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Trial record 1 of 1 for:    NCT#01772004
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Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)

This study is currently recruiting participants.
Verified September 2017 by EMD Serono
Sponsor:
ClinicalTrials.gov Identifier:
NCT01772004
First Posted: January 21, 2013
Last Update Posted: September 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono
  Purpose

This is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in subjects with selected tumor indications. New recruitment is open for all active cohorts.

Active cohorts: Escalation revised dosing regimen cohort.

Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .


Condition Intervention Phase
Solid Tumors Drug: Avelumab Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Dose Limiting Toxicity [ Time Frame: Up to 3 weeks ]
  • Confirmed Best Overall Response (BOR) as per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) for Efficacy Expansion Cohorts [ Time Frame: Every 6 weeks for first 12 months, then 12-weekly until end of treatment and post treatment every 3 months ( up to 52 months) ]

Secondary Outcome Measures:
  • Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 [ Time Frame: Screening up to 10 weeks after last treatment ]
  • Pharmacokinetic parameters: AUC (0-t), AUC (0-infinity), λz, Cmax, Tmax, T(1/2) of avelumab [ Time Frame: Every 6-week up to Week 25 ]
  • Immune-related Best Overall Response (irBOR) and Best Overall Response (BOR) according to modified Immune-related response criteria (irRC) and RECIST version 1.1, respectively [ Time Frame: Time from inclusion in the trial until the date of first documented progression or discontinuation from the study due to any cause, up to 1 year after last treatment ]
  • Immune-related Progression-Free Survival (irPFS) time and Progression-Free Survival (PFS) Time according to modified irRC and RECIST version 1.1 , respectively [ Time Frame: Time from inclusion in the trial until first observation of progressive disease or death when death occurs within 12 weeks of the last tumor assessment or first administration of trial treatment (whichever is later) up to 1 year after last treatment ]
  • Overall Survival Time [ Time Frame: Time from randomization to death anticipated up to 2 years after last treatment ]
  • Pharmacodynamic profile of avelumab to include serum levels of cytokines [ Time Frame: Up to Week 25 ]
  • Number of subjects with anti-avelumab antibodies [ Time Frame: Every 6-week up to Week 25 ]
  • Level of PD-L1 tumor expression [ Time Frame: Every 6-week up to Week 25 ]
  • Unconfirmed response according to RECIST 1.1 per investigator assessment for Primary expansion cohort [ Time Frame: Week 13 ]
  • Duration of response according to modified irRC and RECIST 1.1 per investigator assessment [ Time Frame: Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment ]
  • Progression Free Survival time according to RECIST 1.1 for Efficacy Expansion Cohorts [ Time Frame: Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment ]
  • Duration of response according to RECIST 1.1 for Efficacy Expansion cohorts [ Time Frame: Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment ]
  • Confirmed BOR as per RECIST 1.1 as adjudicated by an Independent Endpoint Review Committee (IERC) for secondary urothelial carcinoma cohort [ Time Frame: Time Frame: Every 6 weeks for first 12 months, then 12-weekly until end of treatment and post treatment every 3 months ( up to 52 months) ]

Estimated Enrollment: 1756
Actual Study Start Date: January 31, 2013
Estimated Study Completion Date: May 1, 2018
Estimated Primary Completion Date: May 1, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Avelumab Drug: Avelumab
Avelumab will be administered in study location using a protocol-defined dose escalation scheme until confirmed progression, unacceptable toxicity, or if any criterion for withdrawal from the trial or investigational medicinal product occurs. After determination of the dose and regimen for Expansion Phase, avelumab will be administered to subjects divided into 4 primary cohorts: Non-small cell lung cancer (NSCLC) post platinum doublet, NSCLC first-line, gastric/gastroesophageal junction (GEJ) cancer and metastatic breast cancer (MBC); 8 secondary cohorts: Colorectal cancer (CRC), castrate-resistant prostate cancer (CRPC), melanoma, ovarian cancer, adrenocortical carcinoma (ACC) mesothelioma, urothelial carcinoma, and renal cell carcinoma (RCC); and 4 efficacy expansion cohorts: gastric and GEJ cancer (third line), ovarian cancer (second-line only), urothelial carcinoma, and head and neck squamous cell carcinoma (HNSCC).
Other Names:
  • MSB0010718C
  • Anti PD-L1

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for dose escalation and expansion phase:

  • Signed written informed consent
  • Male or female subjects aged greater than or equal to 18 years
  • Subjects must have histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for subjects in dose escalation
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
  • Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST 1.1, except for subjects with metastatic castrate-resistant prostate cancer (mCRPC) or metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease without a measureable lesion
  • Adequate hematological, hepatic and renal function as defined in the protocol
  • Effective contraception for both male and female subjects if the risk of conception exists
  • Other protocol defined inclusion criteria could apply

Inclusion Criteria for expansion phase:

