Docetaxel With or Without AZD6244 in Melanoma (DOC-MEK)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01256359
First received: November 17, 2010
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

This is a randomised, double-blind placebo controlled phase 2 trial. Patient will be randomly assigned 1:1 between 2 treatment arms. They will receive either docetaxel 75mg/m2 IV and placebo given bd, or AZD6244 75mg bd daily with docetaxel 75mg/m2 IV. Docetaxel will be administered every 3 weeks for a maximum 6 cycles, but AZD6244/placebo may be continued beyond this, until disease progression. The objective is to assess whether the combination of AZD6244 with docetaxel is worthy of evaluation in a definitive randomised study, with the null hypothesis being that the combination has activity similar to that of docetaxel alone in this population. After consent has been obtained mutational analysis of tumour BRAF will be performed on archival tumour tissue, where this information is not already known, to assess eligibility for the study. If there is no archival tissue a fresh biopsy will be requested from the patient. A blood sample will also be taken for future genetic analysis. Once taking part in the trial patients will need to attend their oncology unit regularly for monitoring and the delivery of treatment. Patients will undergo complete physical examination at screening, on C1D1, C1D8, C1D15, C2D1, C2D8 and day 1 of every subsequent cycle. Blood for haematology, biochemistry and clotting will be taken at each of these visits. A 12 lead ECG will be performed at screening . Disease assessment will be by CT scanning using modified RECIST criteria after 9 and 18 weeks, then every 3 months until disease progression.


Condition Intervention Phase
Melanoma
Drug: Docetaxel and AZD6244
Drug: Docetaxel and placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind Randomised Phase 2 Trial of Docetaxel With or Without AZD6244 in wt BRAF Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: Analysis will be performed when approximately 58 disease progression/death events have occurred. Average time 7 months. ] [ Designated as safety issue: No ]
    To assess the efficacy of AZD6244 in combination with docetaxel, compared with docetaxel alone, in first line patients with wild type BRAF advanced malignant melanoma


Estimated Enrollment: 80
Study Start Date: October 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Docetaxel and AZD6244
Docetaxel with AZD6244
Drug: Docetaxel and AZD6244
Docetaxel 75mg/m2 IV and AZD6244 75mg bd daily. Docetaxel will be administered every 3 weeks for a maximum 6 cycles, but AZD6244 may be continued beyond this, until disease progression.
Other Name: Taxotere
Experimental: Docetaxel and Placebo
Docetaxel without AZD6244
Drug: Docetaxel and placebo
Docetaxel 75mg/m2 IV and placebo given bd. Docetaxel will be administered every 3 weeks for a maximum 6 cycles, but placebo may be continued beyond this, until disease progression.
Other Name: Taxotere

Detailed Description:

No further information in addition to what has been provided in the brief summary

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged >/= 16 years
  • Able to provide evidence from an accredited laboratory of wt BRAF status for their melanoma, or ascertainment of wt BRAF status from a sample of melanoma provided for mutational analysis in Oxford.
  • Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma
  • At least 1 lesion, not previously irradiated, that can be accurately measured on CT or MRI as defined by modified RECIST criteria
  • ECOG performance score of 0 or 1.
  • Life expectancy of at least 12 weeks.
  • The patient is willing to give consent to the main study and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.
  • Haematological and biochemical indices within the ranges shown below. Lab Test Value required Haemoglobin (Hb) >10g/dL White Blood Count (WBC) > 3x109/L Platelet count > 100,000/μL Absolute Neutrophil count > 1.5x109/L; Serum bilirubin ≤ 1.2 x ULN AST (SGOT) or ALT ≤ 2.5 x ULN LDH ≤ 2 x ULN Creatinine clearance (Cockcroft-Gault) >50 ml/min

Exclusion Criteria:

  • Any anti-cancer therapy (including radiotherapy and participation in other clinical trials) within 28 days prior to Day 1.
  • Prior DNA damaging agents or cytotoxic chemotherapy for metastatic melanoma.
  • Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade 2.
  • Pregnancy or breastfeeding women. Female patients must have a negative urinary or serum pregnancy test or have evidence of post-menopausal status (defined as absence of menstruation for > 12 months, bilateral oophrectomy or hysterectomy).
  • Grade ≥2 peripheral neuropathy at study entry.
  • Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients)
  • Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80
  • Ocular or mucosal malignant melanoma
  • Another active malignancy within the past five years.
  • Evidence of brain metastases, unless surgically resected/stereotactic radiosurgery treated brain metastasis with no evidence of relapse on cerebral MRI, or treated brain metastasis and stable off treatment, including steroids, for 3 months.
  • Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis.
  • Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
  • Cardiac conditions, including uncontrolled hypertension (BP>160/100 despite treatment), heart failure NYHA class 2 or above, prior or current cardiomyopathy, myocardial infarction within 6 months or angina requiring nitrate therapy more than once a week.
  • Previous treatment with EGFR, ras, raf or MEK inhibitors.
  • Inability to swallow capsules, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption.
  • Taking medication that significantly induces or inhibits CYP3A4.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01256359

Locations
United Kingdom
Churchill Hospital
Oxford, Oxfordshire, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Mark R Middleton University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01256359     History of Changes
Other Study ID Numbers: OCTO_015
Study First Received: November 17, 2010
Last Updated: November 12, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014