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Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
Phase 3 trial testing Cyclophosphamide in Adult Rhabdomyosarcoma in 481 participants. Completed in 31 December 2022.
| Lead sponsor | Children's Oncology Group |
|---|---|
| Phase | Phase 3 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | randomized |
| Design | parallel |
| Masking | none |
| Primary purpose | treatment |
| Enrollment | 481 |
| Start date | 26 December 2006 |
| Primary completion | 31 December 2014 |
| Estimated completion | 31 December 2022 |
| Sites | 226 locations across New Zealand, Canada, Puerto Rico, Australia, Switzerland, United States |
Children's Oncology Group — full company profile →
Under 49, any sex, with Adult Rhabdomyosarcoma or Childhood Alveolar Rhabdomyosarcoma. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Probability of no relapse, secondary malignancy, or death after 4 year in the study
| Group | Value | 95% CI |
|---|---|---|
| Vincristine, Dactinomycin, Cyclophosphamide (VAC) | 0.6255 | 0.5575 – 0.6934 |
| VAC Alternating With Vincristine, Irinotecan (VI) | 0.5874 | 0.5178 – 0.6569 |
Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at \> 4 weeks; Partial Response (PR): At least 64% decrease in volume compared to the baseline; Overall Response (OR) = CR + PR.
| Group | Value | 95% CI |
|---|---|---|
| Vincristine, Dactinomycin, Cyclophosphamide (VAC) | 0.6667 | 0.6047 – 0.7287 |
| VAC Alternating With Vincristine, Irinotecan (VI) | 0.6726 | 0.6114 – 0.7337 |
Probability of being alive after 4 years in the study.
| Group | Value | 95% CI |
|---|---|---|
| Vincristine, Dactinomycin, Cyclophosphamide (VAC) | 0.7293 | 0.6669 – 0.7917 |
| VAC Alternating With Vincristine, Irinotecan (VI) | 0.7223 | 0.6583 – 0.7862 |
Compare 4-year EFS using eligible participants only to the historical rate of 0.65 with IRSI-V. The 4-year EFS is probability of no relapse, secondary malignancy, or death after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.65.
| Group | Value | 95% CI |
|---|---|---|
| Vincristine, Dactinomycin, Cyclophosphamide (VAC) | 0.6255 | 0.5575 – 0.6934 |
Compare 2-year local failure rate to the historical rate of 0.13 with IRSI-V. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.13.
| Group | Value | 95% CI |
|---|---|---|
| Vincristine, Dactinomycin, Cyclophosphamide (VAC) | 0.1757 | 0.1256 – 0.2257 |
Compare 4-year OS using eligible participants only to the historical rate of 0.70 with IRSI-V. The 4-year OS is probability of being alive after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.70.
| Group | Value | 95% CI |
|---|---|---|
| Vincristine, Dactinomycin, Cyclophosphamide (VAC) | 0.7293 | 0.6669 – 0.7917 |
Grade 3 or 4 nausea, diarrhea, dehydration, radiation dermatitis, mucositis due to radiation. Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.
| Group | Value | 95% CI |
|---|---|---|
| Vincristine, Dactinomycin, Cyclophosphamide (VAC) | 0.2072 | 0.1539 – 0.2605 |
| VAC Alternating With Vincristine, Irinotecan (VI) | 0.3673 | 0.3044 – 0.4301 |
The toxicity rates will be estimated for each phase and course of treatment, and will be compared to the fixed rates under D9803 using one-sided lower confidence intervals for a single proportion without adjustment for multiple comparisons.
| Group | Value | 95% CI |
|---|---|---|
| VAC (Weeks 1-15) | 58 | |
| VAC (Weeks 31 - 43) | 54 |
| Group | Value | 95% CI |
|---|---|---|
| VAC (Weeks 1-15) | 30 | |
| VAC (Weeks 31 - 43) | 17 |
| Group | Value | 95% CI |
|---|---|---|
| VAC (Weeks 1-15) | 6 | |
| VAC (Weeks 31 - 43) | 1 |
| Group | Value | 95% CI |
|---|---|---|
| VAC (Weeks 1-15) | 27 | |
| VAC (Weeks 31 - 43) | 63 |
| Group | Value | 95% CI |
|---|---|---|
| VAC (Weeks 1-15) | 9 | |
| VAC (Weeks 31 - 43) | 2 |
4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study).
| Group | Value | 95% CI |
|---|---|---|
| % Change in SUVmax From Baseline to Week 4 < 40% | 0.2857 | 0.0000 – 0.6204 |
| % Change in SUVmax From Baseline to Week 4 >= 40% | 0.6364 | 0.4354 – 0.8374 |
4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study)
| Group | Value | 95% CI |
|---|---|---|
| % Change in SUVmax From Baseline to Week 15 < 40% | 0.6667 | 0.2895 – 1.0000 |
| % Change in SUVmax From Baseline to Week 15 >= 40% | 0.5686 | 0.4303 – 0.7070 |
Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.
