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Trial record 23 of 49 for:    rucaparib

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.

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ClinicalTrials.gov Identifier: NCT03840200
Recruitment Status : Recruiting
First Posted : February 15, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Breast Cancer Prostate Cancer Ovarian Cancer Drug: Part 1, Dose Level 1 and Dose Level 2a: Ipatasertib Drug: Part 1, Dose level 2b and dose level 3: Ipatasertib Drug: Part 1, Dose Level 1 and Dose Level 2b: Rucaparib Drug: Part 1, Dose Level 2a and Dose Level 3: Rucaparib Phase 1 Phase 2

Detailed Description:

There are two parts in the study. 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

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 11, 2019
Estimated Primary Completion Date : September 24, 2021
Estimated Study Completion Date : November 5, 2021


Arm Intervention/treatment
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
Drug: 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.
Other Name: RO5532961, GDC-0068

Drug: 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.
Other Name: RO5532961, GDC-0068

Drug: 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.
Other Name: CO-338

Drug: 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.
Other Name: CO-338

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).
Drug: 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.
Other Name: RO5532961, GDC-0068

Drug: 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.
Other Name: RO5532961, GDC-0068

Drug: 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.
Other Name: CO-338

Drug: 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.
Other Name: CO-338




Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 3 years ]
  2. Percentage of Participants with Dose-Limiting Toxicities (DLTs) that Determine the Maximum-Tolerated Dose (MTD) of the Ipatasertib and Rucaparib Combination [ Time Frame: Day -7 to Day 28 of Cycle 1; 1 cycle = 28 days ]
  3. Percentage of Participants with Prostate-Specific Antigen (PSA) Response [ Time Frame: 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 Measures :
  1. 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) [ Time Frame: 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) ]
  2. Duration of Objective Response in Participants with Measurable Disease at Baseline, as Assessed by Investigator Based on RECIST v1.1 [ Time Frame: 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) ]
  3. Radiographic Progression Free Survival, as Assessed by Prostate Cancer Working Group 3 Criteria [ Time Frame: 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) ]
  4. Overall Survival in All Participants [ Time Frame: Baseline up to disease progression or death due to any cause whichever occurs first (up to approximately 3 years) ]
  5. Plasma Concentration of Ipatasertib [ Time Frame: Day -7, 1, 15 of Cycle 1, Day 1, 15 of Cycle 2 (1 cyce = 28 days) ]
  6. Plasma Concentration of Ipatasertib's Metabolite, G-037720 [ Time Frame: Day -7, 1, 15 of Cycle 1, Day 1, 15 of Cycle 2 (1 cycle = 28 days) ]
  7. Plasma Concentration of Rucaparib [ Time Frame: Day -7, 1, 15 of Cycle 1, Day 1, 15 of Cycle 2 (1 cycle = 28 days) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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 Exclusion Criteria:

  • 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

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): NCT03840200


Contacts
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Contact: Reference Study ID Number: BO40933 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
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United States, California
California Cancer Associates for Research & Excellence, Inc. Recruiting
Encinitas, California, United States, 92008
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Australia, New South Wales
Kinghorn Cancer Centre; St Vincents Hospital Recruiting
Darlinghurst, New South Wales, Australia, 2010
Macquarie University Hospital Recruiting
Sydney, New South Wales, Australia, 2109
Australia, Victoria
Cabrini Hospital Malvern Recruiting
Malvern, Victoria, Australia, 3144
Italy
Istituto Nazionale Tumori Regina Elena IRCCS Recruiting
Roma, Lazio, Italy, 00144
Fondazione IRCCS Istituto Nazionale dei Tumori; S. C. Oncologia Medica 2 Not yet recruiting
Milano, Lombardia, Italy, 20133
Azienda Ospedaliera Santa Maria di Terni Not yet recruiting
Terni, Umbria, Italy, 20089
Istituto Oncologico Veneto IRCCS Not yet recruiting
Padova, Veneto, Italy, 35128
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 03080
Severance Hospital, Yonsei University Recruiting
Seoul, Korea, Republic of, 03722
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 6351
Spain
Clínica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31620
Vall d´Hebron Institute of Oncology (VHIO), Barcelona Recruiting
Barcelona, Spain, 08035
Hospital Universitario Virgen de la Victoria Not yet recruiting
Malaga, Spain, 29010
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03840200     History of Changes
Other Study ID Numbers: BO40933
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Rucaparib
Prostatic Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents