Advanced Non Small Cell Lung Cancer (NSCLC) Clinical Trial
Official title:
A Multicenter, Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations Who Have Progressed on Prior EGFR TKI Treatment
| Verified date | July 2019 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The purpose of this study was to determine if AUY922 had superior efficacy when compared to
chemotherapy agents docetaxel or pemetrexed in patients whose tumor had EGFR mutations.
The primary purpose of this study was to compare the efficacy of AUY922, when administered
i.v. on a once-weekly schedule at 70 mg/m2, versus docetaxel or pemetrexed in adult patients
with advanced NSCLC, whose tumors harbored EGFR activating mutations, and had developed
resistance to EGFR TKI.
| Status | Terminated |
| Enrollment | 59 |
| Est. completion date | November 4, 2015 |
| Est. primary completion date | November 4, 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Patients with histologically or cytologically documented, locally advanced (stage IIIB who are not amenable to combined modality treatment) or recurrent or metastatic (Stage IV) non-small cell lung cancer. 2. Patients must have EGFR gene mutation in their tumors. This can be source - documented by one of the following: • Provide a pathology report that indicates the patient's tumor had EGFR activating mutation in the past. Or: • Perform testing (local or central) in an archival tumor or a fresh baseline biopsy tumor tissue to show the presence of EGFR activating mutation. 3. Patients must have documented clinical benefit (CR, PR, or patients with SD for 6 months or greater) on prior EGFR TKI (e.g. erlotinib or gefitinib) followed by documented progression according to RECIST. 4. Patients must have received prior platinum containing treatment. 5. WHO performance status of 0-1 Exclusion Criteria: 1. Patients who have received more than two prior lines of antineoplastic therapy for advanced disease. Chemotherapy administered as neoadjuvant or adjuvant treatment more than six months prior to study enrollment is not considered a prior line of therapy for purposes of this study. 2. Evidence of spinal cord compression or current evidence of CNS metastases. Screening CT/MRI of the brain is mandatory. Note: Patients who have been treated for CNS metastases by radiation or gamma knife surgery, who been stable for at least 2 months and have discontinued high dose corticosteroids will be eligible for protocol participation 3. Prior treatment with an HSP90 inhibitor |
| Country | Name | City | State |
|---|---|---|---|
| France | Novartis Investigative Site | Creteil | |
| France | Novartis Investigative Site | Marseille cedex 20 | Bouches Du Rhone |
| France | Novartis Investigative Site | Villejuif Cedex | |
| Hong Kong | Novartis Investigative Site | Hong Kong | |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Monza | MB |
| Italy | Novartis Investigative Site | Orbassano | TO |
| Italy | Novartis Investigative Site | Parma | PR |
| Japan | Novartis Investigative Site | Koto ku | Tokyo |
| Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
| Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
| Korea, Republic of | Novartis Investigative Site | Seoul | Seocho Gu |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Netherlands | Novartis Investigative Site | Amsterdam | |
| Netherlands | Novartis Investigative Site | Groningen | |
| Norway | Novartis Investigative Site | Bergen | |
| Norway | Novartis Investigative Site | Oslo | |
| Poland | Novartis Investigative Site | Gdansk | |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Madrid | |
| Taiwan | Novartis Investigative Site | Kuei-Shan Chiang | Taoyuan/ Taiwan ROC |
| Taiwan | Novartis Investigative Site | Taichung | |
| Taiwan | Novartis Investigative Site | Taipei | |
| United Kingdom | Novartis Investigative Site | Leicester | |
| United States | Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr. | Los Angeles | California |
| United States | University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 5 | Madison | Wisconsin |
| United States | Maryland Oncology Hematology, P.A. SC | Rockville | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, France, Hong Kong, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Spain, Taiwan, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) | Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 16 months | |
| Secondary | Overall Response Rate (ORR) | ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all the efficacy assessments was stopped at that time. | 16 months | |
| Secondary | Overall Survival (OS) | OS is defined as the time from the date of randomization to date of death due to any cause. If a death has not been observed by the date of analysis cutoff, then OS was to be censored at the last known date patient was alive. | from randomization until death up to death | |
| Secondary | Disease Control Rate (DCR) | Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1 | baseline, until disease progression up to 24 months | |
| Secondary | Time to Response (TRR) | TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1 | baseline, until disease progression up to 24 months | |
| Secondary | Duration of Response (DOR) | The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1 | baseline, until disease progression up to 24 months | |
| Secondary | Rate of Adverse Events (AEs) | To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel. | baseline, until disease progression up to 24 months | |
| Secondary | Change in Laboratory Paramenters | Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity. | baseline, until disease progression up to 24 months | |
| Secondary | Time to Progression (TTP) | TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1 | baseline, until disease progression up to 24 months |