Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

PAKT: AZD5363 in Combination With Paclitaxel in Triple-Negative Advanced or Metastatic Breast Cancer (PAKT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02423603
Recruitment Status : Active, not recruiting
First Posted : April 22, 2015
Last Update Posted : February 25, 2020
Sponsor:
Collaborators:
AstraZeneca
Cancer Research UK
Information provided by (Responsible Party):
Queen Mary University of London

Brief Summary:

PAKT was an investigator-led, placebo-controlled, randomized phase II trial performed in 42 academic medical centers in the United Kindom, South Korea, France, Hungary, Romania, and Georgia. Patients were randomly assigned (1:1) to receive paclitaxel plus capivasertib or paclitaxel plus placebo. Stratification was by number of metastatic sites (< 3 v ≥ 3) and interval from the end of prior adjuvant or neoadjuvant chemotherapy (≤ 12 v > 12 months v no prior chemotherapy).

Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Capivasertib 400 mg or placebo was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle. All treatments were continued until disease progression, development of unacceptable toxicity, or withdrawal of consent. If paclitaxel treatment was discontinued before disease progression, patients could continue to receive capivasertib or placebo alone. In case of adverse events (AEs), capivasertib or placebo could be reduced to 320 mg twice per day and subsequently to 240 mg twice per day. Capivasertib or placebo could be interrupted for up to 4 weeks for toxicity.

Tumor assessments included computed tomography scanning or magnetic resonance imaging of the chest, abdomen, and pelvis at baseline, every 8 weeks during treatment, and at progression. Patients who discontinued treatment for any reason other than progression were required to follow the same schedule of assessments until progression, initiation of another treatment, death, or withdrawal of consent.


Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Paclitaxel Drug: AZD5363 Drug: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Double-blind, Randomised, Placebo-controlled Study of the AKT Inhibitor AZD5363 in Combination With Paclitaxel in Triple-Negative Advanced or Metastatic Breast Cancer (PAKT).
Actual Study Start Date : May 2014
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Arm Intervention/treatment
Active Comparator: Paclitaxel + AZD5363
Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Capivasertib 400 mg was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle.
Drug: Paclitaxel
Patient receive Once a week for three weeks - with one week off treatment
Other Name: Taxol

Drug: AZD5363
Patients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information.
Other Name: Capivasertib

Placebo Comparator: Paclitaxel + Placebo
Paclitaxel was administered as a once-per-week intravenous infusion of 90 mg/m2 over approximately 1 hour on days 1, 8, and 15 of each 28-day treatment cycle. Placebo was administered orally twice per day on an intermittent weekly dosing schedule, with treatment on days 2 to 5 of weeks 1, 2, and 3 within each 28-day cycle.
Drug: Paclitaxel
Patient receive Once a week for three weeks - with one week off treatment
Other Name: Taxol

Drug: Placebo
Patients receive AZD5363/Placebo in an intermittent treatment schedule. Please see study arms for full information.




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: Date of randomisation to date of first tumour progression or death (this can range on average between 3 weeks and 32 weeks). ]
    Progression-free survival, defined as the time from the date of randomisation to the date of first documented tumour progression (using RECIST 1.1) or death from any cause, whichever occurs first.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent prior to admission to this study
  2. Women, age > 18 years
  3. Histologically confirmed breast cancer
  4. Metastatic or locally recurrent disease; locally recurrent disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
  5. Patient must have

    • At least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥15mm) with CT, or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements, OR
    • lytic or mixed bone lesions in the absence of measurable disease as defined above; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible.
  6. Radiological or clinical evidence of recurrence or progression
  7. Triple-negative disease
  8. Formalin fixed paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing
  9. Patients must be able to swallow and retain oral medication
  10. Haematologic and biochemical indices within protocol specified ranges
  11. ECOG performance status 0-2
  12. Non-childbearing potential. If patient is of childbearing potential, she must have a negative serum pregnancy test and agree to use adequate contraception
  13. Willing and able to provide written informed consent

Exclusion Criteria:

  1. Patients with confirm brain metastases or a history of primary central nervous system tumours or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.
  2. Prior chemotherapy for metastatic breast cancer
  3. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study medication
  4. Prior treatment with PI3K inhibitors, AKT inhibitors or mTOR inhibitors
  5. Prior treatment with paclitaxel or docetaxel in the (neo)adjuvant setting within 12 months from inclusion into this study
  6. Pre-existing sensory or motor polyneuropathy ≥ Grade 2 according to CTCAE
  7. Malabsorption syndrome or other condition that would interfere with enteral absorption
  8. Clinically significant pulmonary dysfunction
  9. Prolongation defined as a QTc interval >470msecs or other significant abnormalities in rhythm, conduction or morphology of resting ECG including 2nd degree (Type II) or 3rd degree AV block or bradycardia (ventricular rate <50 beats/min)
  10. Any factors that increase risk of QTc prolongation or risk of arrythmic events
  11. Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade ≥2, or cardiac ejection fraction outside institutional range of normal or <50%
  12. Clinically significant abnormalities of glucose metabolism
  13. Patients with proteinuria or creatine >1.5xULN concurrent with creatinine clearance <50mL/min
  14. Exposure to potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2D6 within 2 weeks before the first dose of study treatment
  15. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry
  16. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
  17. Detained persons or prisoners
  18. Pregnant or nursing women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423603


Locations
Show Show 46 study locations
Sponsors and Collaborators
Queen Mary University of London
AstraZeneca
Cancer Research UK
Investigators
Layout table for investigator information
Study Chair: Peter Schmid Queen Mary University London
Principal Investigator: Nicholas Turner Royal Marsden Hospital NHS- Institute of Cancer Research
Publications of Results:
Layout table for additonal information
Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT02423603    
Other Study ID Numbers: 009246QM
2013-001521-43 ( EudraCT Number )
First Posted: April 22, 2015    Key Record Dates
Last Update Posted: February 25, 2020
Last Verified: February 2020
Keywords provided by Queen Mary University of London:
Triple Negative Breast Cancer
Metastatic
AKT Inhibitor
Advanced
AZD5363
Paclitaxel
PAKT
Capivasertib
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action