Clinical trial NCT02659020: A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
Official title: A Phase 1b (Open-Label)/Phase 2 (Randomized, Double-Blinded) Study Evaluating Gemcitabine and Docetaxel With or Without Olaratumab in the Treatment of Advanced Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Soft Tissue Sarcoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-01-20
Enrollment: 310
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety and efficacy of two anti-cancer drugs (gemcitabine and docetaxel) with and without the study drug known as olaratumab in participants with advanced soft tissue sarcoma (STS) or STS that has spread to another part(s) of the body.


Eligibility criteria: Inclusion Criteria:

* The participant may have no more than 2 prior lines of systemic therapies (neoadjuvant and adjuvant therapies will not be considered as a prior line of therapy) for advanced or metastatic disease and is suitable to receive gemcitabine and docetaxel therapy. All previous therapies must have completed ≥ 3 weeks (21 days) prior to first dose of study drug.
* In the Phase 2 part, prior olaratumab/doxorubicin combination therapy in 1 prior treatment line is allowed.

  * Prior olaratumab therapy must have been received with doxorubicin as indicated on the olaratumab label.
  * Prior olaratumab therapy must have included at least 2 full cycles of olaratumab/doxorubicin (that is, a minimum of 4 doses of olaratumab).
  * Participants, who completed at least 2 cycles of combination olaratumab/doxorubicin therapy then discontinued doxorubicin due to toxicity or maximum dosing and proceeded to olaratumab monotherapy, are eligible.
  * The most recent dose of olaratumab must have been received within 180 days of randomization in this study.
* Availability of tumor tissue is mandatory for study eligibility. The participant must have consented to provide archived formalin-fixed paraffin-embedded tumor tissue or be subject to a pre-treatment re-biopsy of primary or metastatic tumor tissue for future central pathology review and translational research (if archived tissue is unavailable).
* The participant has adequate hematologic, organ, and coagulation function within 2 weeks (14 days) prior to enrollment (Phase 1b) or randomization (Phase 2).

Exclusion Criteria:

* The participant is diagnosed with gastrointestinal stromal tumor (GIST) or Kaposi sarcoma.
* The participant has active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment (Phase 1b) or randomization (Phase 2). Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days, and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment (Phase 1b) /randomization (Phase 2) to rule out brain metastasis.
* The participant has received prior treatment with gemcitabine or docetaxel. Note: Participants previously enrolled in the I5B-MC-JGDJ (NCT02451943) or any other blinded study with olaratumab are not eligible to participate in this trial.
* The participant has electively planned or will require major surgery during the course of the study.
* Females who are pregnant or breastfeeding.
* The participant has an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).

Primary outcomes:
measure: Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: Cycle 1 (Up To 21 Days)
measure: Phase 2: Overall Survival (OS) (Olaratumab-Naive)
timeFrame: Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Secondary outcomes:
measure: Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
timeFrame: Pre-dose, 5 minutes (min), 1, 4, 4.5, 24, 96, 168, 336 hours (h) post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
measure: Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab
timeFrame: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1
measure: Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab
timeFrame: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
measure: Phase 1b/2: PK: Cmax of Gemcitabine
timeFrame: Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
measure: Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine
timeFrame: Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
measure: Phase 1b/2: PK: Cmax of Docetaxel
timeFrame: 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
measure: Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel
timeFrame: 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
measure: Phase 1b/2: Population PK: Clearance of Olaratumab
timeFrame: Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
measure: Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab
timeFrame: Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
measure: Phase 2: Overall Survival (Olaratumab Pre-Treated)
timeFrame: Baseline to Date of Death Due to Any Cause (Up To 38 Months)
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)
measure: Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
timeFrame: Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)
measure: Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)
timeFrame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)
measure: Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
timeFrame: Baseline to Follow-up (Up To 24 Months)
measure: Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.
timeFrame: Baseline to Follow-up (Up to 33 months)
measure: Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)
timeFrame: Cycle 1 (Day 1), Follow-up (Up to 38 Months)
measure: Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
timeFrame: Baseline through Follow-Up (Up to 38 Months)
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists PC
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Cancer Center
state: Nebraska
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists & Research Institute, LLC
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lille Cedex
country: France
facility: Centre Oscar Lambret
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: München
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
state: Bayern
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow
state: Brandenburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
state: Ramat Gan
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Petah Tiqva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Candiolo
country: Italy
facility: Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro
state: Torino
city: Torino
country: Italy
facility: Humanitas Gradenigo
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im Marii Sklodowskiej-Curie
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: London
country: United Kingdom
facility: University College Hospital - London
state: Greater London
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
state: Greater London
city: Bebbington
country: United Kingdom
facility: Clatterbridge Cancer Centre
state: Merseyside
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: