IPI-504 in NSCLC Patients With ALK Translocations

NCT01228435 | Terminated Phase 2 Results DMC

• 1 other identifier: 10-134
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

IPI-504 blocks a protein that is in cancer cells and is also in normal cells. This protein is called Heat Shock Protein-90 (Hsp90). Hsp90 helps protect certain other proteins from being destroyed by cells. These proteins can mutate to give off signals that allow cancer cells to keep growing. By blocking the function of Hsp90, we hope that the cancer cell will block the mutated protein and cause the cancer cells to die. This drug have been used in other research studies and in the laboratory and information from those other research studies suggests that thsi drug may help to treat lung cancer with ALK mutations. In this research study, we are looking to see what effects IPI-504 has in patients with lung cancer who have an ALK mutation.

Conditions

Lung Cancer; Stage IIIb Lung Cancer; Stage IV Lung Cancer

Keywords

NSCLC; IPI-504; ALK translocation; Hsp90 inhibitor

Outcome Measures

Primary Outcomes (1)

• Response Rate

  The response rate was defined as the number of patients achieving a RECIST 1.0 defined response divided by the number of patients treated and was to be calculated separately for each arm. A response by RECIST criteria means that the pre-defined target lesions (sum of the longest diameters) had to decrease by 30% or more and this response needed to be confirmed on a second scan at least 4 weeks later.

  2 years

Secondary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events

  2 years

Study Arms (2)

ALK-inhibitor naive

EXPERIMENTAL

No prior exposure to ALK-inhibitor

Drug: IPI-504

ALK-inhibitor pre-treated

EXPERIMENTAL

Prior exposure to ALK inhibitor

Drug: IPI-504

Interventions

IPI-504 DRUG

Given intravenously twice weekly for 2 weeks followed by 10 day off treatment

ALK-inhibitor naive; ALK-inhibitor pre-treated

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically confirmed diagnosis of Stage IIIb (with malignant pleural or pericardial effusion), Stage IV, or recurrent NSCLC.
• Patients must have demonstrated ALK mutation
• There is no requirement for a minimum or maximum number of prior therapies, however, patients must have refused, be intolerant to or already received at least on standard systemic therapy for lung cancer
• Measureable disease by RECIST criteria. If a patient has received radiation therapy then measurable disease must be outside the radiation field.
• years of age or older
• Life expectancy of at least 3 months
• ECOG performance status of 0-2
• Baseline studies for determining eligibility, except for ALK mutation status, must be completed within 30 days of first study dose.
• CT scan must be completed within 28 days prior to first study dose
• Women of child-bearing potential (WBCP) defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months must have a negative serum or urine pregnancy test within 2 weeks of first study dose
• All WCBP and all sexually active male patients must agree to use adequate methods of birth control throughout the study

You may not qualify if:

• Treatment for NSCLC with any approved or investigational product within 2 weeks of Cycle 1, Dose 1 for any small molecule therapy; within 4 weeks of Cycle 1, Dose 1 for any biologic or any conventional chemotherapy.
• Concurrent radiation therapy is not permitted
• Use of a medication or food that is clinically relevant CYP3A inhibitor or inducer within 2 weeks prior to Cycle 1, Dose 1
• Laboratory values as outlined in the protocol
• Baseline QT corrected using Fridericia's correction method (QTcf) \> 470ms. Patients with left bundle branch block are eligible regardless of QTcf, as long as serum troponin is normal or undetectable
• Presence of active infection or systemic use of antibiotics within 72 hours of treatment
• Significant co-morbid condition or disease which in the judgment of the investigator would place the patient at undue risk or interfere with the study
• Women who are pregnant or lactating
• Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor
• Sinus bradycardia secondary to intrinsic conduction system disease. Patients with sinus bradycardia secondary to pharmacologic treatment may enroll if withdrawal of the treatment results in normalization of the resting heart rate to within normal limits
• Active keratitis or keratoconjunctivitis
• Alkaline phosphatase \> 1.5 x ULN. Patients with bone metastases and an alkaline phosphatase level \> 1/5 x ULN and less than or equal to 3 x ULN are eligible if they meet the criteria outlined in the protocol
• Prothrombin time (PT) and partial thromboplastin time (PTT) \> 1.5 x ULN unless the patient is receiving warfarin. If the patient is receiving warfarin, the international normalized ratio must be within therapeutic range
• Patients with clinically active brain metastasis or an uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous meningitis. Patients with clinically stable brain metastasis are eligible.
• Patients with prior hepatic resection or hepatic-directed therapy

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Infinity Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

tanespimycin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was unable to accrue sufficient participants due to competing studies. Therefore, the study results are not sufficiently powered to draw any conclusions.

Results Point of Contact

• Title: Lecia Sequist
• Organization: Massachusetts General Hospital

lvsequist@partners.org

617-726-7812

Study Officials

• Lecia V. Sequist, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 25, 2010
• First Posted: October 26, 2010
• Study Start: October 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: December 4, 2017
• Results First Posted: October 23, 2013

Record last verified: 2017-10

Locations

US (2)