Induction Chemotherapy Plus Chemoradiation as First Line Treatment for Locally Advanced Cervical Cancer (INTERLACE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University College, London
Sponsor:
Collaborator:
Cancer Research UK
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01566240
First received: March 27, 2012
Last updated: August 12, 2013
Last verified: August 2013
  Purpose

Chemoradiation has been the standard treatment for advanced cervical cancer for a decade, but one third of women still die from a failure to control systemic disease. In a recent multicentre phase II trial of 46 women the investigators found that, 68% of women had tumours that responded to weekly induction chemotherapy prior to chemoradiation. The induction chemotherapy had acceptable toxicity and did not compromise the standard chemoradiation treatment. In addition, the overall survival and progression free survival at 3 years was 66% (95% CI 4779). These results, together with acceptable toxicity, provide justification for evaluating induction chemotherapy prior to chemoradiation in a randomised phase III trial. The investigators aim to investigate in a randomised trial whether additional induction chemotherapy given on a weekly schedule immediately before standard chemoradiation leads to an improvement in overall survival. The investigators plan to recruit 770 women with locally advanced cervical cancer who are eligible for standard chemoradiation, they will be randomised to weekly carboplatin and paclitaxel chemotherapy for 6 weeks followed by chemoradiation or to chemoradiation alone. The trial will recruit for 4 years with 5 years of follow up period.


Condition Intervention Phase
Cervical Cancer
Drug: Paclitaxel
Drug: Carboplatin
Radiation: Radiotherapy
Drug: Cisplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Multicentre Trial of Weekly Induction Chemotherapy Followed by Standard Chemoradiation Versus Standard Chemoradiation Alone in Patients With Locally Advanced Cervical Cancer

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: 12 weeks post treatment and then as required ] [ Designated as safety issue: No ]
  • Adverse events (AE) as assessed by the Common Terminology Criteria for Adverse Events v4.03 [ Time Frame: To be assessed at every timepoint i.e. baseline; at every chemotherapy cycle, at all follow up visits. ] [ Designated as safety issue: Yes ]
  • Quality of Life (UK and Ireland only) as assessed by EORTC QLQ-C30, QLQ-CX24 and EQ-5D [ Time Frame: Baseline, during induction chemotherapy (Week 4), day 1 of chemoradiation, during chemoradiation (Weeks 3), 4 weeks post end of treatment, and as part of follow up (3 monthly for 2 years; 6 monthly for 3 years until 5 years post randomisation) ] [ Designated as safety issue: No ]
  • Patterns of first relapse (local and/or systemic) [ Time Frame: 12 weeks post treatment and as required ] [ Designated as safety issue: No ]

Estimated Enrollment: 770
Study Start Date: September 2012
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chemoradiation
Radiotherapy (external beam and brachytherapy) plus concurrent Cisplatin weekly for 5 weeks
Radiation: Radiotherapy
Radiotherapy comprising external beam 40-50.4Gy in 20-28 fractions plus intracavity brachytherapy to achieve a minimum total EQD2 dose of 78-86Gy.
Drug: Cisplatin
Cisplatin 40 mg/m2 (capped at 70mg total dose) weekly for five weeks maximum, commencing in the first week of radiotherapy or as soon as blood counts have recovered from induction chemotherapy.
Experimental: Induction Chemotherapy + Chemoradiation
6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator
Drug: Paclitaxel
Paclitaxel 80 mg/m2 (capped at 160mg maximum total dose) weekly for 6 weeks i.e. on days 1, 8, 15, 22, 29 & 36.
Drug: Carboplatin
Carboplatin AUC 2 (capped at 270mg maximum total dose) weekly for 6 weeks i.e. on day 1, 8, 15, 22, 29, & 36.
Radiation: Radiotherapy
Radiotherapy comprising external beam 40-50.4Gy in 20-28 fractions plus intracavity brachytherapy to achieve a minimum total EQD2 dose of 78-86Gy.
Drug: Cisplatin
Cisplatin 40 mg/m2 (capped at 70mg total dose) weekly for five weeks maximum, commencing in the first week of radiotherapy or as soon as blood counts have recovered from induction chemotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed FIGO stage Ib2-IVa squamous, adeno or adenosquamous carcinoma of the cervix (except FIGO IIIA)
  • Deemed suitable and fit for radical chemoradiation
  • Medically fit to receive carboplatin and paclitaxel
  • ECOG performance status 0 - 1
  • No evidence of active TB
  • Aged 18 and over
  • Adequate renal function, defined as a GFR ≥ 60 ml/min calculated using the Wright equation (or ≥ 50 ml/min for radioisotope GFR assessment)
  • Adequate liver function, as defined by ALT or AST < 2.5 ULN and bilirubin < 1.25 ULN
  • Adequate bone marrow function as defined by ANC ≥1.5 x 109/L, platelets ≥ 100 x 109/L
  • Using adequate contraception precautions if relevant
  • A documented negative HIV test (patients recruited from high risk countries or who have moved within the past 10 years from high risk countries)
  • A documented negative pregnancy test (if applicable)
  • Capable of providing written or witnessed informed consent

