Capivasertib China PK Study

NCT04742036 | Completed Phase 1

• 1 other identifier: D3614C00002
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Conditions

Advanced Solid Tumours

Keywords

Pharmacokinetics; Safety; Tolerability; Capivasertib; Chinese

Outcome Measures

Primary Outcomes (4)

• Area under the plasma concentration-time curve from time zero to 12 hours post-dose (AUC 0-12) of Capivasertib

  AUC0-12 is defined as area under the curve from 0 to 12 hours.

  first dose up to approximately 6 months

• Maximum plasma concentration (Cmax) of Capivasertib

  Cmax is defined as maximum plasma concentration

  first dose up to approximately 6 months

• terminal half-life (t1/2) of Capivasertib

  t1/2 is defined as terminal half-life

  first dose up to approximately 6 months

• Accumulation ratio (Rac) of Capivasertib

  Rac is defined as accumulation ratio

  first dose up to approximately 6 months

Secondary Outcomes (1)

• 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

Study Arms (1)

capivasertib

EXPERIMENTAL

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

Drug: Capivasertib; Drug: Paclitaxel

Interventions

Capivasertib DRUG

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.

Also known as: AZD5363

capivasertib

Paclitaxel DRUG

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.

capivasertib

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Shanghai, 200032, China

Location

Related Publications (1)

• Zhang J, Liu X, Du Y, Mu Y, Meng Y, Sun Y, Zhang L, Chen C, Cullberg M, Fan E, Hu X. A Phase I open-label study to assess the pharmacokinetics, safety, and tolerability of capivasertib alone or in combination with paclitaxel in Chinese patients with advanced solid tumors. BMC Cancer. 2025 Oct 14;25(1):1562. doi: 10.1186/s12885-025-14982-4.

  PMID: 41088025 DERIVED

MeSH Terms

Interventions

capivasertib; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Xichun Hu

  Department of Medical Oncology, Fudan University Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

• Jian Zhang

  Department of Medical Oncology, Fudan University Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2021
• First Posted: February 5, 2021
• Study Start: February 22, 2021
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: August 19, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

CN (1)