NCT01515787 · CITED IN SOURCE DOCUMENTS

PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2, PHASE3
Status at capture: UNKNOWN
Registry last update: 2024-02-02

The standard treatment for locally advanced rectal cancer involves chemotherapy and radiation, known as 5FUCMT, (the chemotherapy drugs 5-fluorouracil/capecitabine and radiation therapy) prior to surgery. Although radiation therapy to the pelvis has been a standard and important part of treatment for rectal cancer and has been shown to decrease the risk of the cancer coming back in the same area in the pelvis, some patients experience undesirable side effects from the radiation and there have been important advances in chemotherapy, surgery, and radiation which may be of benefit. The purpose of this study is to compare the effects, both good and bad, of the standard treatment of chemotherapy and radiation to chemotherapy using a combination regimen known as FOLFOX, (the drugs 5-fluorouracil (5-FU), oxaliplatin and leucovorin) and selective use of the standard treatment, depending on response to the FOLFOX. The drugs in the FOLFOX regimen are all FDA (Food and Drug Administration) approved and have been used routinely to treat patients with advanced colorectal cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Pelvic R0 Resection Rate

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outcome · POSTED

DFS

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outcome · POSTED

Pathologic Complete Response

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outcome · POSTED

Overall Survival

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outcome · POSTED

Rates of Receiving Pre- or Post-operative 5FUCMT

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outcome · POSTED

Local Recurrence (TLR):

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outcome · POSTED

Neoadjuvant Rectal Score

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Registration Inclusion Criteria: 1. Age ≥ 18 years at diagnosis 2. Diagnosis of rectal adenocarcinoma 3. Radiologically measurable or clinically evaluable disease as defined in the protocol 4. ECOG Performance Status (PS): 0, 1 or 2 5. For this patient, the standard treatment recommendation in the absence of a clinical trial would be combined modality neoadjuvant chemoradiation followed by curative intent surgical resection 6. Candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy according to the primary surgeon 7. Primary surgeon is credentialed or is willing to be credentialed in Total Mesorectal Excision (TME), which entails submission of photos of a single TME specimen either before enrolling the first patient or by using the surgeon's 1st accrued case. 8. Clinical Stage: T2N1, T3N0, T3N1. * N2 disease is to be estimated as four or more lymph nodes that are ≥ 10 mm. * Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT or PET/CT scan of the chest/abdomen/pelvis and either a pelvic MRI or an ultrasound (ERUS). If a pelvic MRI is peformed, it is acceptable to perform CT of the chest/abdomen, ommitting CT imaging of the pelvis. 9. The following laboratory values obtained ≤ 28 days prior to registration: * Absolute neutrophil count (ANC) ≥ 1500/mm\^3 * 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 10. Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only 11. Patient of child-bearing potential is willing to employ adequate contraception 12. Provide informed written consent 13. Willing to return to enrolling medical site for all study assessments Registration Exclusion Criteria: 1. Clinical T4 tumors 2. Primary surgeon indicates need for abdominoperineal (APR) at baseline 3. 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) 4. Tumor is causing symptomatic bowel obstruction (patients who have had a temporary diverting ostomy are eligible). 5. Chemotherapy within 5 years prior to registration. Hormonal therapy is allowable if the disease free interval is ≥ 5 years. 6. Any prior pelvic radiation 7. Other invasive malignancy ≤ 5 years prior to registration. Exceptions are colonic polyps, non-melanoma skin cancer, ductal carcinoma in situ, bladder carcinoma in situ, or carcinoma-in-situ of the cervix. 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 clinician 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients will receive FOLFOX chemotherapy once every two weeks for 6 cycles total over a period of 12 weeks. After completing FOLFOX chemotherapy, the patient will have an MRI scan or endorectal ultrasound (ERUS) to examine the tumor. If the tumor has not decreased in size by at least 20%, the patient will receive 5FUCMT (radiation with chemotherapy). If the tumor has decreased in size by 20%, then the patient will proceed directly to surgery. If all borders of the tumor are normal post surgery, then the patient receives six additional cycles of FOLFOX chemotherapy. If all borders of the tumor are not normal then the patient receives chemoradiation therapy for 5.5 weeks after surgery. After chemoradiation, additional cycles of FOLFOX or similar chemotherapy will be recommended for 4 cycles or 8 weeks. Patient observation with follow up evaluations and event monitoring will occur up to 8 years post randomization.
intervention Names
Drug: FOLFOX (chemotherapy)
Other: 5 FUCMT (chemoradiation)
Procedure: surgery
Procedure: magnetic resonance imaging or endorectal ultrasound
label
Group 1
type
EXPERIMENTAL
description
Patients receive 5FUCMT including chemotherapy and radiation therapy for 5.5 weeks. Patients will be given either 5-fluorouracil or capecitabine and radiation therapy. After the chemoradiation therapy is completed, patients will proceed directly to surgery. Post-surgery, patients will receive FOLFOX chemotherapy once every two weeks for 8 cycles total over a period of 16 weeks. Patient observation with follow up evaluations and event monitoring will occur up to 8 years post randomization.
intervention Names
Drug: FOLFOX (chemotherapy)
Other: 5 FUCMT (chemoradiation)
Procedure: surgery
label
Group 2
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Group 1
Group 2
description
Oxaliplatin 85 mg/m\^2 IV over 2 hours on day 1, leucovorin 400 mg/m\^2 bolus IV over 2 hours on day 1 and 5-fluorouracil 400 mg/m\^2 bolus over 5-15 minutes then 2400 mg/m\^2 continual over 46-48 hours total dose IV on days 1-2. The treatment schedule repeats based on the group. Dose modifications are allowed based on adverse events.
name
FOLFOX (chemotherapy)
type
DRUG
arm Group Labels
Group 1
Group 2
description
5-fluorouracil 225 mg/m\^2 per day continuous IV infusion administered concurrently with radiation therapy for 5 or 7 days per week OR capecitabine 825 mg/m\^2 twice daily administered orally and concurrently with radiation therapy for 5 days per week. Dose modifications are allowed based on adverse events.
name
5 FUCMT (chemoradiation)
type
OTHER
arm Group Labels
Group 1
Group 2
description
low anterior resection with total mesorectal excision
name
surgery
type
PROCEDURE
arm Group Labels
Group 1
name
magnetic resonance imaging or endorectal ultrasound
type
PROCEDURE

