Trial record 1 of 1 for:    N1048
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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.
Verified February 2013 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier:
NCT01515787
First received: January 18, 2012
Last updated: June 24, 2013
Last verified: February 2013

January 18, 2012
June 24, 2013
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

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether chemotherapy alone is more effective then chemotherapy plus radiation therapy in treating rectal cancer.

PURPOSE: This randomized phase II/III trial studies how well chemotherapy alone compared to chemotherapy plus radiation therapy works in treating patients with rectal cancer undergoing surgery.

OBJECTIVES:

Primary

  • To assure that neoadjuvant oxaliplatin, leucovorin calcium, and fluorouracil (FOLFOX) followed by selective use of combined modality therapy with fluorouracil (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). (Phase II)
  • To compare neoadjuvant FOLFOX followed by Selective use of 5FUCMT (Group 1) to standard 5FUCMT (Group 2) with respect to the proportion of patients who achieve a pathologic complete response (pCR) at the time of surgical resection. (Phase III)
  • To compare bowel function in patients randomized to the neoadjuvant FOLFOX followed by selective use of 5FUCMT vs standard 5FUCMT at approximately 1 and 2 years postoperatively.
  • To evaluate the feasibility of implementing the PRO-CTCAE in an NCI-sponsored treatment trial.
  • To evaluate the feasibility of implementing the PRO-CTCAE at Alliance sites.
  • To evaluate the feasibility of patients self-reporting symptoms during treatment by using the PRO-CTCAE.
  • To prospectively use Molecular Inversion Probe (MIP) array technology and MALDI-TOF mass spectrometry-based genotyping to identify copy number aberrations and somatic mutations that mediate tumor formation using formalin-fixed, paraffin-embedded (FFPE) tumor tissue from patients participating in the current study.
  • To determine whether germline genetic variants in candidate genes of interest are associated with response and/or toxicity to platinum and 5FU-based chemotherapy.

Secondary

  • 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 pCR at the time of surgical resection.
  • 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.
  • To evaluate and compare the adverse event profile and surgery complications between the two groups.
  • To estimate the proportion of patients in the selective group (Group 1) who receive pre-operative 5FUCMT, post-operative 5FUCMT, and either pre- or post-operative 5FUCMT.
  • To compare sexual function separately within men and within women between groups at approximately 1 and 2 years post-operatively.
  • To compare bladder function between groups at approximately 1 and 2 years post-operatively.
  • To compare health-related quality of life between groups at 1 and 2 years post-operatively.
  • To assess the correlation between bladder, bowel, and sexual function and quality of life. (Exploratory)
  • To investigate factors associated with bladder, bowel, and sexual dysfunction. (Exploratory)
  • To compare bladder and bowel function over time between genders. (Exploratory)
  • To perform subgroup analyses based on other sociodemographic factors. (Exploratory)
  • To evaluate and compare patients' self-reported symptom burden during treatment between groups using the PRO-CTCAE system.
  • To evaluate whether exposure to patient-reported symptoms influences CTCAE symptom reporting by research staff. (Exploratory)
  • To correlate the MIP array copy number and mutational data from patients with locally advanced rectal cancer with clinical outcome in each treatment cohort (the clinical outcomes include pathologic complete response, time to recurrence, time to pelvic recurrence, and overall survival).
  • To identify immune markers for response to neoadjuvant chemotherapy or chemoradiation using very well-established, validated immunologic assays.
  • To investigate the ability of neoadjuvant FOLFOX or chemoradiation to augment anti-tumor immunity against rectal cancer.
  • To identify novel immune targets in rectal cancer.
  • To determine whether germline genetic variants in candidate genes of interest are associated with response and/or toxicity to radiation therapy.
  • To assess whether genetic-risk variants identified in genome-wide association studies of colorectal cancer susceptibility are associated with rectal cancer clinical outcome and response to therapy.

OUTLINE: This is a multicenter, phase II study followed by a phase III study. Patients are stratified according to ECOG performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

  • Group 1 (FOLFOX): Patients receive neoadjuvant chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least 20% of tumor regression undergo low-anterior resection (LAR) with total mesorectal excision (TME). Patients with less than 20% of tumor regression undergo chemoradiation as in group 1 before proceeding to LAR with TME.
  • Group 2 (5FUCMT): Patients receive fluorouracil IV continuously 7 days a week for 5.5 weeks or capecitabine orally (PO) twice daily (BID) 5 days a week for 5.5 weeks. Patients also undergo 3-dimensional conformal or intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME.

