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Trial record 43 of 173 for:    pertuzumab

Testing the Addition of an Anti-cancer Drug, Copanlisib, to the Usual Maintenance Treatment (Trastuzumab and Pertuzumab) After Initial Chemotherapy in a Phase Ib/II Trial for Advanced HER2 Positive Breast Cancer

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ClinicalTrials.gov Identifier: NCT04108858
Recruitment Status : Not yet recruiting
First Posted : September 30, 2019
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase Ib/II trial studies the side effects and best dose of copanlisib when given together with trastuzumab and pertuzumab and to see how well ithey work after induction treatment in treating patients with HER2 positive stage IV breast cancer with PIK3CA or PTEN mutation. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Trastuzumab is a form of "targeted therapy" because it works by attaching itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Monoclonal antibodies, such as pertuzumab, may kill tumor cells that are left after chemotherapy. The addition of copanlisib to the usual treatment (trastuzumab and pertuzumab) could shrink the cancer or stabilize it for longer duration as compared to the usual treatment alone.

Condition or disease Intervention/treatment Phase
Anatomic Stage IV Breast Cancer AJCC v8 ERBB2 Gene Amplification HER2 Positive Breast Carcinoma Metastatic Breast Carcinoma PIK3CA Gene Mutation PTEN Gene Mutation Drug: Copanlisib Biological: Pertuzumab Biological: Trastuzumab Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib/II Trial of Copanlisib in Combination With Trastuzumab and Pertuzumab After Induction Treatment of HER2 Positive (HER2+) Metastatic Breast Cancer (MBC) With PIK3CA Mutation or PTEN Mutation
Estimated Study Start Date : December 6, 2019
Estimated Primary Completion Date : November 30, 2021
Estimated Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Phase I, Phase II Arm I (copanlisib, trastuzumab, pertuzumab)
Patients receive copanlisib IV over 60 minutes on days 1 and 8. Patients also receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Copanlisib
Given IV
Other Names:
  • BAY 80-6946
  • PI3K Inhibitor BAY 80-6946

Biological: Pertuzumab
Given IV
Other Names:
  • 2C4
  • 2C4 Antibody
  • MoAb 2C4
  • Monoclonal Antibody 2C4
  • Omnitarg
  • Perjeta
  • rhuMAb2C4
  • RO4368451

Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • ALT02
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • Herzuma
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • Ogivri
  • Ontruzant
  • PF-05280014
  • rhuMAb HER2
  • RO0452317
  • SB3
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar ALT02
  • trastuzumab biosimilar EG12014
  • Trastuzumab Biosimilar HLX02
  • Trastuzumab Biosimilar PF-05280014
  • Trastuzumab Biosimilar SB3
  • Trastuzumab-dkst
  • Trastuzumab-dttb
  • Trastuzumab-pkrb
  • Trastuzumab-QYYP
  • Trazimera

Active Comparator: Phase II Arm II (trastuzumab, pertuzumab)
Patients receive trastuzumab IV over 30-90 minutes and pertuzumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: Pertuzumab
Given IV
Other Names:
  • 2C4
  • 2C4 Antibody
  • MoAb 2C4
  • Monoclonal Antibody 2C4
  • Omnitarg
  • Perjeta
  • rhuMAb2C4
  • RO4368451

Biological: Trastuzumab
Given IV
Other Names:
  • ABP 980
  • ALT02
  • Anti-c-ERB-2
  • Anti-c-erbB2 Monoclonal Antibody
  • Anti-ERB-2
  • Anti-erbB-2
  • Anti-erbB2 Monoclonal Antibody
  • Anti-HER2/c-erbB2 Monoclonal Antibody
  • Anti-p185-HER2
  • c-erb-2 Monoclonal Antibody
  • HER2 Monoclonal Antibody
  • Herceptin
  • Herceptin Biosimilar PF-05280014
  • Herceptin Trastuzumab Biosimilar PF-05280014
  • Herzuma
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • Ogivri
  • Ontruzant
  • PF-05280014
  • rhuMAb HER2
  • RO0452317
  • SB3
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar ALT02
  • trastuzumab biosimilar EG12014
  • Trastuzumab Biosimilar HLX02
  • Trastuzumab Biosimilar PF-05280014
  • Trastuzumab Biosimilar SB3
  • Trastuzumab-dkst
  • Trastuzumab-dttb
  • Trastuzumab-pkrb
  • Trastuzumab-QYYP
  • Trazimera




Primary Outcome Measures :
  1. Incidence of adverse events and serious adverse events (Phase Ib) [ Time Frame: Up to 3 months ]
    The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for adverse event (AE) reporting.

