Rectal Cancer
Conditions
Keywords
SHORT, short course radiation,, TASOX
Brief summary
TASOX can be safely and efficaciously delivered after short course radiation, resulting in significant pathologic downstaging, allowing for an R0 pelvic resection, and providing local control in appropriately selected stage II/III rectal cancer patients treated with contemporary TME-based surgery.
Detailed description
In this phase II study patients will be treated with short-course preoperative irradiation (25 Gy in five fractions of 5 Gy) followed by 6 (six) 2-week cycles of TASOX followed by total mesorectal excision (TME) for patients with resectable rectal cancer (clinical T3c/dN0, T3c/dN1, T2N1). Eligible study subjects include adults who are candidates for curative intent sphincter-sparing surgery and lack high risk features such as tumor encroaching upon the mesorectal-fascia or low tumors who need an Abdominal-Perineal Resection (APR).
Interventions
DRUGTAS 102
Oral medication over Days 1-5
DRUGOxaliplatin
Administered by intravenous infusion over 2 hours on day 1
Sponsors
Taiho Oncology
Providence Health & Services
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
1. Age of at least 18 years. 2. Newly diagnosis of rectal adenocarcinoma. 3. ECOG Performance Status (PS): 0, 1 or 2. 4. Candidate for sphincter-sparing surgical resection prior to initiation of neoadjuvant therapy according to the primary surgeon. 5. Clinical Stage: T1/N1, T2/N1, T3/N1, T3c/dN0. 6. Absence of metastatic disease. Clinical staging is based on physical exam by the primary surgeon, CT scan of the chest/abdomen, and pelvic MRI. Node positivity determination: Entry criteria nodes will be measured in short-axis diameter and for the purposes of study entry will be considered positive if 8 mm or greater in short axis. Radiographic N2 status is estimated as: 4 or more nodes that measure 8mm or more in short-axis. Radiographic N1 status is estimated as: fewer than 4 lymph nodes that measure 8 mm or greater in short axis but 1 or more lymph nodes that measure 8 mm or greater. Nodal Metastatic Disease: nodal stations considered suspicious for metastatic disease (M1) for rectal cancer are common iliac, external iliac and inguinal nodes. 7. No evidence of tumor that is adherent to the mesorectal fascia and the ability to perform a curative intent sphincter-sparing TME resection at diagnosis. See exclusion criterion 4 8. The following laboratory values obtained ≤ 28 days prior to registration. * Platelet count ≥ 100,000/mm\^3 * Hemoglobin \> 8.0 g/dL * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) * SGOT (AST) ≤ 3 x ULN * SGPT (ALT) ≤ 3 x ULN * Creatinine ≤1.5 x ULN 9. Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only. 10. A patient of child-bearing potential is willing to employ adequate contraception. It includes any of the followings: abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom). See exclusion criterion 8 11. Provide informed written consent. 12. Willing to return to enrolling medical site for all study assessments.
Exclusion criteria
1. Clinical T4 tumors. 2. Clinical N2 disease estimated as four or more lymph nodes that are ≥8 mm. 3. Primary surgeon indicates need for abdominoperineal (APR) at baseline. 4. Evidence that the tumor is adherent to or invading the mesorectal fascia on imaging studies such that the surgeon would not be able to perform an R0 resection (one with negative margins). Distance of the Tumor from the Mesorectal Fascia: Patients with tumors with a distance of 1mm or less from the mesorectal fascia reflection have threatened radial margins and are ineligible. 5. Tumor is causing symptomatic bowel obstruction or patients who have had a temporary diverting ostomy are ineligible. 6. Chemotherapy within 5 years prior to registration. (Hormonal therapy is allowable if the disease free interval is ≥ 5 years.) 7. Any prior pelvic radiation. 8. Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception 9. Co-morbid illnesses or other concurrent disease which, in the judgment of the treating investigator obtaining informed consent, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neoadjuvant Response (NAR) Score | Through study completion, an average of 6 months | Determine whether pre-operative short-course radiation therapy (SRT) and 6 cycles of TASOX offers condensed radiation and total neoadjuvant therapy for intermediate risk rectal cancer. Measurement of efficacy is the NAR score, where the required elements of the NAR score are: clinical tumor stage (cT), pathologic tumor stage (pT), pathological nodal stage (pN). For patients with a cCR who opted for non-operative management, for the purposes of the NAR score, those patients were assigned a pT0 and pN0 score if they did not experience tumor regrowth or require subsequent TME surgical resection during the time of the study. The NAR score ranges from 0-100, where lower NAR scores are considered favorable as opposed to higher scores which would indicate a worse prognosis. NAR calculation as follows: NAR=\[5 pN- 3(cT-pT)+12\]\^2/9.61 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | Through study completion, an average of 6 months | The secondary objective is to describe Incidence of Treatment-Emergent Adverse Events and surgery complications among treated subjects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TAS102 Plus Oxaliplatin Oxaliplatin 85mg/m2 IV over 2 hours and TAS-102 (35 mg/m2/dose) orally BID
TAS 102: Oral medication over Days 1-5
Oxaliplatin: Administered by intravenous infusion over 2 hours on day 1 | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | TAS102 Plus Oxaliplatin |
|---|---|
| Age, Continuous | 66 years |
| Baseline radiographic M stage cM0 | 13 Participants |
| Baseline radiographic M stage cM1 | 0 Participants |
| Baseline radiologic N stage cN0 | 5 Participants |
| Baseline radiologic N stage cN1 | 8 Participants |
| Baseline radiologic N stage cN2 | 0 Participants |
| Baseline radiologic T stage cT1 | 0 Participants |
| Baseline radiologic T stage cT2 | 0 Participants |
| Baseline radiologic T stage cT3a/b | 12 Participants |
| Baseline radiologic T stage cT3c/d | 1 Participants |
| Baseline radiologic T stage cT4 | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 1 / 13 |
Outcome results
Primary
Neoadjuvant Response (NAR) Score
Determine whether pre-operative short-course radiation therapy (SRT) and 6 cycles of TASOX offers condensed radiation and total neoadjuvant therapy for intermediate risk rectal cancer. Measurement of efficacy is the NAR score, where the required elements of the NAR score are: clinical tumor stage (cT), pathologic tumor stage (pT), pathological nodal stage (pN). For patients with a cCR who opted for non-operative management, for the purposes of the NAR score, those patients were assigned a pT0 and pN0 score if they did not experience tumor regrowth or require subsequent TME surgical resection during the time of the study. The NAR score ranges from 0-100, where lower NAR scores are considered favorable as opposed to higher scores which would indicate a worse prognosis. NAR calculation as follows: NAR=\[5 pN- 3(cT-pT)+12\]\^2/9.61
Time frame: Through study completion, an average of 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAS102 Plus Oxaliplatin | Neoadjuvant Response (NAR) Score | 9.31 Calculated score | Standard Deviation 13.41 |
Secondary
Safety and Tolerability
The secondary objective is to describe Incidence of Treatment-Emergent Adverse Events and surgery complications among treated subjects.
Time frame: Through study completion, an average of 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAS102 Plus Oxaliplatin | Safety and Tolerability | Number of patients who experienced Grade 3 or 4 adverse events | 7 participants |
| TAS102 Plus Oxaliplatin | Safety and Tolerability | Number of patients who experienced post-operative complications | 0 participants |