RTOG 98-02
A PHASE II STUDY OF OBSERVATION IN FAVORABLE LOW-GRADE GLIOMA AND PHASE III STUDY OF RADIATION WITH OR WITHOUT PCV CHEMOTHERAPY IN UNFAVORABLE LOW-GRADE GLIOMA
| ECOG (R9802) Radiation Oncology Minesh Mehta, M.D. (608) 263-8500 FAX (608) 263-9167 |
Study Chairs RTOG(98-02) (Coordinating Group) |
|
| Medical Oncology Mark R. Gilbert, M.D. (404) 727-3818 FAX (404) 727-3157 |
Radiation Oncology | Edward G. Shaw, M.D. Wake Forest University School of Medicine Medical Center Blvd. Winston-Salem, NC 27157-1030 (336) 716-4647 FAX (336) 716-5972 |
| NCCTG (R9802) Radiation Oncology Paul D. Brown, M.D. (507) 284-2949 FAX (507) 284-0079 |
Medical Oncology | Jan C. Buckner, M.D. (507) 284-4320 FAX (507) 284-1803 |
| Medical Oncology Jan C. Buckner, M.D. (507) 284-4320 FAX (507) 284-1803 |
Neuro-Oncology | Geoffrey R. Barger, M.D. (313) 577-1242 FAX (313) 745-4216 |
| SWOG(R9802) Radiation Oncology Keith J. Stelzer, M.D., Ph.D. (206) 548-4115 FAX (206) 548-6218 |
Neuropathology | Stephen W. Coons, M.D. (602) 406-7088 FAX (602) 406-7169 |
| Medical Oncology Geoffrey R. Barger, M.D. (313) 577-1242 FAX (313) 745-4216 |
Neuroradiology | Peter E. Ricci, M.D. (303) 788-8734 FAX (303) 788-6546 |
| Neurosurgery | Dennis E. Bullard, M.D. (919) 785-3500 FAX (9190 783-7810 | |
| Activation Date: | October 31, 1998 | |
| Closure Date: | June 27, 2002 | |
| Version Date: | August 18, 2003 (Broadcast: 9/15/03) Includes Revision 1 |
| This protocol was designed and developed by the Radiation Therapy Oncology Group (RTOG) of the American College of Radiology (ACR). It is intended to be used only in conjunction with institution-specific IRB approval for study entry. No other use or reproduction is authorized by RTOG nor does RTOG assume any responsibility for unauthorized use of this protocol. |
RTOG 98-02
A PHASE II STUDY OF OBSERVATION IN FAVORABLE LOW-GRADE GLIOMA AND PHASE III STUDY OF RADIATION WITH OR WITHOUT PCV CHEMOTHERAPY IN UNFAVORABLE LOW-GRADE GLIOMA
SCHEMA

| RTOG Institution # | ___________ | |
| RTOG 98-02 | ELIGIBILITY CHECK (8/18/03) | |
| RTOG Case # | ___________ | |
| Completed by | _______________________________ | Date | ____________________ |
| Oligo-Astros | Oligodendrogliomas | |
| Median (yr) 4.7 | 7.1 | 9.8 |
| 2-yr (%) 80 | 89 | 93 |
| 5-yr (%) 46 | 63 | 73 |
| 10-yr (%) 17 | 33 | 49 |
| 15-yr (%) 17 | 17 | 49 |
| Series | Age | Survival Median (Yrs.) |
| Eyre et al. | < 30 30-49 > 50 | Not Reached 5.5 1.6 |
| Medberry et al. | < 40 > 40 | 6.75 1.0 |
| Piepmeier | < 40 > 40 | 8.7 4.9 |
| Shaw et al. | < 35.5 > 35.5 | 6.3 4.2 |
| Series | Extent of Resection | 5-yr Survival | Mean Survival |
| Janny et al. | Gross Total Subtotal/Biopsy | 88% 57% | |
| North et al. | Gross Total Subtotal Biopsy | 85% 64% 43% | |
| Philippon et al. | Gross Total Subtotal Biopsy | 80% 50% 45% | |
| Piepmeier | Gross Total Subtotal Biopsy | 8.12 yrs 7.08 yrs 5.88 yrs |
| Series | Postoperative Radiation | 5-yr Survival | 10-yr Survival | Median Survival |
| Leighton et al. | No (Surgery only) Yes | 84% 62% | 70% 35% | 13 yrs 8 yrs |
| Philippon et al. | No Yes | 65% 55% | ||
| Piepmeier | No Yes | 8.76 yrs. 6.45 yrs | ||
| Shaw et al. | No Yes (< 53 Gy) Yes (> 53 Gy) | 32% 47% 68% | ||
| Shibamoto et al. | No Yes | 37% 60% |
| DRUG | DOSE | ROUTE | SCHEDULE |
| Procarbazine CCNU Vincristine | 60 mg/m2 110 mg/m2 1.4 mg/m2* | p.o. p.o. i.v. | Days 8- 21 Day 1 Days 8,29 |
| Absolute Granulocyte (nadir) | Platelet Count (nadir) | Dose Next Cycle CCNU & Procarbazine | |
| > 0.5 x 109/L (> 500) | and | > 50 x 109/L (> 50,000) | No change |
| < 0.5 x 109/L (< 500) | or | < 50 x 109/L (< 50,000) | Reduce previous cycle's dose by 25% |
| Absolute Granulocyte Count (at retreatment) | Platelet Count(at retreatment) | Dose This Cycle CCNU & Procarbazine | |
| > 1.5 x 109/L (> 1500) | and | > 100 x 109/L (> 100,000) | Proceed - dose dictated by nadir counts |
| < 1.5 x 109/L (< 1500) | or | < 100 x 109/L (< 100,000) | Delay treatment until hematologic recovery |
