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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03840200




Registration number
NCT03840200
Ethics application status
Date submitted
11/02/2019
Date registered
15/02/2019
Date last updated
8/08/2019

Titles & IDs
Public title
A Study Evaluating the Safety, Pharmacokinetics and Efficacy of Ipatasertib Administered in Combination With Rucaparib in Participants With Advanced Breast, Ovarian Cancer, and Prostate Cancer.
Scientific title
A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Ipatasertib in Combination With Rucaparib in Patients With Advanced Breast, Ovarian, or Prostate Cancer
Secondary ID [1] 0 0
BO40933
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Prostate Cancer 0 0
Ovarian Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Ovarian and primary peritoneal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Part 1, Dose Level 1 and Dose Level 2a: Ipatasertib
Treatment: Drugs - Part 1, Dose level 2b and dose level 3: Ipatasertib
Treatment: Drugs - Part 1, Dose Level 1 and Dose Level 2b: Rucaparib
Treatment: Drugs - Part 1, Dose Level 2a and Dose Level 3: Rucaparib

Experimental: Ipatasertib + Rucaparib - A Dose-Escalation Phase (Part 1) in participants with previously treated advanced breast cancer, ovarian cancer, or prostate cancer. There will be a 7-day run-in period with ipatasertib alone prior to Cycle 1, Day 1. After the completion of the ipatasertib run-in period, participants will begin Cycle 1, Day 1 of the ipatasertib and rucaparib combination treatment. Each cycle has 28 days. Participants will be split into 4 cohorts: Dose Level 1 group - 300 mg ipatasertib once daily (QD) + 400 mg rucaparib twice daily (BID), Dose Level 2a: 300 mg ipatasertib QD + 600 mg rucaparib BID, Dose Level 2b: 400 mg ipatasertib QD + 400 mg rucaparib BID, Dose Level 3: 400 mg ipatasertib QD + 600 mg rucaparib BID

Experimental: Part 2: Ipatasertib + Rucaparib - A Dose-Expansion Phase (Part 2) - The recommended dose identified in Part 1 (highest dose level of ipatasertib and rucaparib with an acceptable safety profile and less than one-third of participants experience a dose limiting toxicity) will be evaluated in participants with advanced prostate cancer who have had at least one line of prior therapy with second-generation androgen-receptor (AR)-targeted agents (e.g., abiraterone, enzalutamide, apalutamide).


Treatment: Drugs: Part 1, Dose Level 1 and Dose Level 2a: Ipatasertib
Ipatasertib, 300 mg administered PO QD for 7 days (run-in period prior to Cycle 1), then administer 300 mg PO QD for each cycle. Each cycle has 28 days. Doses are administered until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Treatment: Drugs: Part 1, Dose level 2b and dose level 3: Ipatasertib
Ipatasertib, 400 mg administered PO QD for 7 days (run-in period prior to Cycle 1), then administer 400 mg PO QD for each cycle. One cycle has 28 days. Doses are administered until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Treatment: Drugs: Part 1, Dose Level 1 and Dose Level 2b: Rucaparib
Rucaparib is administered 400 mg twice daily (BID) for each cycle. One cycle has 28 days. Doses are administered until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Treatment: Drugs: Part 1, Dose Level 2a and Dose Level 3: Rucaparib
Rucaparib is administered 600 mg twice daily (BID) for each cycle. One cycle has 28 days. Doses are administered until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Adverse Events
Timepoint [1] 0 0
Baseline up to approximately 3 years
Primary outcome [2] 0 0
Percentage of Participants with Dose-Limiting Toxicities (DLTs) that Determine the Maximum-Tolerated Dose (MTD) of the Ipatasertib and Rucaparib Combination
Timepoint [2] 0 0
Day -7 to Day 28 of Cycle 1; 1 cycle = 28 days
Primary outcome [3] 0 0
Percentage of Participants with Prostate-Specific Antigen (PSA) Response
Timepoint [3] 0 0
At screening (<=28 days of first dose), Day 1 of Cycle 1, 2, 3 and >= 4, at treatment discontinuation and post-treatment follow-up (1 cycle = 28 days; baseline up to approximately 3 years)
Secondary outcome [1] 0 0
Percentage of Participants with Objective Response, as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1)
Timepoint [1] 0 0
At end of Cycle 2, 4, 6 and every 3 cycles thereafter up to progression (1 cycle = 28 days; baseline up to approximately 3 years)
Secondary outcome [2] 0 0
Duration of Objective Response in Participants with Measurable Disease at Baseline, as Assessed by Investigator Based on RECIST v1.1
Timepoint [2] 0 0
At end of Cycle 2, 4, 6 and every 3 cycles thereafter up to progression (1 cycle = 28 days; baseline up to approximately 3 years)
Secondary outcome [3] 0 0
Radiographic Progression Free Survival, as Assessed by Prostate Cancer Working Group 3 Criteria
Timepoint [3] 0 0
At end of Cycle 2, 4, 6 and every 3 cycles thereafter up to radiographic progression (1 cycle = 28 days; baseline up to approximately 3 years)
Secondary outcome [4] 0 0
Overall Survival in All Participants
Timepoint [4] 0 0
Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 3 years)
Secondary outcome [5] 0 0
Plasma Concentration of Ipatasertib
Timepoint [5] 0 0
Day -7, 1, 15 of Cycle 1, Day 1, 15 of Cycle 2 (1 cyce = 28 days)
Secondary outcome [6] 0 0
Plasma Concentration of Ipatasertib's Metabolite, G-037720
Timepoint [6] 0 0
Day -7, 1, 15 of Cycle 1, Day 1, 15 of Cycle 2 (1 cycle = 28 days)
Secondary outcome [7] 0 0
Plasma Concentration of Rucaparib
Timepoint [7] 0 0
Day -7, 1, 15 of Cycle 1, Day 1, 15 of Cycle 2 (1 cycle = 28 days)