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1194
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Number of Participants with Pelvic R0 Resection
measure
Pelvic R0 Resection Rate
time Frame
Up to 5 years
description
Disease-free Survival (DFS): The distribution of DFS by group will be estimated using the method of Kaplan-Meier. 5 year disease free rates by treatment group with confidence intervals based on Kaplan-Meier curves will be reported. Log-rank test will be used to compare DFS between two treatment groups. Hazard ratio with confidence interval will be estimated based on Cox proportional hazard model. The Cox proportional hazard model will be used for multivariate analysis.
measure
DFS
time Frame
Up to 5 years

secondary Outcomes

description
Pathologic Complete Response (pCR): The pCR rate is defined as number of patients who achieve pCR divided by total number of patients included in the analysis population (see definition in Section 16.3.3.1) in each group. Patients who didn't undergo surgery will be classified as non-pCR. Point estimate and confidence interval (according to approach of Duffy and Santner) will be calculated by treatment groups. Chi-square test will be used to compare the pCR rates between groups.
measure
Pathologic Complete Response
time Frame
Up to 8 years
description
Overall Survival (OS): OS is defined as time from randomization to the date of death due to all causes. The distribution of OS by group will be estimated using the method of Kaplan-Meier. Five year survival rates by treatment group with confidence intervals based on Kaplan-Meier curves will be reported. Logrank test will be used to compare OS between two treatment groups. Hazard ratio with confidence interval will be estimated based on Cox proportional hazard model. The Cox proportional hazard model will be used for multivariate analysis.
measure
Overall Survival
time Frame
Up to 5 years
description
Rates of Receiving 5FUCMT: For selective group patients, the proportion of patients who received 1) pre-operative 5FUCMT, 2) post-operative 5FUCMT, 3) either pre or post-operative 5FUCMT, and confidence intervals (according to approach of Duffy and Santner) will be reported.
measure
Rates of Receiving Pre- or Post-operative 5FUCMT
time Frame
Up to 5 years
description
Time to Local Recurrence (TLR): The distribution of TLR by group will be estimated using the method of Kaplan-Meier. 5 year local recurrence free rates by treatment group with confidence intervals based on Kaplan-Meier curves will be reported. The comparison of the cumulative incidence of local recurrence between groups, treating distant recurrence and death as competing risks using the test of Gray (Annals of Statistics, 1988) will be conducted.
measure
Local Recurrence (TLR):
time Frame
Up to 5 years
description
neoadjuvant rectal (NAR) score =\[5 \* pN - 3(cT - pT) + 12\]\^2/9.61. cT is an element of the set {1, 2, 3, 4}, pT is in {0, 1, 2, 3, 4}, and pN is in {0, 1, 2}. cT clinical tumor stage, pT pathologic tumor stage, pN pathologic nodal stage. Low (NAR \<8), intermediate (NAR = 8-16), and high (NAR \>16). Low is better and high is worse.
measure
Neoadjuvant Rectal Score
time Frame
Up to 5 years

