 8 days from the start of radiotherapy; at this time, all baseline requirements for the study must have been
fulfilled.
1. Histologically confirmed newly diagnosed anaplastic oligodendroglioma, anaplastic
oligoastrocytoma or anaplastic astrocytoma by local diagnosis
2. Availability of tumor material for central 1p/19q assessment, central MGMT promoter methylation assessment and central pathology review.
3. Previous surgery for a low grade tumor is allowed, provided histological confirmation of an anaplastic tumor is present at the time of progression
4. WHO performance status 0-2
5. Age >= 18 years
6. All patients must use effective contraception if of reproductive potential. Females must not be
pregnant or breast feeding
7. Absence of known HIV infection, chronic hepatitis B or hepatitis C infection
8. Absence of any other serious medical condition that can interfere with follow-up
9. Absence of any medical condition which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction)
10. No previous other malignancies, except for any previous malignancy which was treated with
curative intent more than 5 years prior to registration, and except for adequately controlled limited basal cell carcinoma of the skin, squamous carcinoma of the skin or carcinoma in situ of
the cervix.
11. Absence of any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule; those conditions should
be discussed with the patient before registration in the trial
12. No prior chemotherapy (including no treatment with BCNU containing wafers (Gliadel(RegisteredTM))
13. No prior radiotherapy to the brain
14. Before patient registration, written informed consent must be obtained, according to ICH/GCP,
and national/local regulations.

Randomization step - The combination of:
Histologically confirmed newly diagnosed anaplastic oligodendroglioma, anaplastic oligoastrocytoma or anaplastic astrocytoma by local diagnosis
AND
Absence of combined 1p/19q loss both of which must have been determined by either local testing or central review
1. Availability of tumor material for central 1p/19q assessment, central MGMT promoter methylation assessment and central pathology review
2. WHO performance status 0-2
3. Age >= 18 years
4. Previous surgery for a low grade tumor is allowed, provided histological confirmation of an
anaplastic tumor is present at the time of progression
5. Start of radiotherapy within 8 days from randomization
6. Start of radiotherapy within 7 weeks (49 days) from surgery (extra 2 days could be allowed)
7. Patients must be on a stable or decreasing dose of steroids for at least two weeks
8. No prior chemotherapy (including no treatment with BCNU containing wafers (Gliadel(RegisteredTM))
9. No prior radiotherapy to the brain
10. No concomitant treatment with other anti-cancer agents or with any other experimental agent
11. Adequate hematological, renal and hepatic function according to all of the following laboratory
values (to be performed within 28 days prior to randomization):
a.) neutrophils greater or equal to 1.5*109 cells/l
b.) platelets greater or equal to 100*109 cells/l
c.) bilirubin < 1.5 times upper limit of laboratory normal
d.) alkaline phosphatase, ASAT and ALAT <2.5 times upper limit of laboratory normal
e.) serum creatinine lower than 1.5 times upper limit of laboratory normal
12. All patients must use effective contraception if of reproductive potential. Females must not be
pregnant or breast feeding
13. Absence of known HIV infection, chronic hepatitis B or hepatitis C infection
14. Absence of any other serious medical condition that could interfere with follow-up
15. Absence of any medical condition which could interfere with oral medication intake (e.g.,
frequent vomiting, partial bowel obstruction)
16. Absence of any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule.
17. Before patient randomization, written informed consent must be given according to ICH/GCP,
and national/local regulations.
18. Patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry are acceptable.