| Grades 4-5 unexpected1 | Death due to RX or within 30 days of RX2 | |
| ECOG ADR Form to NCI within 10 days | X | |
| ECOG ADR Form to ECOG Coordinating Center within 10 days | X | X |
| Notify local IRB within 10 days | X | X |
| NCI/CTEP Secondary AML/MDS Report Form 1 | ECOG Second Primary Form2 (Form #630) | |
| AML/MDS | X | |
| All other secondary cancers | X |
|
NCI Telephone Number: (301) 230-2330 NCI FAX: (301) 230-0159 NCI Mailing Address IDB P.O. Box 30012 Bethesda, MD 20824 |
ECOG Telephone Number: (617) 632-3610
ECOG FAX: (617) 632-2990 ECOG Mailing Address: ECOG Coordinating Center ATTN: ADR Frontier Science 303 Boylston Street Brookline, MA 02445-7648 |
| Parameter | On-Study | q 4 mos x 1 yr | q 6 mos x 2 yrs | q year |
| Central Path Review (pre randomization) | X | |||
| Clinical Assessment, incl. KPS & NFS | X | X | X | X |
| Record Steroid & Anticonvulsant Doses | X | X | X | X |
| MRI without and with Contrast | Xa,b | X | X | X |
| Mini-Mental Status Exam | X | X | X | X |
| Parameter | On-Study | At Completion of RT | q 4 mos x 1 yr | q 6 mos x 2 yrs | q year |
| Central Path Review (pre randomization) | X | ||||
| Clinical Assessment, incl. KPS & NFS | X | X | X | X | X |
| Record Steroid and Anticonvulsant Doses | X | X | X | X | X |
| Hematology: Hgb, WBC, diff, AGC, plts | X | ||||
| Biochemistry: Na, K, creatinine, SGOT (AST), SGPT, alk phos., total Bili, glucose | X | ||||
| MRI without and with Contrast | Xb | X | X | X | |
| Chest X-ray | Xc | ||||
| Pulmonary Functionsd | X | ||||
| Pregnancy Teste | X | ||||
| Mini-Mental Status Exam | X | X | X | X | X |
| Toxicity Evaluation | X | X | X | X |
| Parameter | On-Study | At end of RT | Pre-cycles 1-6 | Pre-cycles 3&5 | 4 mos after end of last cycle of chemo | q 6 mos x 2 yrs | q year |
| Central Path Review (pre randomization) | X | ||||||
| Clinical Assessment incl KPS & NFS | X | X | X | X | X | X | |
| Record Steroid & Anticonvulsant Doses | X | X | X | X | X | X | |
| Hematology: Hgb, WBC, diff, AGC, plts | X | X (and weekly during PCV) | X | X | X | ||
| Biochemistry: Na, K, creatinine, SGOT (AST), SGPT, alk phos., total Bili, glucose | X | X | Xc | Xc | Xc | ||
| MRI without and with Contrast | Xb | X | X | X | X | ||
| Chest X-ray | Xc | ||||||
| Pulmonary Functionsd | X | Xd | |||||
| Pregnancy Teste | X | ||||||
| Mini-Mental Status Exam | X | X | X | X | X | X | |
| Toxicity Evaluation | X | X | X | X | X | X |
| Item | Due |
| Demographic Form (A5) Pathology Checklist (P4) (copy, original to reviewer) Specimen Transmittal Form (ST) (copy, original to reviewer) Initial Evaluation Form (I1) Pathology Report (P1) Pathology Slides/Blocks (P2) Initial Mini-Mental Status Evaluation (MS) Pre-op MRI and post-op MRI scans (C1) and reports (C3) | Within 2 weeks of study entry |
| Radiotherapy Form (T1) Complete treatment record (T5) Isodose Curves (T6) (see Section 6.3 for details) | Within 2 weeks of RT end (Arms 2 & 3) |
| Follow-up MRI scans (C2) and reports (C3) | At 4 months post RT |
| Chemotherapy Flowsheet (M1) | At the end of each cycle and 3 months after day 29 of last cycle |
| Initial Followup-Form (FS) Mini-Mental Status Evaluation (MS) | At end of RT and at 90 days from the start of RT (Arms 2 and 3) |
| Follow-up MRI scans (C2) and reports (C3) | At regression, progression, and at > grade 3 neurotoxicity |
| Follow-up Form (F1) Mini-Mental Status Evaluation (MS) | q 4 mo x 1 yr, q 6 mo x 2 yr then annually. Also at progression /relapse and death (F1 only). |
| Autopsy Report (D3) | As applicable |
| Total Number of Deaths | Null Hypothesis | Alternative |
| 20 | 0.00004 | 0.86 |
| 40 | 0.0026 | 0.336 |
| 60 | 0.011 | 0.0942 |
| American Indian or Alaskan Native | Asian or Pacific Islander | Black, not of Hispanic Origin | Hispanic | White, not of Hispanic Origin | Other or Unknown | Total | |
| Female | 0 | 1 | 6 | 6 | 80 | 0 | 93 |
| Male | 0 | 2 | 11 | 6 | 140 | 0 | 159 |
| Unknown | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 3 | 17 | 12 | 220 | 0 | 252 |