  • Subjects must have relapsed, refractory, or progressive disease following last line of treatment (with the exception of the gastric and gastroesophageal junction (GEJ) cancer cohort, which does not require progression). Availability of tumor archival material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in the expansion cohorts. For subjects in the MBC cohort, the biopsy or surgical specimen must have been collected within 90 days prior to the first investigational medicinal product (IMP) administration. Specifically, the following will be required:
  • NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or stage IV NSCLC that has progressed after 1 line of platinum-containing doublet chemotherapy. Subjects should have received only 1 line of platinum-containing treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing regimen is not sufficient for eligibility because not received in the context of a metastatic disease). Subjects in the NSCLC cohort will only be enrolled in USA
  • NSCLC first line: Stage IV (per 7th International Association for the Study of Lung Cancer [IASLC] classification) or recurrent NSCLC that is histologically proven. Subjects must not have received treatment for their metastatic or recurrent disease. No activating epidermal growth factor receptor (EGFR) mutation nor ALK translocation/re-arrangement
  • Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with first-line chemotherapy combination with or without disease progression. Subjects should have received no more than 1 line of treatment for metastatic disease. Subjects should not have been treated with trastuzumab (but can be Human Epidermal growth factor Receptor 2 [HER2] positive). Subjects who received any platinum containing doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately candidates for surgery will also be eligible, as long as they did not have progressive disease after completion of the neoadjuvant chemotherapy. In addition, subjects with gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte count is as defined in the protocol
  • MBC: Subjects must have histologically confirmed locally advanced or MBC and have tumor that is refractory to or progressive after standard of care therapy. Subjects must have received no more than 3 prior lines of cytotoxic therapy for metastatic disease. Subjects must have received a taxane and an anthracycline, unless contra-indicated
  • Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC, mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol
  • Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer (platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as defined in the protocol

    • Other protocol defined inclusion criteria for expansion phase could apply

Exclusion Criteria for dose escalation and expansion phase:

  • Concurrent treatment with a non-permitted drug
  • Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
  • Concurrent anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of trial treatment; or concurrent systemic therapy with immunosuppressive agents, use of hormonal agents within 7 days before the start of trial treatment as defined in the protocol. Note: Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.
  • Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
  • Rapidly progressive disease (for example, tumor lysis syndrome)
  • Active or history of central nervous system metastases
  • Receipt of any organ transplantation including allogeneic stem-cell transplantation
  • Significant acute or chronic infections as defined in the protocol
  • Active or history of any autoimmune disease (subjects with diabetes Type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies
  • Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
  • Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0, however sensory neuropathy less than or equal to Grade 2 is acceptable
  • Pregnancy or lactation period
  • Known alcohol or drug abuse
  • Clinically significant (that is, active) cardiovascular disease
  • All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the investigator, might impair the subject's tolerance of trial treatment
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Legal incapacity or limited legal capacity
  • Non-oncology vaccine therapies for prevention of infection disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration. Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine
  Contacts and Locations
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): NCT01772004


Contacts
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center +49 6151 72 5200 service@merckgroup.com

Locations
United States, Massachusetts
For Recruiting Locations in the United States, please Contact U.S. Medical Information Recruiting
Rockland, Massachusetts, United States
Contact    888-275-7376      
Belgium
Please contact the Merck KGaA Communication Center Active, not recruiting
Leuven, Belgium
Czechia
Please contact the Merck KGaA Communication Center Active, not recruiting
Praha, Czechia
France
Please contact the Merck KGaA Communication Center Active, not recruiting
Paris, France
Germany
Please contact the Merck KGaA Communication Center Active, not recruiting
Berlin, Germany
Hungary
Please contact the Merck KGaA Communication Center Active, not recruiting
Budapest, Hungary
Korea, Republic of
Please contact the Merck KGaA Communication Center Active, not recruiting
Seoul, Korea, Republic of
Poland
Please contact the Merck KGaA Communication Center Active, not recruiting
Warszawa, Poland
Taiwan
Please contact the Merck KGaA Communication Center Active, not recruiting
Taipei, Taiwan
United Kingdom
Please contact the Merck KGaA Communication Center Active, not recruiting
London, United Kingdom
Sponsors and Collaborators
EMD Serono
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
  More Information

Publications:
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01772004     History of Changes
Other Study ID Numbers: EMR 100070-001
2013-002834-19 ( EudraCT Number )
First Submitted: January 14, 2013
First Posted: January 21, 2013
Last Update Posted: September 14, 2017
Last Verified: September 2017

Keywords provided by EMD Serono:
Solid Tumors
MSB0010718C
Phase 1
Pharmacokinetic
anti PD-L1
Non-small cell lung cancer (NSCLC)
Metastatic breast cancer (MBC)
Gastric and gastroesophageal junction (GEJ) cancer
Ovarian cancer
Colorectal cancer (CRC)
Castrate-resistant prostate cancer (CRPC)
Melanoma
Urothelial carcinoma
Bladder cancer
Head and neck squamous cell carcinoma (HNSCC)
Renal cell carcinoma (RCC)
Adrenocortical carcinoma (ACC)

Additional relevant MeSH terms:
Neoplasms