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A Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Breast Cancer Research Foundation
Geron Corporation
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01265927
First received: December 3, 2010
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

A study to evaluate safety and biologic effects of giving GRN163L in combination with trastuzumab in patients diagnosed with HER2+ metastatic breast cancer that is resistant to therapy with trastuzumab.


Condition Intervention Phase
Breast Neoplasms
Drug: GRN163L in combination with trastuzumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Inhibiting Telomerase to Reverse Trastuzumab Resistance in HER2+ Breast Cancer

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Determine the dose-limiting toxicity of GRN163L in combination with trastuzumab in patients with refractory HER2+ metastatic disease [ Time Frame: End of Study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Measure the concentration of trastuzumab and GRN163L from blood samples immediately before and after infusion on day 1, weekly during cycle 1, and immediately prior to cycle 2 [ Time Frame: Until cycle 2 ] [ Designated as safety issue: No ]
    PK data will be described using means, standard deviations, medians, minimums and maximums.

  • Tumor biopsy and bone marrow aspirate assayed for telomerase activity prior to treatment and immediately prior to planned cycle 2 [ Time Frame: Until cycle 2 ] [ Designated as safety issue: No ]
    Telomerase activity data will be described using means, standard deviations, medians, minimums and maximums.

  • Flow cytometry to compare cell cycle distribution in tumor and bone marrow prior to treatment and immediately prior to cycle 2. [ Time Frame: Until cycle 2 ] [ Designated as safety issue: No ]
    Marrow (and tumor when sufficient sample is available) will be analyzed via flow cytometry to determine cell distribution. Percentage of cells at each cycle will be described using means, standard deviations, medians, minimums and maximums.

  • Tumor samples analyzed for activation of HER2 family signaling protein activation (phosphorylation) status prior to treatment and immediately prior to cycle 2. [ Time Frame: Until cycle 2 ] [ Designated as safety issue: No ]
    HER2 family signaling protein activation will be described using means, standard deviations, medians, minimums and maximums.

  • Determine objective response rate (ORR) and progression free survival (PFS) of GRN163L in combination with trastuzumab in this patient population [ Time Frame: End of Study ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: January 2011
Estimated Study Completion Date: August 2016
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GRN163L + Trastuzumab Drug: GRN163L in combination with trastuzumab
GRN163L will be administered in escalating dose cohorts on Day 1 of each 21-day cycle prior to trastuzumab infusion. Trastuzumab will be a administered day 1 of each 21-day cycle after GRN163L. There will be a 30 minute observation period between the end of the GRN163L infusion and the beginning of the trastuzumab infusion.
Other Names:
  • Imetelstat Sodium
  • Herceptin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females 18 years or older at the time of consent.
  2. ECOG performance status of 0-2 within 21 days of study registration.
  3. Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. NOTE: locally recurrent disease must not be amenable to surgery or radiation with curative intent.
  4. Measurable or evaluable disease according to RECIST v1.1 within 35 days prior to study registration.
  5. Disease must be amenable to biopsy (image-guided or via direct visualization of superficial lesions) with minimal risk to the patient. NOTE: Patients with disease limited to the lung and/or pleura are excluded.
  6. Disease must be HER2+ as defined by IHC 3+ or FISH ratio > 2.0.
  7. Resistant to trastuzumab as defined as (1) progression within 12 months of completing adjuvant/neoadjuvant trastuzumab or (2) progression on trastuzumab administered for metastatic disease.
  8. Prior treatment with lapatinib or investigational HER2 targeted therapies is allowed but not required. There are no limits on the number of regimens or other prior anti-HER2 therapies patients have received.
  9. LVEF ≥ Lower Limit of Normal based on MUGA or ECHO within 35 days prior to study registration
  10. Females of childbearing potential and males must be willing to use an effective method of contraception from the time consent is signed until 6 months after treatment discontinuation. Methods of contraception include hormonal birth control (oral contraceptives, patch, injection, vaginal ring or implant), two barrier methods of birth control, abstinence and/or other methods as determined by the treating physician.
  11. Females of childbearing potential must have a negative pregnancy test within 14 days prior to registration for protocol therapy.

    NOTE: Females are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (> 12 months since last menses).

    Laboratory values must be obtained within 21 days of study registration:

  12. Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
  13. Platelets ≥ 100 K/mm3
  14. Hemoglobin (Hgb) ≥ 9.0 g/dL (may be transfused)
  15. Serum creatinine < 3.0 mg/dL
  16. Total Bilirubin ≤ 1.5 x ULN
  17. AST/SGOT ≤ 2.5 x ULN. If liver metastases is present, AST ≤ 5 x ULN
  18. ALT, SGPT ≤ 2.5 x ULN. If liver metastases is present, ALT ≤ 5 x ULN

    Exclusion Criteria:

  19. No Investigational therapy within 4 weeks of study registration
  20. No hormonal therapy within 2 weeks of study registration
  21. No cytotoxic chemotherapy within 2 weeks of study registration.
  22. No prior treatment with GRN163L
  23. No prior history of severe reaction to trastuzumab, as determined by the treating physician.
  24. No history of clinically significant cardiac dysfunction, including:

    Current uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg), or unstable angina History of symptomatic CHF (Grade >3 by NCI CTCAE or Class >II by NYHA criteria [see Appendix IV]) or serious cardiac arrhythmia requiring treatment within 12 months of study registration, with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia History of myocardial infarction within 6 months of study registration

  25. No history of cerebrovascular accident within 12 months of study registration
  26. No active CNS metastases. Patients with previously treated CNS metastases who do not require chronic steroids or anticonvulsants are eligible.
  27. Prior radiation therapy must not have involved > 25% of bone marrow due to potential myelosuppression with GRN163L. See bone marrow chart in Appendix III

    NOTE: Radiation therapy within 2 weeks of study registration is not allowed.

  28. Females must not be breastfeeding.
  29. No clinically significant active infection, as determined by the treating physician
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01265927

Locations
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Breast Cancer Research Foundation
Geron Corporation
Investigators
Principal Investigator: Kathy Miller, MD Indiana University
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01265927     History of Changes
Other Study ID Numbers: IUCRO-0314, 1010-05
Study First Received: December 3, 2010
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
Breast Cancer
Breast Tumors
Cancer of Breast
Cancer of the Breast
Genes, HER-2
Genes, HER2

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Trastuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014