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

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ClinicalTrials.gov Identifier: NCT01515787
Recruitment Status : Active, not recruiting
First Posted : January 24, 2012
Last Update Posted : June 10, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Canadian Cancer Trials Group
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE January 18, 2012
First Posted Date  ICMJE January 24, 2012
Last Update Posted Date June 10, 2019
Actual Study Start Date  ICMJE January 2012
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2015)
  • Pelvic R0 resection rate (Phase II) [ Time Frame: Up to 8 years ]
  • DFS (Phase III) [ Time Frame: Up to 8 years ]
  • Time to local recurrence (TLR) [ Time Frame: Up to 8 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
  • Pelvic R0 resection rate (Phase II)
  • DFS (Phase III)
  • Time to local recurrence (TLR)
Change History Complete list of historical versions of study NCT01515787 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2015)
  • Pathologic complete response [ Time Frame: Up to 8 years ]
  • Overall survival [ Time Frame: Up to 8 years ]
  • Adverse event (AE) profiles [ Time Frame: Up to 8 years ]
  • Rates of receiving pre- or post-operative 5FUCMT [ Time Frame: Up to 8 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2012)
  • Pathologic complete response
  • Overall survival
  • Adverse event (AE) profiles
  • Rates of receiving pre- or post-operative 5FUCMT
  • Bowel function between groups at 12 and 24 months
  • Sexual function, bladder function, and health-related quality-of-life between arms at 1 and 2 years
  • Correlation between MIP array copy number and mutational data with outcomes
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery
Official Title  ICMJE A Phase II/III Trial of Neoadjuvant FOLFOX With Selective Use of Combined Modality Chemoradiation Versus Preoperative Combined Modality Chemoradiation for Locally Advanced Rectal Cancer Patients Undergoing Low Anterior Resection With Total Mesorectal Excision (PROSPECT)
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 co-primary endpoints of the Time to Local Recurrence (TLR) and 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.

Event monitoring of patients will continue up to 8 years post randomization.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: FOLFOX (chemotherapy)
    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.
  • Other: 5 FUCMT (chemoradiation)
    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.
  • Procedure: surgery
    low anterior resection with total mesorectal excision
  • Procedure: magnetic resonance imaging or endorectal ultrasound
Study Arms  ICMJE
  • Experimental: Group 1

    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.

    Interventions:
    • Drug: FOLFOX (chemotherapy)
    • Other: 5 FUCMT (chemoradiation)
    • Procedure: surgery
    • Procedure: magnetic resonance imaging or endorectal ultrasound
  • Active Comparator: Group 2
    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.
    Interventions:
    • Drug: FOLFOX (chemotherapy)
    • Other: 5 FUCMT (chemoradiation)
    • Procedure: surgery
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 4, 2019)
1194
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2012)
1060
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Canada,   Israel,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01515787
Other Study ID Numbers  ICMJE N1048
CDR0000715321 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2012-00234 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
U10CA031946 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Canadian Cancer Trials Group
Investigators  ICMJE
Study Chair: Deborah Schrag, MD Dana-Farber Cancer Institute
PRS Account Alliance for Clinical Trials in Oncology
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP