A Study of Olaratumab (IMC-3G3) in Prostate Cancer

NCT01204710 | Completed Phase 2 Results DMC

• 4 other identifiers: 13938I5B-IE-JGDDCP15-08052009-018015-11
• Study Type: interventional
• Target: 123
• Locations: 7 countries
• Sites: 40

Brief Summary

This is a study evaluating the safety and efficacy of the monoclonal antibody olaratumab plus mitoxantrone plus prednisone compared to mitoxantrone plus prednisone in metastatic castration-refractory prostate cancer following disease progression or intolerance on docetaxel-based chemotherapy.

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is measured from randomization to the earliest date of the following events: PD according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version (v) 1.1, is a ≥20% increase in the sum of diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 millimeter (mm), the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions, unequivocal evidence of progression by bone scan, clinical progression or death from any cause. For participants who had no documented PD or death or had started new anti-cancer therapy or were lost to follow-up, PFS was censored at their last tumor assessment.

  Randomization to Measured PD or Death Due to Any Cause Up to 23 Months

Secondary Outcomes (10)

• Overall Survival (OS)

  Randomization to Death Due to Any Cause Up to 36 Months

• Percentage of Participants Who Achieved a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

  Randomization to Objective PD or Death Up to 23 Months

• Percentage of Participants With a ≥50% Decrease in Prostate Specific Androgen (PSA) From Pretreatment to Any Time

  Pretreatment to PD Up to 23 Months

• Percentage of Participants With a ≥30% Decrease in PSA From Pretreatment to Week 12

  Pretreatment through Week 12

• Summary Listing of Participants Reporting Treatment-Emergent Adverse Events (TEAE)

  From Start of Treatment Through Study Completion Up to 36 months

Other Outcomes (1)

• Number of Participants Who Died During Study

  From Start of Treatment through Study Completion up to 36 Months

Study Arms (2)

Olaratumab + Mitoxantrone

EXPERIMENTAL

1 cycle = 3 weeks (21 days)

Biological: Olaratumab; Drug: Mitoxantrone; Drug: Prednisone

Mitoxantrone: Optional Olaratumab Monotherapy

ACTIVE COMPARATOR

1 cycle = 3 weeks (21 days) Participants who experience progressive disease (PD) have the option to receive olaratumab monotherapy treatment.

Drug: Mitoxantrone; Drug: Prednisone

Interventions

Olaratumab BIOLOGICAL

15 milligrams per kilogram (mg/kg) intravenous (IV) Days 1 and 8

Also known as: IMC-3G3, LY3012207

Olaratumab + Mitoxantrone

Mitoxantrone DRUG

Mitoxantrone 12 milligrams per square meter (mg/m²) IV Day 1 Mitoxantrone is to be administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²)

Mitoxantrone: Optional Olaratumab Monotherapy; Olaratumab + Mitoxantrone

Prednisone DRUG

5 mg orally (PO) twice daily (BID) on each day

Mitoxantrone: Optional Olaratumab Monotherapy; Olaratumab + Mitoxantrone

Eligibility Criteria

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

You may qualify if:

• histologically-confirmed adenocarcinoma of the prostate
• radiographic evidence of metastatic prostate cancer (Stage M1 or D2)
• has prostate cancer unresponsive or refractory to medical or surgical castration with a serum testosterone level of \<50 nanograms per milliliter (ng/mL)
• has had disease progression or intolerance on docetaxel-based therapy
• prostate-specific antigen (PSA) ≥10 ng/mL
• all clinically significant toxic effects of prior surgery, radiotherapy, chemotherapy or hormonal therapy have resolved to ≤Grade 1, based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.02
• participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• adequate hematologic function
• adequate hepatic function
• adequate renal function
• urinary protein is ≤1 on dipstick or routine analysis
• life expectancy of more than 3 months
• fertile man with partners that are women of childbearing potential must use an adequate method of contraception during the study
• signed Informed Consent Document

You may not qualify if:

• concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive or in situ neoplasms
• The participant has received more than 1 prior cytotoxic chemotherapy regimen for metastatic disease
• prior therapy with mitoxantrone for advanced prostate cancer
• The participant has a history of symptomatic congestive heart failure or has a pre study echocardiogram or multigated acquisition scan with left ventricular ejection fraction that is ≥10% below the lower limit of normal institutional range
• history of prior treatment with other agents that directly inhibit platelet-derived growth factor (PDGF) or platelet-derived growth factor receptors (PDGFR)
• known allergy to any of the treatment components: olaratumab, mitoxantrone, and/or prednisone
• radiotherapy within 21 days prior to first dose of olaratumab
• any investigational therapy within 30 days of randomization
• is receiving corticosteroids at a dose \>5 mg prednisone PO BID or equivalent
• received prior strontium-89, rhenium-186, rhenium-188, or samarium-153 radionucleotide therapy and has either ongoing evidence of bone marrow dysfunction or poorly controlled bone pain
• has any ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, psychiatric illness, active bleeding or pathological condition that carries a high risk of bleeding, or any other serious uncontrolled medical disorders
• known or suspected brain or leptomeningeal metastases
• known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (40)

ImClone Investigational Site

Charleroi, 6000, Belgium

Location

ImClone Investigational Site

Edegem, 2650, Belgium

Location

ImClone Investigational Site

Liège, 4000, Belgium

Location

ImClone Investigational Site

Olomouc, 77520, Czechia

Location

ImClone Investigational Site

Prague, 12808, Czechia

Location

ImClone Investigational Site

Prague, 15006, Czechia

Location

ImClone Investigational Site

Aachen, 57074, Germany

Location

ImClone Investigational Site

Augsburg, 86150, Germany

Location

ImClone Investigational Site

Bonn, 53177, Germany

Location

ImClone Investigational Site

Dresden, 01307, Germany

Location

ImClone Investigational Site

Essen, 45122, Germany

Location

ImClone Investigational Site

Frankfurt, 60590, Germany

Location

ImClone Investigational Site

Freiburg im Breisgau, 79106, Germany

Location

ImClone Investigational Site

Mainz, 55131, Germany

Location

ImClone Investigational Site

Mannheim, 68167, Germany

Location

ImClone Investigational Site

Münster, 48149, Germany

Location

ImClone Investigational Site

Rostock, 18055, Germany

Location

ImClone Investigational Site

Budapest, 1106, Hungary

Location

ImClone Investigational Site

Debrecen, 4032, Hungary

Location

ImClone Investigational Site

Kecskemét, 6000, Hungary

Location

ImClone Investigational Site

Miskolc, 3526, Hungary

Location

ImClone Investigational Site

Nyíregyháza, 4400, Hungary

Location

ImClone Investigational Site

Pécs, 7624, Hungary

Location

ImClone Investigational Site

Szeged, 6725, Hungary

Location

ImClone Investigational Site

Meldola, 47014, Italy

Location

ImClone Investigational Site

Milan, 20123, Italy

Location

ImClone Investigational Site

Roma, 161, Italy

Location

ImClone Investigational Site

Rozzano, 20089, Italy

Location

ImClone Investigational Site

Trento, 38100, Italy

Location

ImClone Investigational Site

Krakow, 31-115, Poland

Location

ImClone Investigational Site

Lublin, 20-090, Poland

Location

ImClone Investigational Site

Poznan, 61-485, Poland

Location

ImClone Investigational Site

Warsaw, 02-781, Poland

Location

ImClone Investigational Site

Barcelona, 8003, Spain

Location

ImClone Investigational Site

Barcelona, 8036, Spain

Location

ImClone Investigational Site

Madrid, 28041, Spain

Location

ImClone Investigational Site

Palma de Mallorca, 7014, Spain

Location

ImClone Investigational Site

Pamplona - Navarra, 31008, Spain

Location

ImClone Investigational Site

Sabadell - Barcelona, 8208, Spain

Location

ImClone Investigational Site

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaratumab; Mitoxantrone; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Limitations and Caveats

Efficacy analysis for the follow-on treatment is exploratory, therefore, efficacy analysis for follow-on treatment are not included in this clinical trial results.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 17, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: October 1, 2013
• Last Updated: September 20, 2019
• Results First Posted: November 2, 2018

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

ES (7); DE (11); BE (3); HU (7); PL (4); IT (5); CZ (3)