  2. Incidence of dose limiting toxicities (DLTs) (Phase Ib) [ Time Frame: Up to 3 months ]
    Will measure the incidence of DLTs to determine recommended phase 2 dose. Will tabulate the toxicity data by grade, severity and dose level.

  3. Progression-free survival (PFS) (Phase II) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 months ]
    The statistical test for the primary analysis will be the partial likelihood ratio test of a stratified Cox PH model with treatment group as a covariate.


Secondary Outcome Measures :
  1. PFS (Phase Ib) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 months ]
  2. Overall survival (OS) (Phase Ib) [ Time Frame: Up to 3 months ]
    Will use the Kaplan-Meier method to estimate OS.

  3. OS (Phase II) [ Time Frame: Up to 3 months ]
    Will use the Kaplan-Meier method to estimate OS.

  4. Incidence of adverse events and serious adverse events (Phase II) [ Time Frame: Up to 3 months ]
    The descriptions and grading scales found in the revised NCI CTCAE version 5.0 will be utilized for AE reporting.


Other Outcome Measures:
  1. Number of induction cycles (Phase II) [ Time Frame: Up to 3 months ]
    Will correlate PFS and OS with number of induction cycles. Will assess the extent to which treatment effects (measured as hazard ratio for time to progression and odds ratio for response) depend on number of induction cycles (using product terms in logistic and Cox PH regression models).

  2. Hormone receptor (HR) status (estrogen receptor [ER] and progesterone receptor [PR]) (Phase II) [ Time Frame: Up to 3 months ]
    Will correlate PFS and OS with hormone receptor status (ER and PR). Will assess the extent to which treatment effects (measured as hazard ratio for time to progression and odds ratio for response) depend on HR status (using product terms in logistic and Cox PH regression models).

  3. Molecular alteration analysis (Phase II) [ Time Frame: Up to 3 months ]
    Will correlate PFS and OS with molecular alterations identified through whole exome sequencing and ribonucleic acid sequencing in tumor tissue, as well as circulating tumor deoxyribonucleic acid analysis.

  4. Change in expression of pharmacodynamics markers downstream of PI3K inhibition (Phase II) [ Time Frame: Baseline up to 3 months ]
    Will correlate PFS and OS with change in expression of pharmacodynamics markers downstream of PI3K inhibition.

  5. Change in expression of genes involved in alternate signaling pathways identified through reverse phase protein array (RPPA) (Phase II) [ Time Frame: Baseline up to 3 months ]
    Will correlate PFS and OS with change in expression of genes involved in alternate signaling pathways identified through RPPA.



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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:

  • PHASE IB/SAFETY RUN-IN ONLY: Molecular biomarker selection will not be mandated
  • PHASE IB/SAFETY RUN-IN ONLY: Patients will be enrolled after completion of induction chemotherapy with any taxane, trastuzumab and pertuzumab; or after progression on any prior treatment. The last dose of prior treatment should be at least 3 weeks before the start of the trial
  • PHASE II ONLY: Presence of actionable mutation in either PIK3CA gene or PTEN gene on molecular testing, in primary or metastatic tumor at Clinical Laboratory Improvement Act (CLIA) certified laboratory. Results of molecular testing will be reviewed to confirm eligibility by MD Anderson Precision Oncology Decision Support team and captured in patient's record
  • PHASE II ONLY: Patients must be within 8 weeks of completion of first-line induction chemotherapy (i.e., 4-8 cycles of any taxane, trastuzumab and pertuzumab) without evidence of progression. Patients may receive up to 2 doses of HER2 targeted treatment between end of induction treatment and start of trial, while eligibility is being confirmed
  • Clinical stage IV as assessed by American Joint Committee on Cancer (AJCC) (8th edition, anatomic staging) guidelines with known metastatic disease (Edge and Compton, 2010; Amin et al., 2017)
  • HER2+ breast cancer as assessed by the American Society of Clinical Oncology (ASCO)-College of American Pathologists (ASCO-CAP) guidelines (Wolff et al., 2013; Wolff et al., 2018). HER2 testing of metastasis will be required. Positive HER2 test result is defined as:

    • IHC 3+ based on circumferential membrane staining that is complete, intense
    • In situ hybridization (ISH) positive based on:

