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Status unknownNCT03280407NEOLARUpdated Sep 28, 2017

NEOadjuvant Chemotherapy Only Compared With Standard Treatment for Locally Advanced Rectal Cancer

A Phase 2 interventional study of Capecitabine and FOLFOX regimen (oxaliplatin/leucovorin/5FU) in Colorectal Neoplasm, Colorectal Cancer and Rectal Neoplasms, sponsored by Zealand University Hospital. Status unknown at 1 site in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-28.

Sponsored by Zealand University Hospital · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Sep 2017), so the status shown — last known as Recruiting — may be out of date.
Phase
Phase 2
Study type
Interventional
Enrollment
124
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The main clinical hypothesis is that compared to radio-chemotherapy for low and mid rectal tumors or surgery for high rectal tumors neoadjuvant chemotherapy reduces the rate of distant relapse without increasing the rate of local relapse.

The aim of the present study is to compare long term and short term outcomes in rectal cancer patients undergoing standard treatment (radio-chemotherapy/surgery) or experimental neoadjuvant chemotherapy/surgery Furthermore, early surgical and medical complications, the functional outcome, toxicity and quality of life (QoL) may be improved if radiotherapy can be avoided.

Exploratory analyses are planned in order to find potential predictive markers for selecting patients to either radio-chemotherapy/surgery or neoadjuvant combination chemotherapy/surgery.

Read the detailed description

The standard treatment of locally advanced but resectable cancer in the middle or lower rectum is preoperative radio-chemotherapy and in the upper part initial surgery. The clinical benefit from radio-chemotherapy is primarily through a reduction in local relapse but the treatment is associated with acute toxicity and long term functional dysfunction. Subsequently, it is important to select patients with high risk of local relapse. Intense systemic combination chemotherapy reduces the risk of distant relapse and increases survival in the postoperative setting. The biological rationale is eradication of micrometastases and hence it may be anticipated that earlier, i.e. neoadjuvant, combination therapy may improve systemic control.

02

Conditions studied

  • Colorectal Neoplasm
  • Colorectal Cancer
  • Rectal Neoplasms
  • Chemotherapy Effect
  • Intestinal Disease
  • Intestinal Neoplasms
  • Rectal Cancer

Keywords

  • Neoadjuvant chemotherapy,
  • locally advanced rectal cancer,
  • chemotherapy
  • CAPOX (oxaliplatin/capecitabine)
  • FOLFOX (oxaliplatin/leucovorin/5FU)
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Adenocarcinoma of the rectum with the lower boarder within 15 cm from the anal verge
  • Locally advanced tumor based on imaging
  • T3 tumors within 10 cm from the anal verge fulfilling the criteria for preoperative radio-chemotherapy according to Danish Colorectal Cancer Group (DCCG) guidelines
  • T3c or T4 tumors 10-15 cm from the anal verge
  • Deemed resectable at the multidisciplinary team (MDT) conference
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Age at least 18 years
  • Adequate bone marrow, liver and renal function allowing systemic chemotherapy
  • Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l.
  • Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal value
  • Calculated or measured renal glomerular filtration rate at least 30 mL/min
  • Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable
  • Written and orally informed consent

Exclusion criteria

Exclusion Criteria:

  • Distant metastasis
  • Invasive ingrowth into other organs
  • Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
  • Previous radiotherapy to the pelvis
  • Previous treatment with 5FU or oxaliplatin
  • Surgery within two weeks
  • Neuropathy NCI grade > 1
  • Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri
  • Pregnant (positive pregnancy test) or breast feeding women
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
124 participants (estimated)

Study arms

  • Active comparator
    A, capecitabine

    Radiochemotherapy with 50.4 Gy in 28 fractions concomitantly with chemotherapy

    Drug: Capecitabine

  • Experimental
    B, FOLFOX or CAPOX

    Neoadjuvant chemotherapy with CAPOX (oxaliplatin/capecitabine) or FOLFOX regimen (oxaliplatin/leucovorin/5FU), according to institutional practice

    Drug: FOLFOX regimen (oxaliplatin/leucovorin/5FU) · Drug: CAPOX (oxaliplatin/capecitabine)

Interventions

  • DrugCapecitabine

    Radio-chemotherapy with 50.4 Gy in 28 fractions to tumor and regional lymph nodes concomitantly with capecitabine 825 mg/m2 b.i.d

  • DrugFOLFOX regimen (oxaliplatin/leucovorin/5FU)

    Six cycles: Oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every two weeks.

    Also known as: FOLFOX (oxaliplatin/leucovorin/5FU)

  • DrugCAPOX (oxaliplatin/capecitabine)

    Four cycles: Oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks.

05

What researchers measure

Primary outcomes

  1. Disease free survival

    All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually until the number of events is reached and the trial is stopped (max 5 years)

    Time frame: 5 years

Secondary outcomes

  1. Overall survival

    All patients will be evaluated with CT and MRI scans and clinically every 6 months for 2 years and annually for maximum 5 years

    Time frame: 5 years

  2. Local relapse

    Defined to be within the pelvis. Any relapse should be verified by biopsy

    Time frame: 5 years

  3. Distant relapse

    Defined to be outside the pelvis. Any relapse should be verified by biopsy

    Time frame: 5 years

  4. Early toxicity

    Evaluated using CTCEA (Common Terminology Criteria for Adverse Events) version 4.

    Time frame: 5 years

  5. Late toxicity

    Evaluated using CTCEA version 4.

    Time frame: 5 years

  6. Functional outcome

    Measured with LARS questionnaire

    Time frame: 5 years

  7. Quality of life (QoL)

    Measured with EORTC QoL questionnaire

    Time frame: 5 years

06

Study locations

1 of 1 sites recruiting
07

References and documents

Individual participant data

Plan to share: Undecided — Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03280407
Lead sponsor
Zealand University Hospital
Responsible party
Ismail Gögenur (Professor, Zealand University Hospital) — Principal investigator
First posted
Sep 12, 2017
Start date
Mar 1, 2017
Primary completion
Dec 31, 2018 (estimated)
Completion
Dec 31, 2024 (estimated)
Last update
Sep 28, 2017

Study contacts

Ismail Gögenur, MD
Contact
igo@regionsjaelland.dk
+45 26336426
Lars Henrik Jensen, MD
Contact
Ismail Gögenur, MD
study chair · Department of Surgery, ZUH
Lars Henrik Jensen, MD
principal investigator · Vejle Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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