Patients in both groups may receive adjuvant chemotherapy comprising FOLFOX and/or 5FUCMT.

Patients undergo blood sample collection at baseline and periodically during study for genotyping and immunologic studies. Paraffin-embedded tissue samples from primary tumor are also collected for aberration and somatic mutation studies by molecular inversion probe (MIP) array and mass spectrometry-based genotyping.

Patients complete the Bowel Function Index, the Prostate Health-Related Quality-of-Life (QOL) and the International Prostate Symptom Score (IPSS) questionnaires, the EuroQOL5D-5L (EQ5D) questionnaire, and the International Index of Erectile Function (IIEF) or Female Sexual Function Index (FSFI) questionnaire at baseline, and periodically during study.

After completion of study treatment, patient are followed up for up to 8 years.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Colorectal Cancer
  • Drug: capecitabine
    Given PO
  • Drug: fluorouracil
    Given IV
  • Drug: leucovorin calcium
    Given IV
  • Drug: oxaliplatin
    Given IV
  • Experimental: Group 1
    Patients receive neoadjuvant chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with at least 20% of tumor regression undergo low-anterior resection (LAR) with total mesorectal excision (TME). Patients with less than 20% of tumor regression undergo chemoradiation as in group 1 before proceeding to LAR with TME.
    Interventions:
    • Drug: fluorouracil
    • Drug: leucovorin calcium
    • Drug: oxaliplatin
  • Experimental: Group 2
    Patients receive fluorouracil IV continuously 7 days a week for 5.5 weeks or capecitabine orally (PO) twice daily (BID) 5 days a week for 5.5 weeks. Patients also undergo 3-dimensional conformal or intensity-modulated radiation therapy 5 days a week for approximately 5.5 weeks. Patients then undergo LAR with TME.
    Interventions:
    • Drug: capecitabine
    • Drug: fluorouracil
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)

DISEASE CHARACTERISTICS:

  • Diagnosis of rectal adenocarcinoma
  • Radiologically measurable or clinically evaluable disease
  • 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
  • Candidate for sphincter-sparing surgical resection prior to neoadjuvant therapy according to the primary surgeon

    • No patient for whom primary surgeon indicates need for abdominoperineal (APR) at baseline
  • Clinical stage T2N1, T3N0, T3N1 (stage IIA, IIIA, or IIIB)

    • 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 ≥ 10 mm
      • No clinical T4 tumors
  • Preoperative proctoscopy with tumor tissue evident between 5 and 12 cm from the anal verge, inclusive

    • No evidence that tumor is adjacent to (defined as within 3 mm of) the mesorectal fascia on pre-operative MRI or ERUS/pelvic CT scan
  • No tumor causing symptomatic bowel obstruction

PATIENT CHARACTERISTICS:

  • ECOG performance status 0, 1, or 2
  • Absolute neutrophil count (ANC) ≥ 1,500/mm³
  • Platelets ≥ 100,000/mm³
  • Hemoglobin > 8.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Patient of child-bearing potential is willing to employ adequate contraception
  • Willing to return to enrolling medical site for all study assessments
  • No other invasive malignancy ≤ 5 years prior to registration; exceptions are colonic polyps, non-melanoma skin cancer, or carcinoma-in-situ of the cervix
  • No co-morbid illnesses or other concurrent disease that, 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No chemotherapy within 5 years prior to registration (hormonal therapy is allowable if the disease-free interval is ≥ 5 years)
  • No prior pelvic radiation
Both
18 Years and older
No
Not Provided
United States
 
NCT01515787
N1048, NCCTG-N1048, CDR0000715321, NCI-2012-00234, U10CA031946
Yes
Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
North Central Cancer Treatment Group
National Cancer Institute (NCI)
Principal Investigator: Deborah Schrag, MD, MPH Memorial Sloan-Kettering Cancer Center
Alliance for Clinical Trials in Oncology
February 2013

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