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Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

A Phase II Evaluation of Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01060007
Enrollment
80
Registered
2010-02-01
Start date
2009-11-30
Completion date
2014-09-30
Last updated
2017-03-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rectal Neoplasms

Brief summary

To determine if short course radiotherapy followed by chemotherapy can maintain morbidity at or below levels reported with concurrent 5FU, oxaliplatin, and radiotherapy, while maintaining response rates comparable to what would be expected with radiotherapy and concurrent chemotherapy.

Detailed description

Our principal objectives in this trial will be to determine if short course radiotherapy followed by chemotherapy can maintain morbidity at or below levels reported with concurrent 5FU (oral capecitabine if 5FU is unavailable), oxaliplatin, and radiotherapy, while maintaining response rates comparable to what would be expected with radiotherapy and concurrent chemotherapy. If we can establish a T stage downstaging rate that is significantly better than 50% and if acute tolerance is acceptable, then we would consider this study as having provided sufficient pilot data to support including this approach as an arm in a multi-institution phase III trial. The long-term goal is improved overall control of disease by delivering better chemotherapy earlier.

Interventions

RADIATIONExternal beam radiation
DRUGOxaliplatin
DRUGLeucovorin
DRUG5-FU
DRUGCapecitabine

Sponsors

Washington University School of Medicine
Lead SponsorOTHER

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

* Biopsy proven adenocarcinoma of the rectum * Patient evaluated by surgeon and found to be a potential surgical candidate. Since the primary objectives are response to chemoradiation and acute toxicity, lesions which are initially unresectable are eligible-provided the surgeon feels that, if there is sufficient response, surgery could become feasible. * Clinical evidence of T3 or T4 disease. This can be by imaging studies (see or by physical findings (tethering on palpation for T3 lesions or invasion of a neighboring organ for T4 lesions) * Karnofsky Performance Status at \>60 * Laboratory criteria: * Absolute neutrophil count \>= 1.5 K * Platelets \>= 100 K * Total Bilirubin \<= 2.0; * SGOT and Alkaline Phosphatase \<= 2 x upper limit of normal * Creatinine \< 2.0 * Hemoglobin \>= 8.0 * Informed consent signed * Tumor measurable in at least one dimension. This may be, e.g. length and/or width measured endoscopically or on digital rectal examination, and maximum rectal wall thickness determined by imaging studies. * Estimated longevity at least 12 months * Patients with distant metastatic disease will be eligible if they satisfy all other conditions

Exclusion criteria

* Pregnant women, children \< 18 years, or patients unable to give informed consent * Patients with a past history of pelvic radiotherapy. * Patients with any other malignancy within the past 5 years except: skin cancer or in-situ cervical cancer * Patients with known allergy/intolerance to 5FU, Leucovorin, Oxaliplatin, Capecitabine * Prior chemotherapy for colorectal cancer. * Grade \>= 2 peripheral neuropathy * Any condition which, in the opinion of the treating medical oncologist, renders the patient unfit for 5FU (oral capecitabine if 5FU is unavailable), Leucovorin, Oxaliplatin chemotherapy

Design outcomes

Primary

MeasureTime frameDescription
Rate of T Stage DownstagingMean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)T stage downstaging is defined as clinical pretreatment American Joint Committee on Cancer T stage (cT) being greater than pathologic T stage at surgery (ypT).
Preoperative Gastrointestinal MorbidityMean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)As measured by participants who experience grade 3 or higher gastrointestinal morbidity

Secondary

MeasureTime frameDescription
Local Control30 months* Kaplan-Meier projections * Local control = control of primary tumor
Rate of Overall Control1 year—
Incidence of Any Late Grade 3 or Higher MorbidityPreoperative (mean time from start of radiation to surgery 17.3 weeks (SD +/- 2.9 weeks)—
Freedom From Disease Relapse30 monthsKaplan-Meier projections.
Determine Quality of Anorectal FunctionUp to 1 yearAnorectal function was measured by the participant's response to the FACT-C questionnaire question I have control of my bowels. The answers ranged from 0=not at all to 4=very much.
Rate of Locoregional Control1 year—
Incidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity1 year (completion of all treatment)—

Countries

United States

Participant flow

Recruitment details

The study opened to participant enrollment on 11/10/2009 and closed to participant enrollment on 04/18/2012.

