Capivasertib China PK Study

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT04742036

Collaborator

(none)

Enrollment

Location

Arm

17.1

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, 2-part Phase I study to assess the PK, safety and tolerability of capivasertib as monotherapy and in combination with paclitaxel in Chinese participants with advanced solid tumours

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumours	Drug: Capivasertib Drug: Paclitaxel	Phase 1

Detailed Description

A Phase I study is designed to assess the PK, safety and tolerability of single-dose and multiple-dose capivasertib as monotherapy (Part A) and in combination with paclitaxel (Part

in approximately 16 Chinese participants with advanced solid tumours and to detect any differences in the PK profile between Chinese and Caucasian participants due to ethnicity. Descriptive summary will be conducted on the PK analysis set and safety analysis set.The evaluation of capivasertib PK data will be based on the PK analysis set.The assessment on safety and tolerability will be based on the safety analysis set.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Open-label Study to Assess the Pharmacokinetics, Safety, and Tolerability of Capivasertib Monotherapy and in Combination With Paclitaxel in Chinese Patients With Advanced Solid Tumours.

Actual Study Start Date :

Feb 22, 2021

Actual Primary Completion Date :

Jul 29, 2022

Actual Study Completion Date :

Jul 29, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: capivasertib single-dose and multiple-dose capivasertib as monotherapy (Part A) and then in combination with paclitaxel (Part B)	Drug: Capivasertib Part A Cycle 0: Single dose 480 mg(3 x 160 mg tablets) on Day 1 of Cycle 0 Cycle 1 (monotherapy): 480 mg(3 x 160 mg tablets) twice daily given on an intermittent weekly dosing schedule (4 days on, 3 days off for 7 days) Part B Cycle 2 (in combination therapy with paclitaxel): 400 mg (2 x 200 mg tablets) twice daily given on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle. Capivasertib treatment will continue until disease progression, unacceptable toxicity or the participant requests to stop treatment. Other Names: AZD5363 Drug: Paclitaxel Part B Cycle 2: Patients will receive 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle. Paclitaxel treatment will continue for at least 6 cycles, unless the participant experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel, or disease progression.

Arm

Intervention/Treatment

Experimental: capivasertib

single-dose and multiple-dose capivasertib as monotherapy (Part A) and then in combination with paclitaxel (Part B)

Drug: Capivasertib

Part A Cycle 0: Single dose 480 mg(3 x 160 mg tablets) on Day 1 of Cycle 0 Cycle 1 (monotherapy): 480 mg(3 x 160 mg tablets) twice daily given on an intermittent weekly dosing schedule (4 days on, 3 days off for 7 days) Part B Cycle 2 (in combination therapy with paclitaxel): 400 mg (2 x 200 mg tablets) twice daily given on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle. Capivasertib treatment will continue until disease progression, unacceptable toxicity or the participant requests to stop treatment.

Other Names:

AZD5363

Drug: Paclitaxel

Part B Cycle 2: Patients will receive 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle. Paclitaxel treatment will continue for at least 6 cycles, unless the participant experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel, or disease progression.

Outcome Measures

Primary Outcome Measures

Area under the plasma concentration-time curve from time zero to 12 hours post-dose (AUC 0-12) of Capivasertib [first dose up to approximately 6 months]
AUC0-12 is defined as area under the curve from 0 to 12 hours.
Maximum plasma concentration (Cmax) of Capivasertib [first dose up to approximately 6 months]
Cmax is defined as maximum plasma concentration
terminal half-life (t1/2) of Capivasertib [first dose up to approximately 6 months]
t1/2 is defined as terminal half-life
Accumulation ratio (Rac) of Capivasertib [first dose up to approximately 6 months]
Rac is defined as accumulation ratio

Secondary Outcome Measures

Safety and tolerability of drugs by assessment of AEs/SAEs [From time of signature of the ICF, through study completion, up to 17 months, and including the 30-day follow-up period after discontinuation of study drug]
Graded according to the National Cancer Institute (NCI CTCAE V5.0)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key inclusion criteria

Participants must have at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computer tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements, or Lytic or mixed (lytic + sclerotic) bone lesions that can be assessed by CT or MRI 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.
Histologically or, where appropriate, cytologically-confirmed malignant solid tumour refractory or resistant to standard therapy and for which no suitable effective standard therapy exists
Participants must have a life expectancy of ≥12 weeks
Participants must be eligible for paclitaxel treatment as per local investigator assessment
ECOG performance status 0-1
Participants must be on a stable concomitant medication regimen, defined as no changes in medication or in dose within 2 weeks prior to start of capivasertib dosing, except for bisphosphonates, denosumab and corticosteroids, which should be stable for at least 4 weeks prior to start of capivasertib dosing

Key Exclusion criteria

Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment
Other malignancies within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
Participants with any ongoing toxicities (>CTCAE grade 2), with the exception of alopecia, caused by previous cancer therapy
Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
Any of the following cardiac criteria at screening:
Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive ECGs
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third-degree heart block)
Clinically significant abnormalities of glucose metabolism as defined by any of the following at screening:
Participants with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment
glycosylated haemoglobin (HbA1c) ≥8.0% (63.9 mmol/mol)
Inadequate bone marrow reserve or organ function
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
Refractory nausea and vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib
Previous allogeneic bone marrow transplant or solid organ transplant
Evidence of dementia-altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent
Any previous treatment with AKT, PI3K, and/or mTOR inhibitors
Participation in another clinical study with an IP administered in the last 30 days or 5 half-lives, whichever is longer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Shanghai		China	200032

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator: Xichun Hu, Department of Medical Oncology, Fudan University Shanghai Cancer Center
Principal Investigator: Jian Zhang, Department of Medical Oncology, Fudan University Shanghai Cancer Center