Full study description

brief Summary: The standard treatment for locally advanced rectal cancer involves chemotherapy and radiation, known as 5FUCMT, (the chemotherapy drugs 5-fluorouracil/capecitabine and radiation therapy) prior to surgery. Although radiation therapy to the pelvis has been a standard and important part of treatment for rectal cancer and has been shown to decrease the risk of the cancer coming back in the same area in the pelvis, some patients experience undesirable side effects from the radiation and there have been important advances in chemotherapy, surgery, and radiation which may be of benefit. The purpose of this study is to compare the effects, both good and bad, of the standard treatment of chemotherapy and radiation to chemotherapy using a combination regimen known as FOLFOX, (the drugs 5-fluorouracil (5-FU), oxaliplatin and leucovorin) and selective use of the standard treatment, depending on response to the FOLFOX. The drugs in the FOLFOX regimen are all FDA (Food and Drug Administration) approved and have been used routinely to treat patients with advanced colorectal cancer.
detailed Description: OUTLINE: This is a multicenter, phase II/III study. Patients are stratified according to ECOG performance status (0 or 1 vs 2) and randomized to 1 of 2 treatment regimens. Patients will receive full supportive care while on this study. OBJECTIVES: Primary 1. Phase II component: To assure that neoadjuvant FOLFOX followed by selective use of 5FUCMT group (Group 1) maintains the current high rate of pelvic R0 resection and is consistent with non-inferiority for time to local recurrence (TLR). 2. Phase III component: To compare neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) to standard 5FUCMT (Group 2) with respect to the primary endpoint of the Disease-Free Survival (DFS). Secondary 1. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard group 5FUCMT (Group 2) with respect to the proportion of patients who achieve a pathologic complete response (pCR) at the time of surgical resection. 2. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard 5FUCMT (Group 2) with respect to overall survival. 3. To evaluate and compare the adverse event profile and surgery complications between two groups. 4. To estimate the proportion of patients in the selective group (Group 1) who receive: 1) pre-operative 5FUCMT; 2) post-operative 5FUCMT; 3) either pre- or post-operative 5FUCMT. 5. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard 5FUCMT (Group 2) with respect to Local Recurrence (TLR) 6. To determine if the neoadjuvant FOLFOX followed by selective use of 5FUCMT (Group 1) is non-inferior to the standard 5FUCMT (Group 2) with respect to Neoadjuvant Response Score (NAR) Event monitoring of patients will continue up to 8 years post randomization.

Source references

references

citation
Zhang T, Shi L, Jian L, Jiang J, Qiu Y, Xie F, Zhang J, Peng H, Zhong L, Chen Y, Zhong Y, Deng Y; FOWARC Group. Clinical Benefit and Cost-Effectiveness of FOLFOX Versus LCCRT in Neoadjuvant Treatment for Patients with Locally Advanced Rectal Cancer: An Economic Analysis of the FOWARC and PROSPECT Trial. Ann Surg Oncol. 2026 May;33(5):3814-3826. doi: 10.1245/s10434-025-18802-8. Epub 2025 Dec 11.
pmid
41379261
type
DERIVED
citation
Felder S, Frakes J, George M, Rosen A, Sahin IH. Which Treatment for Which Patient: Rectal Cancer Management After PROSPECT Trial. Oncology (Williston Park). 2024 May 13;38(5):187-190. doi: 10.46883/2024.25921019.
pmid
38776515
type
DERIVED
citation
Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. doi: 10.1056/NEJMoa2303269. Epub 2023 Jun 4.
pmid
37272534
type
DERIVED
citation
Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. doi: 10.1200/JCO.23.00903. Epub 2023 Jun 4.
pmid
37270691
type
DERIVED
citation
Schrag D, Weiser M, Saltz L, Mamon H, Gollub M, Basch E, Venook A, Shi Q. Challenges and solutions in the design and execution of the PROSPECT Phase II/III neoadjuvant rectal cancer trial (NCCTG N1048/Alliance). Clin Trials. 2019 Apr;16(2):165-175. doi: 10.1177/1740774518824539. Epub 2019 Jan 28.
pmid
30688523
type
DERIVED