      • Single-probe average HER2 copy number >= 6.0 signals/cell
      • Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number >= 4.0 signals/cell
      • Dual-probe HER2/CEP17 ratio >= 2.0 with an average HER2 copy number < 4.0 signals/cell unless HER2 by immunohistochemistry (IHC) is 2+ or less
      • Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL
  • Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram or multigated acquisition scan (MUGA)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 x ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN OR =< 5 x ULN for subjects with liver metastases
  • Creatinine =< 1.5 x institutional ULN OR measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]). Creatinine clearance should be calculated per institutional standard
  • International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulation as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulation as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Patients with treated brain metastases are eligible if follow-up brain imaging 30 days after central nervous system (CNS)-directed therapy shows no evidence of progression
  • Patients who are therapeutically treated with anticoagulation including warfarin will be allowed to participate provided that their medication dose and INR/PTT is stable. Due to interaction of copanlisib with warfarin, patients who are on warfarin should be monitored closely while on this trial
  • Women of child-bearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior tubal ligation (>= 1 year before screening), total hysterectomy or menopause (defined as 12 consecutive months of amenorrhea). Patients should not become pregnant or breastfeed while on this study
  • Patients and their partners, if sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 7 months after last dose of study drug(s) to prevent pregnancy in the study patient or partner
  • Hormone receptor positive breast cancer patients will be allowed to continue endocrine therapy as indicated while participating in this clinical trial
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Known active hepatitis B or hepatitis C infection. All patients must be screened for hepatitis B virus (HBV) and hepatitis C virus (HCV) up to 28 days prior to study drug start using the routine hepatitis virus lab panel. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on non-CYP3A4-interactive suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV RNA
  • Human immunodeficiency virus (HIV)-positive patients, unless they have CD4 counts > 500 cells/mm^3 in the past 6 months and do not require CYP3A4-interactive antiretroviral therapy
  • Active infection requiring IV antibiotics or other uncontrolled intercurrent illness requiring hospitalization
  • Inability to comply with the study and follow-up procedures
  • History of cerebrovascular accident (CVA), myocardial infarction, symptomatic congestive heart failure, cardiac arrhythmia, or unstable angina within the previous 6 months before starting therapy
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the following exceptions: alopecia (any grade is acceptable); neuropathy must have resolved to =< grade 2. Congestive heart failure (CHF) due to prior anti-cancer therapy must have been =< grade 1 in severity at the time of occurrence, and must have resolved completely
  • Current uncontrolled hypertension (>= 150/90)
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Patients with uncontrolled type I or II diabetes mellitus (DM); uncontrolled DM is defined as glycosylated hemoglobin (HbA1c) > 8.5% and a fasting blood glucose of > 120 mg/dL within 14 days prior to trial entry
  • Immunosuppressive therapy is not allowed while on study
  • Patients who are receiving any other investigational agents
  • Patients with leptomeningeal disease or active untreated brain metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to copanlisib, PI3K inhibitors, or HER2 inhibitors
  • Copanlisib is primarily metabolized by CYP3A4. Therefore, the concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) are not permitted from 14 days prior to enrollment until the end of the study. Other medications that are prohibited while on copanlisib treatment:

    • Herbal medications/preparations (except for vitamins)
    • Anti-arrhythmic therapy other than beta blockers or digoxin
    • Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Systemic corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not permitted while on study. Previous corticosteroid therapy must be stopped or reduced to the allowed dose at least 7 days prior to the computed tomography (CT)/magnetic resonance imaging (MRI) screening. If a patient is on chronic corticosteroid therapy, corticosteroids should be de-escalated to the maximum allowed dose before the screening. Patients may be using topical or inhaled corticosteroids
  • Patients with non-healing wound, ulcer, or bone fracture
  • Pregnant women are excluded from this study because copanlisib is a PI3K inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with copanlisib, breastfeeding should be discontinued if the mother is treated with copanlisib. These potential risks may also apply to other agents used in this study

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): NCT04108858


Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Rashmi Murthy University of Texas MD Anderson Cancer Center LAO

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04108858     History of Changes
Other Study ID Numbers: NCI-2019-06461
NCI-2019-06461 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10296 ( Other Identifier: University of Texas MD Anderson Cancer Center LAO )
10296 ( Other Identifier: CTEP )
UM1CA186688 ( U.S. NIH Grant/Contract )
First Posted: September 30, 2019    Key Record Dates
Last Update Posted: November 19, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm

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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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Pertuzumab
Carcinoma
Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents