Chondrosarcomas, Chordomas
Conditions
Keywords
Age 18 or greater, No prior radiation
Brief summary
The objectives of this study are 1) To evaluate the feasibility and acute side effects of proton therapy for chordomas and chondrosarcomas and 2) To evaluate clinical outcomes and long term side effects of proton beam radiation for treatment of chordomas and chondrosarcomas.
Detailed description
This trial will be conducted in two phases: a feasibility then a phase II trial. Once feasibility and safety are established in the first 12 pts. the phase II study will begin. Proton therapy at standard doses is not known to improve clinical outcome but will likely reduce fatigue and toxicity.
Interventions
RADIATIONProton Therapy
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of chordoma or chondrosarcoma. * Patients must have no evidence of metastatic disease based on routine imaging (CT or MRI of the chest/abdomen/pelvis, bone scan, etc.) * Patients must have an ECOG score equal to or less than 2. * Age ≥ 18 years. * Patients must be able to provide informed consent. * Adequate bone marrow function: WBC ≥ 4000/mm3, platelets ≥ 100, 000mm3 * Women of child-bearing potential as long as she agrees to use a recognized method of birth control (e.g. oral contraceptive , IUD, condoms or other barrier methods etc.) Hysterectomy or menopause must be clinically documented. * Tumors arising in the skull and spine.
Exclusion criteria
* Prior or simultaneous malignancies within the past two years (other than cutaneous squamous or basal cell carcinoma, melanoma in situ or thyroid carcinoma) * Patients with the following histologies are excluded: melanoma , other soft tissue or bony sarcomas, giant cell tumor aneurismal bone cyst or metastatic lesions from other histologies. * Pregnant women. * Actively being treated on any other therapeutic research study. * Tumors arising outside of the CNS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Proton RT for Chordomas and Chondrosarcomas | From enrollment to treatment completion or withdrawal, whichever occurred first, assessed up to 133 months | The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. The feasibility, as defined by ≥10% of patients experiencing either: unsatisfactory dosimetry, inability to complete all of his/her treatments within 10 days of estimated completion date and requiring no break \>5 days, and no greater than 20% of patients experiencing ≥grade 3 toxicity from RT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Toxicities | With in the 90 days from tx start date | Any grade 3 or higher toxicity observed within 90 days from start of therapy. |
| Late Toxicities | Every 3 months for 3 Years from the tx start date and assessed up to 133 months | Any grade 3 or higher toxicity observed later than 90 days from completion of therapy. Timepoints included below: Approx. 90 days from tx start. Follow-Up Months (approximately from completion of treatment) 3,6,9,12,15, 18, 21, 24 (approx.) Months 30, 36 (approximately from completion of treatment) Year 4 and 5 (approximately from completion of treatment) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proton Group Proton radiation total dose 72.00 to 79.2 Gy(RBE) in 40-44 fractions
Proton Therapy | 54 |
| Total | 54 |
Baseline characteristics
| Characteristic | Proton Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants |
| Age, Continuous | 54 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Histology Chondrosarcoma | 12 Participants |
| Histology Chordoma | 42 Participants |
| Lesion site Clivus/skull base | 39 Participants |
| Lesion site C spine | 3 Participants |
| Lesion site L spine | 1 Participants |
| Lesion site Sacrum/coccyx | 11 Participants |
| Lesion site T spine | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Region of Enrollment United States | 54 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 54 |
| other Total, other adverse events | 45 / 54 |
| serious Total, serious adverse events | 15 / 54 |
Outcome results
Primary
Feasibility of Proton RT for Chordomas and Chondrosarcomas
The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. The feasibility, as defined by ≥10% of patients experiencing either: unsatisfactory dosimetry, inability to complete all of his/her treatments within 10 days of estimated completion date and requiring no break \>5 days, and no greater than 20% of patients experiencing ≥grade 3 toxicity from RT.
Time frame: From enrollment to treatment completion or withdrawal, whichever occurred first, assessed up to 133 months
Population: Follow-up
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Group | Feasibility of Proton RT for Chordomas and Chondrosarcomas | >10% of patients experiencing unstatisfactory dosimetry or inability to complete his/her treatments | 3.7 percentage of patients did not meet this |
| Proton Group | Feasibility of Proton RT for Chordomas and Chondrosarcomas | 20% of patients experienceing >= grade 3 toxicity | 1.9 percentage of patients did not meet this |
Secondary
Acute Toxicities
Any grade 3 or higher toxicity observed within 90 days from start of therapy.