Eligibility
Key inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- A life expectancy of at least 3 months

- Ability to swallow oral study drug

- Have adequate organ and marrow function as confirmed by the laboratory values listed
below, obtained within 28 days prior to the first dose of study treatment:

- Bone marrow function assessments (without transfusion within 28 days prior to receipt
of study treatment):

1. ANC >= 1500 cells/uL (1.5 x 10^9/L) without granulocyte-colony stimulating factor
support

2. Platelet count >= 100.0 x 10^9/L

3. Hemoglobin >= 9 g/dL (or 5.6 mmol/L)

- Chemistry panel assessments:

1. AST and ALT <= 1.5 x upper limit of normal (ULN); if liver metastases, <= 2.5 x
ULN

2. Bilirubin <= 1.5 x ULN (<= 3 x ULN if hyperbilirubinemia is due to Gilbert's
syndrome)

3. Serum albumin >= 3.0 g/dL

4. Serum creatinine <= 1.5 x ULN or creatinine clearance >= 50 mL/min

5. Fasting glucose <= 150 mg/dL and hemoglobin A1c <= 7.5%

- Resolved or stabilized toxicities resulting from previous therapy to Grade 1 (except
for alopecia and neuropathy).

Cancer-Related Inclusion Criteria

- Have a histologically confirmed diagnosis of ovarian (Part 1 only), breast (Part 1
only) or prostate cancer (Part 1 and Part 2)

- Disease must be either metastatic or locally advanced disease that cannot be treated
with curative intent

- For patients with ovarian cancer (Part 1 only):

1. High-grade (2 or 3) serous or endometrioid or clear cell epithelial ovarian,
fallopian tube, or primary peritoneal cancer (PPC)

2. Must have received at least one prior platinum-based therapy and may have
platinumsensitive disease (i.e., documented radiologic disease progression >= 6
months following the last dose of the platinum treatment administered) or
platinum-resistant disease

3. Have a CA-125 level that is > 2 x ULN

4. Must have measurable disease by RECIST v1.1

- For patients with breast cancer (Part 1 only): must be human epidermal growth factor
receptor 2 negative (HER2-) (estrogen receptor [ER]/progesterone positive or
negative):

1. ER/progesterone-positive patients must have received and progressed on at least
one endocrine therapy (adjuvant or metastatic)

2. ER/progesterone-negative/HER2- (triple-negative breast cancer [TNBC]) patients
must have received at least one prior line of chemotherapy for metastatic breast
cancer

3. Must not have received more than two prior lines of chemotherapy for metastatic
breast cancer

4. Must have measurable disease by RECIST v1.1

For patients with prostate cancer:

1. Adenocarcinoma of the prostate without small cell or neuroendocrine features

2. Surgical or medical castration with testosterone < 50 ng/dL (1.7 nM)

3. Patients treated with luteinizing hormone-releasing hormone analogs must have
initiated therapy at least 4 weeks prior to the first dose of study treatment and
continue throughout the study treatment

4. Progression of prostate cancer either via PSA progression (two rising PSA levels
measured >= 1 week apart, with second result >= 1 ng/mL) or radiographic progression
with or without PSA progression

5. Must have received at least one prior line of second-generation androgen receptor
targeted therapy (e.g., abiraterone, enzalutamide, apalutamide)

6. Patients with prostate cancer must have either measurable disease by RECIST v1.1 or
bone lesions by bone scan, or both.