Participants by arm

ArmCount
Neoadjuvant Radiation Followed by FOLFOX
Radiation - 20 Gy in 5 fractions to regional nodes. 25 Gy in the same 5 fractions to macroscopic disease. This is given over 1 week. FOLFOX Chemotherapy - after two weeks rest - oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 IV/2 hours followed sequentially by 5FU 400 mg/m2 IV push and 5FU 2400 mg/m2 over 46 hour CIVI. Repeat every other week for a total of 4 courses (this equals 6 weeks). If 5-FU is unavailable -- oral capecitabine can be given as 1000 mg/m2 BID on days 1-7 every 14 days.
76
Total76

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyInevaluable for response at surgery3
Overall StudyWithdrawal by Subject1

Baseline characteristics

CharacteristicNeoadjuvant Radiation Followed by FOLFOX
Age, Continuous56.4 years
STANDARD_DEVIATION 1.3
Clinical M stage
cM0
69 participants
Clinical M stage
cM1
7 participants
Clinical N stage
cN+
59 participants
Clinical N stage
cN0
17 participants
Clinical T stage
cT3
69 participants
Clinical T stage
cT4
7 participants
Region of Enrollment
United States
76 participants
Sex: Female, Male
Female
22 Participants
Sex: Female, Male
Male
54 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
79 / 79
serious
Total, serious adverse events
4 / 79

Outcome results

Primary

Preoperative Gastrointestinal Morbidity

As measured by participants who experience grade 3 or higher gastrointestinal morbidity

Time frame: Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)

Population: One patient was inevaluable for primary objectives because patient withdrew consent after completing radiation therapy, refused chemotherapy, and underwent a lesion resection 7 weeks after radiation therapy.

ArmMeasureValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXPreoperative Gastrointestinal Morbidity7 participants
Primary

Rate of T Stage Downstaging

T stage downstaging is defined as clinical pretreatment American Joint Committee on Cancer T stage (cT) being greater than pathologic T stage at surgery (ypT).

Time frame: Mean number of weeks before surgery 17.3 (SD +/- 2.9 weeks)

ArmMeasureValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXRate of T Stage Downstaging71 percentage of participants
Secondary

Determine Quality of Anorectal Function

Anorectal function was measured by the participant's response to the FACT-C questionnaire question I have control of my bowels. The answers ranged from 0=not at all to 4=very much.

Time frame: Up to 1 year

Population: Participants who had an ostomy were not included in this outcome measure. Participants who did not complete FACT-C questionnaire at a specific timepoint were not included in that timepoint.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Neoadjuvant Radiation Followed by FOLFOXDetermine Quality of Anorectal Function4 = very much26 Participants
Neoadjuvant Radiation Followed by FOLFOXDetermine Quality of Anorectal Function1 = a little bit3 Participants
Neoadjuvant Radiation Followed by FOLFOXDetermine Quality of Anorectal Function2 = somewhat22 Participants
Neoadjuvant Radiation Followed by FOLFOXDetermine Quality of Anorectal Function0 = not at all7 Participants
Neoadjuvant Radiation Followed by FOLFOXDetermine Quality of Anorectal Function3 = quite a bit14 Participants
Pre-surgeryDetermine Quality of Anorectal Function1 = a little bit4 Participants
Pre-surgeryDetermine Quality of Anorectal Function3 = quite a bit21 Participants
Pre-surgeryDetermine Quality of Anorectal Function0 = not at all4 Participants
Pre-surgeryDetermine Quality of Anorectal Function2 = somewhat8 Participants
Pre-surgeryDetermine Quality of Anorectal Function4 = very much22 Participants
1 Year Post-treatmentDetermine Quality of Anorectal Function3 = quite a bit7 Participants
1 Year Post-treatmentDetermine Quality of Anorectal Function0 = not at all2 Participants
1 Year Post-treatmentDetermine Quality of Anorectal Function4 = very much5 Participants
1 Year Post-treatmentDetermine Quality of Anorectal Function1 = a little bit4 Participants
1 Year Post-treatmentDetermine Quality of Anorectal Function2 = somewhat13 Participants
Secondary

Freedom From Disease Relapse

Kaplan-Meier projections.

Time frame: 30 months

Population: These include all cMO evaluable cases only.

ArmMeasureValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXFreedom From Disease Relapse87 percentage of participants
Secondary

Incidence of Any Late Grade 3 or Higher Morbidity

Time frame: Preoperative (mean time from start of radiation to surgery 17.3 weeks (SD +/- 2.9 weeks)

Population: One patient was inevaluable for primary objectives because patient withdrew consent after completing radiation therapy, refused chemotherapy, and underwent a lesion resection 7 weeks after radiation therapy.

ArmMeasureGroupValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXIncidence of Any Late Grade 3 or Higher MorbidityNon-hematologic toxicities16 participants
Neoadjuvant Radiation Followed by FOLFOXIncidence of Any Late Grade 3 or Higher MorbidityHematologic toxicities21 participants
Secondary

Incidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity

Time frame: 1 year (completion of all treatment)

ArmMeasureValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXIncidence of Post Chemoradiotherapy Grade 3 or Higher Morbidity21 participants
Secondary

Local Control

* Kaplan-Meier projections * Local control = control of primary tumor

Time frame: 30 months

ArmMeasureValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXLocal Control95 percentage of participants
Secondary

Rate of Locoregional Control

Time frame: 1 year

ArmMeasureValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXRate of Locoregional Control96 percentage of participants
Secondary

Rate of Overall Control

Time frame: 1 year

ArmMeasureValue (NUMBER)
Neoadjuvant Radiation Followed by FOLFOXRate of Overall Control89 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026