Time frame: With in the 90 days from tx start date
Population: Number of cases
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Group | Acute Toxicities | Cognitive disturbance | 3 Number of cases |
| Proton Group | Acute Toxicities | Voice alteration | 3 Number of cases |
| Proton Group | Acute Toxicities | Dysarthria | 1 Number of cases |
| Proton Group | Acute Toxicities | Fatigue | 37 Number of cases |
| Proton Group | Acute Toxicities | Radiation dermatitis | 28 Number of cases |
| Proton Group | Acute Toxicities | Headache | 14 Number of cases |
| Proton Group | Acute Toxicities | Alopecia | 9 Number of cases |
| Proton Group | Acute Toxicities | Insomnia | 9 Number of cases |
| Proton Group | Acute Toxicities | Paresthesia | 7 Number of cases |
| Proton Group | Acute Toxicities | Constipation | 7 Number of cases |
| Proton Group | Acute Toxicities | Pain | 4 Number of cases |
| Proton Group | Acute Toxicities | Dysphagia | 6 Number of cases |
| Proton Group | Acute Toxicities | Xerostomia | 4 Number of cases |
| Proton Group | Acute Toxicities | Diarrhea | 2 Number of cases |
| Proton Group | Acute Toxicities | Anorexia | 5 Number of cases |
| Proton Group | Acute Toxicities | Urinary (retention or incontinence) | 6 Number of cases |
| Proton Group | Acute Toxicities | Ataxia | 5 Number of cases |
| Proton Group | Acute Toxicities | Oral mucositis | 2 Number of cases |
| Proton Group | Acute Toxicities | Edema | 2 Number of cases |
| Proton Group | Acute Toxicities | Visual/blurry | 2 Number of cases |
| Proton Group | Acute Toxicities | Nerve palsy | 1 Number of cases |
| Proton Group | Acute Toxicities | Tinnitus | 1 Number of cases |
| Proton Group | Acute Toxicities | Dysgeusia | 5 Number of cases |
Secondary
Late Toxicities
Any grade 3 or higher toxicity observed later than 90 days from completion of therapy. Timepoints included below: Approx. 90 days from tx start. Follow-Up Months (approximately from completion of treatment) 3,6,9,12,15, 18, 21, 24 (approx.) Months 30, 36 (approximately from completion of treatment) Year 4 and 5 (approximately from completion of treatment)
Time frame: Every 3 months for 3 Years from the tx start date and assessed up to 133 months
Population: Number of cases
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Proton Group | Late Toxicities | Late Fatigue | 17 Number of cases |
| Proton Group | Late Toxicities | Late Headache | 8 Number of cases |
| Proton Group | Late Toxicities | Late Pain | 4 Number of cases |
| Proton Group | Late Toxicities | Late Loss of smell | 1 Number of cases |
| Proton Group | Late Toxicities | Late Cognitive disturbance | 2 Number of cases |
| Proton Group | Late Toxicities | Late Xerostomia | 1 Number of cases |
| Proton Group | Late Toxicities | Late Paresthesia | 5 Number of cases |
| Proton Group | Late Toxicities | Late Insomnia | 1 Number of cases |
| Proton Group | Late Toxicities | Late Diarrhea | 1 Number of cases |
| Proton Group | Late Toxicities | Late Neck edema | 1 Number of cases |
| Proton Group | Late Toxicities | Late Dysgeusia | 2 Number of cases |
| Proton Group | Late Toxicities | Late Ataxia | 5 Number of cases |
| Proton Group | Late Toxicities | Late Aphasia | 1 Number of cases |
| Proton Group | Late Toxicities | Late Radionecrosis of the brain | 3 Number of cases |
| Proton Group | Late Toxicities | Late Anorexia | 2 Number of cases |
| Proton Group | Late Toxicities | Late Dysphagia | 2 Number of cases |
| Proton Group | Late Toxicities | Late Muscle weakness | 1 Number of cases |
| Proton Group | Late Toxicities | Late Intranasal carotid blowout | 1 Number of cases |
| Proton Group | Late Toxicities | Late Osteoradionecrosis | 1 Number of cases |