Patients with positive (pelvic/para-aortic/both) nodes (either histologically/PET positive ≥15 mm on CT/MRI) at or below the level of the aortic bifurcation may be included in the study provided none of the exclusion criteria apply.

Exclusion Criteria:

  • Previous pelvic malignancy (regardless of interval since diagnosis)
  • Previous malignancy not affecting the pelvis (except basal cell carcinoma of the skin) where disease free interval is less than 10 years
  • Positive lymph nodes (imaging or histological) above the aortic bifurcation*
  • Involvement of lower 1/3 vagina (FIGO IIIA disease)
  • Hydronephrosis which has not undergone ureteric stenting or nephrostomy except where the affected kidney is non-functioning
  • Evidence of distant metastasis i.e. any non-nodal metastasis beyond the pelvis
  • Previous pelvic radiotherapy
  • Prior diagnosis of Crohn's disease or Ulcerative colitis
  • Uncontrolled cardiac disease (defined as cardiac function which would preclude hydration during cisplatin administration and any contraindication to paclitaxel)
  • Pregnant or lactating * i.e. PET any size, CT/MRI ≥ 15mm
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566240

Contacts
Contact: Jaymi Patel +44 207 679 9866 j.patel@ctc.ucl.ac.uk

Locations
United Kingdom
North Devon District Hospital Recruiting
Barnstaple, Devon, United Kingdom, EX31 4JB
Principal Investigator: Jennifer Forrest         
University College London Hospital Recruiting
London, Greater London, United Kingdom, NW1 2BU
Principal Investigator: Mary McCormack         
Weston Park Hospital Not yet recruiting
Sheffield, South Yorkshire, United Kingdom, S10 2SJ
Principal Investigator: Simon Pledge         
Royal Devon and Exeter NHS Foundation Trust Recruiting
Exeter, United Kingdom, EX2 5DY
Principal Investigator: Jennifer Forrest         
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Susan Davidson         
Nottingham University Hospitals NHS Trust Not yet recruiting
Nottingham, United Kingdom, NG5 1PB
Principal Investigator: Anjana Anand         
Sponsors and Collaborators
University College, London
Cancer Research UK
Investigators
Principal Investigator: Mary Dr McCormack, MBBS, FRCR University College London Hospitals NHS Foundation Trust
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01566240     History of Changes
Other Study ID Numbers: UCL 11/0034, 2011-001300-35, C37815/A12832
Study First Received: March 27, 2012
Last Updated: August 12, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by University College, London:
cervical cancer
Chemotherapy
Paclitaxel
Carboplatin
Cisplatin
Radiotherapy
Chemoradiation
Brachytherapy
Stage IB2 Cervical Cancer
Stage IIA Cervical Cancer
Stage IIB Cervical Cancer
Stage IIIB Cervical Cancer
Stage IVA Cervical Cancer

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Cisplatin
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 26, 2014