- Submission of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or a
minimum of 12 freshly cut, unstained, serial tumor slides from the most recently
collected tumor tissue for central molecular analysis (retrospective NGS testing
for HR and PI3K-AKT pathway status and for other protocol-mandated secondary and
exploratory assessments). Cytologic or fine needle aspirate samples are not
acceptable. Tumor tissue from bone metastases is not acceptable.

- For men and women of child bearing potential: agreement to remain abstinent or
use protocol defined contraceptive measures during the treatment period and for
at least 28 days after the last dose of ipatasertib,or 6 months after the last
dose of rucaparib, whichever occurs later
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant or breastfeeding, or intending to become pregnant during the study or within
28 days after the final dose of ipatasertib or 6 months after the final dose of
rucaparib

- Prior treatment with a PARP inhibitor, AKT inhibitor, or PI3K inhibitor

- Treatment with investigational therapy within 14 days prior to initiation of study
drug

- Symptomatic and/or untreated CNS metastases

- Uncontrolled tumor-related pain

- Non-study-related minor surgical procedures <= 5 days or major (invasive) surgical
procedure <=14 days prior to first dose of study treatment

- Patients with active hepatitis C virus (HCV)

- Hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive
hepatitis B surface antigen (HBsAg) test or a positive quantitative HBV DNA test

- Known HIV infection

- Illicit drug or alcohol abuse within 12 months prior to screening, in the
investigator's judgment

- Malabsorption syndrome or other condition that would interfere with enteral absorption

- Serious infection requiring antibiotics within 14 days of first dose of study
treatment

- Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator's judgment, precludes the patient's safe participation in and completion
of the study

- Need for chronic corticosteroid therapy of >= 10 mg of prednisone per day or an
equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a
chronic disease

- History of another malignancy within 5 years prior to randomization, except for either
adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma
in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder
(Tis, Ta, and low-grade T1 tumors), or other malignancies where the patient has
undergone potentially curative therapy with no evidence of disease and are deemed by
the treating physician to have a recurrence rate of < 5% at 5 years.

- History of clinically significant cardiovascular dysfunction

- Presence of any other condition that may have increased the risk associated with study
participation or may have interfered with the interpretation of study results, and, in
the opinion of the investigator, would have made the patient inappropriate for entry
into the study

Ipatasertib-Specific

- Type 1 or Type 2 diabetes mellitus requiring insulin at study entry

- History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis),
active bowel inflammation (e.g., diverticulitis)

- Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 4 weeks or five
elimination half-live of the inhibitors, whichever is longer, prior to initiation of
study drug

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Kinghorn Cancer Centre; St Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [3] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2109 - Sydney
Recruitment postcode(s) [3] 0 0
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Pennsylvania
Country [2] 0 0
Italy
State/province [2] 0 0
Lazio
Country [3] 0 0
Italy
State/province [3] 0 0
Lombardia
Country [4] 0 0
Italy
State/province [4] 0 0
Umbria
Country [5] 0 0
Italy
State/province [5] 0 0
Veneto
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Seoul
Country [7] 0 0
Spain
State/province [7] 0 0
Navarra
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Malaga

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a study in participants with advanced breast, ovarian, or prostate cancer to
investigate the dose, safety, pharmacokinetics, and preliminary efficacy of ipatasertib in
combination with rucaparib. The study consists of two parts: a Dose-Escalation Phase (Part 1)
in participants with previously treated advanced breast cancer, ovarian cancer, or prostate
cancer and a Dose-Expansion Phase (Part 2) in participants with advanced prostate cancer who
have had at least one line of prior therapy with second-generation androgen-receptor
(AR)-targeted agents (e.g., abiraterone, enzalutamide, apalutamide).
Trial website
https://clinicaltrials.gov/show/NCT03840200
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: BO40933 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global.rochegenentechtrials@roche.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03840200