Trial record 1 of 6 for:    A Phase II/III Trial of Neoadjuvant FOLFOX
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Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01515787
First received: January 18, 2012
Last updated: August 28, 2014
Last verified: August 2014

January 18, 2012
August 28, 2014
January 2012
July 2017   (final data collection date for primary outcome measure)
  • Pelvic R0 resection rate (Phase II) [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • DFS (Phase III) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Time to local recurrence (TLR) [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Pelvic R0 resection rate (Phase II) [ Designated as safety issue: No ]
  • DFS (Phase III) [ Designated as safety issue: No ]
  • Time to local recurrence (TLR) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01515787 on ClinicalTrials.gov Archive Site
  • Pathologic complete response [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]
  • Adverse event (AE) profiles [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]
  • Rates of receiving pre- or post-operative 5FUCMT [ Time Frame: Up to 30 weeks ] [ Designated as safety issue: No ]
  • Pathologic complete response [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Adverse event (AE) profiles [ Designated as safety issue: Yes ]
  • Rates of receiving pre- or post-operative 5FUCMT [ Designated as safety issue: No ]
  • Bowel function between groups at 12 and 24 months [ Designated as safety issue: No ]
  • Sexual function, bladder function, and health-related quality-of-life between arms at 1 and 2 years [ Designated as safety issue: No ]
  • Correlation between MIP array copy number and mutational data with outcomes [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery
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

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Colorectal Cancer
  • 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
  • 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 shrunk in size by 20%, the patient will receive 5FUCMT (radiation with chemotherapy). If the tumor has decreased in size by at least 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 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. 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1060
Not Provided
July 2017   (final data collection date for primary outcome measure)

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. Clinical staging should be estimated based on the combination of the following assessments: physical exam by the primary surgeon, CT scan of the chest/abdomen/pelvis and either a pelvic MRI or an ultrasound (ERUS).

    Clinical stage N2 disease is to be estimated as four or more lymph nodes that are ≥ 10mm.

  9. Preoperative proctoscopy with distal end of tumor tissue evident between 5 and 12 cm from the anal verge, inclusive. Tumors should not extend below 5cm. Tumors may extend above 12 cm provided distal tumor is located between 5-12 cm.
  10. 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
  11. Negative pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
  12. Patient of child-bearing potential is willing to employ adequate contraception.
  13. Provide informed written consent
  14. 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 tumor is adjacent to (defined as within 3 mm of) the mesorectal fascia on pre-operative MRI or ERUS/pelvic CT scan.
  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 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.
Both
18 Years and older
No
United States
 
NCT01515787
N1048, NCCTG-N1048, CDR0000715321, NCI-2012-00234, U10CA031946
Yes
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Deborah Schrag, MD Dana-Farber Cancer Institute
Alliance for Clinical Trials in Oncology
August 2014

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