| Group | Value | 95% CI |
|---|---|---|
| UGT1A1 Genotype 6/6 | 16 | |
| UGT1A1 Genotype 6/7 | 22 | |
| UGT1A1 Genotype 7/7 | 4 |
| Group | Value | 95% CI |
|---|---|---|
| UGT1A1 Genotype 6/6 | 5 | |
| UGT1A1 Genotype 6/7 | 14 | |
| UGT1A1 Genotype 7/7 | 5 |
| Group | Value | 95% CI |
|---|---|---|
| PAX3 | 0.51 | 0.39 – 0.64 |
| PAX7 | 0.66 | 0.37 – 0.94 |
Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Vincristine, Dactinomycin,… | VAC Alternating With VI |
|---|---|---|---|
| Nervous system disorders - Other, specify | Nervous system disorders | — | — |
| Death NOS | General disorders | — | — |
| Mucositis oral | Gastrointestinal disorders | — | — |
| Alanine aminotransferase increased | Investigations | — | — |
| Anemia | Blood and lymphatic system disorders | — | — |
| Ascites | Gastrointestinal disorders | — | — |
| Aspartate aminotransferase increased | Investigations | — | — |
| Blood bilirubin increased | Investigations | — | — |
| Encephalopathy | Nervous system disorders | — | — |
| Esophagitis | Gastrointestinal disorders | — | — |
| Gastritis | Gastrointestinal disorders | — | — |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | — | — |
| Hepatic pain | Hepatobiliary disorders | — | — |
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | — | — |
| Hypokalemia | Metabolism and nutrition disorders | — | — |
| Hyponatremia | Metabolism and nutrition disorders | — | — |
| Intracranial hemorrhage | Nervous system disorders | — | — |
| Lymphocyte count decreased | Investigations | — | — |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | — | — |
| Oral pain | Gastrointestinal disorders | — | — |
| Pharyngeal mucositis | Respiratory, thoracic and mediastinal disorders | — | — |
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | — | — |
| Platelet count decreased | Investigations | — | — |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | — | — |
| Radiation recall reaction (dermatologic) | Injury, poisoning and procedural complications | — | — |
| Reaction | System | Vincristine, Dactinomycin,… | VAC Alternating With VI |
|---|---|---|---|
| Neutrophil count decreased | Investigations | — | — |
| Anemia | Blood and lymphatic system disorders | — | — |
| White blood cell decreased | Investigations | — | — |
| Platelet count decreased | Investigations | — | — |
| Febrile neutropenia | Blood and lymphatic system disorders | — | — |
| Lymphocyte count decreased | Investigations | — | — |
| Diarrhea | Gastrointestinal disorders | — | — |
| Mucositis oral | Gastrointestinal disorders | — | — |
| Infections and infestations - Other, specify | Infections and infestations | — | — |
| Anorexia | Metabolism and nutrition disorders | — | — |
| Hypokalemia | Metabolism and nutrition disorders | — | — |
| Peripheral motor neuropathy | Nervous system disorders | — | — |
| Vomiting | Gastrointestinal disorders | — | — |
| Nausea | Gastrointestinal disorders | — | — |
| Dehydration | Metabolism and nutrition disorders | — | — |
| Weight loss | Investigations | — | — |
| Alanine aminotransferase increased | Investigations | — | — |
| Peripheral sensory neuropathy | Nervous system disorders | — | — |
| Hyponatremia | Metabolism and nutrition disorders | — | — |
| Catheter related infection | Infections and infestations | — | — |
| Abdominal pain | Gastrointestinal disorders | — | — |
| Aspartate aminotransferase increased | Investigations | — | — |
| Fever | General disorders | — | — |
| Hyperglycemia | Metabolism and nutrition disorders | — | — |
| Enterocolitis infectious | Infections and infestations | — | — |
| Urinary tract infection | Infections and infestations | — | — |
| Pain | General disorders | — | — |
| Hypophosphatemia | Metabolism and nutrition disorders | — | — |
| Oral pain | Gastrointestinal disorders | — | — |
| Skin infection | Infections and infestations | — | — |
| Constipation | Gastrointestinal disorders | — | — |
| Dermatitis radiation | Injury, poisoning and procedural complications | — | — |
| Dysphagia | Gastrointestinal disorders | — | — |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | — | — |
| Ileus | Gastrointestinal disorders | — | — |
| Fatigue | General disorders | — | — |
| Anaphylaxis | Immune system disorders | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — |
| Colitis | Gastrointestinal disorders | — | — |
| Device related infection | Infections and infestations | — | — |
Most-reported serious reactions: Nervous system disorders - Other, specify, Death NOS, Mucositis oral, Alanine aminotransferase increased, Anemia, Ascites, Aspartate aminotransferase increased, Blood bilirubin increased.
Data from ClinicalTrials.gov NCT00354835 adverse events section.
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with radiation therapy in treating patients with rhabdomyosarcoma.
8 peer-reviewed publications reference this trial (live from Europe PMC):
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