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

NCT01265927 | Completed Phase 1 DMC

• 2 other identifiers: IUCRO-03141010-05
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Neoplasms

Keywords

Breast Cancer; Breast Tumors; Cancer of Breast; Cancer of the Breast; Genes, HER-2; Genes, HER2

Outcome Measures

Primary Outcomes (1)

• Determine the dose-limiting toxicity of GRN163L in combination with trastuzumab in patients with refractory HER2+ metastatic disease

  End of Study

Secondary Outcomes (5)

• 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

  Until cycle 2

• Tumor biopsy and bone marrow aspirate assayed for telomerase activity prior to treatment and immediately prior to planned cycle 2

  Until cycle 2

• Flow cytometry to compare cell cycle distribution in tumor and bone marrow prior to treatment and immediately prior to cycle 2.

  Until cycle 2

• Tumor samples analyzed for activation of HER2 family signaling protein activation (phosphorylation) status prior to treatment and immediately prior to cycle 2.

  Until cycle 2

• Determine objective response rate (ORR) and progression free survival (PFS) of GRN163L in combination with trastuzumab in this patient population

  End of Study

Study Arms (1)

GRN163L + Trastuzumab

EXPERIMENTAL

Drug: GRN163L in combination with trastuzumab

Interventions

GRN163L in combination with trastuzumab DRUG

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.

Also known as: Imetelstat Sodium, Herceptin

GRN163L + Trastuzumab

Eligibility Criteria

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

You may qualify if:

• Males or females 18 years or older at the time of consent.
• ECOG performance status of 0-2 within 21 days of study registration.
• 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.
• Measurable or evaluable disease according to RECIST v1.1 within 35 days prior to study registration.
• 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.
• Disease must be HER2+ as defined by IHC 3+ or FISH ratio \> 2.0.
• 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.
• 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.
• LVEF ≥ Lower Limit of Normal based on MUGA or ECHO within 35 days prior to study registration
• 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.
• 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:
• Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
• Platelets ≥ 100 K/mm3

You may not qualify if:

• No Investigational therapy within 4 weeks of study registration
• No hormonal therapy within 2 weeks of study registration
• No cytotoxic chemotherapy within 2 weeks of study registration.
• No prior treatment with GRN163L
• No prior history of severe reaction to trastuzumab, as determined by the treating physician.
• 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
• No history of cerebrovascular accident within 12 months of study registration
• No active CNS metastases. Patients with previously treated CNS metastases who do not require chronic steroids or anticonvulsants are eligible.
• 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.
• Females must not be breastfeeding.
• No clinically significant active infection, as determined by the treating physician

Sponsors & Collaborators

• Indiana University: lead
• Breast Cancer Research Foundation: collaborator
• Geron Corporation: collaborator

Study Sites (1)

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; imetelstat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kathy Miller, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 3, 2010
• First Posted: December 23, 2010
• Study Start: January 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: October 1, 2015
• Last Updated: October 27, 2015

Record last verified: 2015-10

Locations

US (1)