Docetaxel With or Without AZD6244 in Melanoma | NCT01256359

NCT01256359

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Label	Type	Description	Intervention Names
Docetaxel and AZD6244	Experimental	Docetaxel with AZD6244	Drug: Docetaxel and AZD6244
Docetaxel and Placebo	Experimental	Docetaxel without AZD6244	Drug: Docetaxel and placebo

Name	Type	Description	Arm Group Labels	Other Names
Docetaxel and AZD6244	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression Free Survival	This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST (v1.1) criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.	From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.

Secondary Outcomes

Measure	Description	Time Frame
Progression Free Survival Rate at 6 Months	PFS at 6 months is defined as the percentage progression free survival at 6 months from the PFS Kaplan Meier graph. This would allow all patients randomised to be included. progression was diagnosed using CT scan, x-ray, MRI scan and clinical examination using modified RECIST(v1.1) criteria.	From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.

Other Outcomes

Measure	Description	Time Frame
Progression Free Survival: Sensitivity Analysis 1	Same as for primary analysis. This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST v1.1 criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.

Eligibility Module

Eligibility 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.

Name	Affiliation	Role
Mark R Middleton	University of Oxford	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Churchill Hospital		Oxford	Oxfordshire	OX3 7LJ	United Kingdom

Arm/Group Information

ID	Title	Description
FG000	Docetaxel and AZD6244	Docetaxel with AZD6244 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.
FG001	Docetaxel and Placebo	Docetaxel without AZD6244 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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Docetaxel and AZD6244	Docetaxel with AZD6244 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.
BG001	Docetaxel and Placebo

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression Free Survival

This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST (v1.1) criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.

The primary analysis was intention to treat and involved all patients who were randomly assigned.

Posted

Median

90% Confidence Interval

months

From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.

ID	Title	Description
OG000	Docetaxel and AZD6244	Docetaxel with AZD6244 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Docetaxel and AZD6244	Docetaxel with AZD6244 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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 29, 2014	Nov 18, 2020	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Feb 28, 2013	Feb 25, 2021	SAP_001.pdf

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type

ID	Term
D000077143	Docetaxel
C517975	AZD 6244

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic