NCT00642941

A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

Terminated Phase 2 Results posted Last updated 3 February 2021

What this trial tests

Phase 2 trial testing RG1507 in Sarcoma in 317 participants. Terminated before completion.

Timeline

18 December 2007

Primary endpoint
19 February 2014

19 February 2014

Quick facts

Lead sponsor	Hoffmann-La Roche
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	317
Start date	18 December 2007
Primary completion	19 February 2014
Estimated completion	19 February 2014
Sites	41 locations across France, Italy, Netherlands, Sweden, United Kingdom, Germany, Norway, Canada

Drugs / interventions tested

• RG1507 — full drug profile →

Conditions studied

• Sarcoma — all drugs for Sarcoma →

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

2 and older, any sex, with Sarcoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 Primary · Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression)

Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

Group	Value	95% CI
Cohort 2: Ewings Sarcoma Secondary Cohort	11.11
Cohort 4: Osteosarcoma	2.5
Cohort 5: Synovial Sarcoma	4.0
Cohort 6: Rhabdomyosarcoma	4.88
Cohort 7a: Alveolar Soft Part Sarcoma	0
Cohort 7b: Desmoplastic Small Round Cell Tumors.	0
Cohort 7c: Extraskeletal Myxoid Chondrosarcoma	0
Cohort 7d: Clear Cell Sarcoma	0
Cohort 7e: Myxoid Liposarcoma	0
Cohort 8: Diagnosis Not Specified	0

Progression-Free Survival (PFS) Rate According to WHO Response Criteria at 18 Weeks From Start of R2607 Treatment in Cohort 1 Primary · Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression)

The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response) at 18 weeks from start of treatment.

Group	Value	95% CI
Cohort 1: Ewings Sarcoma Primary Cohort	15.81

Percentage of Participants With Adverse Events (AEs) in Cohort 1 and 2 Primary · Baseline up to 6 years

Group	Value	95% CI
Cohort 1: Ewings Sarcoma Primary Cohort	96
Cohort 2: Ewings Sarcoma Secondary Cohort	96

Percentage of Participants With Complete or Partial Response According to WHO Response Criteria in Cohort 1 Secondary · Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

Group	Value	95% CI
Cohort 1: Ewings Sarcoma Primary Cohort	8.57

PFS Rate According to WHO Response Criteria at 18 Weeks From Start of R1507 Treatment in Cohorts 2 to 8 Secondary · Baseline, every 6 weeks until disease progression (up to 18 weeks)

The PFS survival rate is a landmark analysis of progression-free survival at 18 weeks from start of treatment. Progression-free survival rate at 18 weeks is a dichotomous endpoint, with a patient categorized as alive (with either stable disease or objective response at 18 weeks) from start of treatment.

Group	Value	95% CI
Cohort 2: Ewings Sarcoma Secondary Cohort	17.16
Cohort 4: Osteosarcoma	19.69
Cohort 5: Synovial Sarcoma	4.00
Cohort 6: Rhabdomyosarcoma	7.32
Cohort 7a: Alveolar Soft Part Sarcoma	45.40
Cohort 7b: Desmoplastic Small Round Cell Tumors.	8.16
Cohort 7c: Extraskeletal Myxoid Chondrosarcoma	62.34
Cohort 7e: Myxoid Liposarcoma	0
Cohort 7d: Clear Cell Sarcoma	8.33
Cohort 8: Diagnosis Not Specified	22.86

Percentage of Participants With AEs in Cohorts 3-8 Secondary · Baseline up to 6 years

Group	Value	95% CI
Cohort 3: Ewings Sarcoma Expanded Cohort	85.7
Cohort 4: Osteosarcoma	100
Cohort 5: Synovial Sarcoma	100
Cohort 6: Rhabdomyosarcoma	95
Cohort 7a: Alveolar Soft Part Sarcoma	91
Cohort 7b: Desmoplastic Small Round Cell Tumors.	86
Cohort 7c: Extraskeletal Myxoid Chondrosarcoma	100
Cohort 7d: Clear Cell Sarcoma	100
Cohort 7e: Myxoid Liposarcoma	100
Cohort 8: Diagnosis Not Specified	100

Duration of Response (DOR) According to WHO Response Criteria in Cohorts 1 to 8 Secondary · Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Complete response is the disappearance of all known disease, determined by two consecutive observations not less than 4 weeks apart. Partial response is \>=50% decrease in the total tumor load of the lesions that have been measured to determine the effect of therapy not less than four weeks apart. The observations must be consecutive.

Group	Value	95% CI
Cohort 1: Ewings Sarcoma Primary Cohort	44.29	18 – NA
Cohort 2: Ewings Sarcoma Secondary Cohort	42.86	18.14 – NA
Cohort 4: Osteosarcoma	NA	30.14 – NA
Cohort 5: Synovial Sarcoma	13.14	13.14 – NA
Cohort 6: Rhabdomyosarcoma	NA	21 – NA

Time to Progression (TTP) According to WHO Response Criteria in Cohorts 1 to 8 Secondary · Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

TTP is defined as the time from date of randomization until objective tumor progression. According to the WHO Response Criteria, objective tumor progression is \> 25% increase in the area of one or more measurable lesions or the appearance of new lesions.

Group	Value	95% CI
Cohort 1: Ewings Sarcoma Primary Cohort	6.00	5.29 – 9.71
Cohort 2: Ewings Sarcoma Secondary Cohort	6.00	5.71 – 8.14
Cohort 4: Osteosarcoma	5.71	5.57 – 7.00
Cohort 5: Synovial Sarcoma	6.00	5.57 – 6.43
Cohort 6: Rhabdomyosarcoma	5.50	5.14 – 6.14
Cohort 7a: Alveolar Soft Part Sarcoma	11.14	6.00 – 17.71
Cohort 7b: Desmoplastic Small Round Cell Tumors.	6.14	5.86 – 11.14
Cohort 7c: Extraskeletal Myxoid Chondrosarcoma	18.00	5.71 – NA
Cohort 7d: Clear Cell Sarcoma	5.57	5.14 – 5.86
Cohort 7e: Myxoid Liposarcoma	5.86	5.29 – 8.43
Cohort 8: Diagnosis Not Specified	6.14	5.86 – 10.00

Overall Survival (OS) in Cohorts 1 to 8 Secondary · Baseline until death (up to 6 years)

OS was measured from the time of study registration to the date of death or was censored at the date of last contact.

Group	Value	95% CI
Cohort 1: Ewings Sarcoma Primary Cohort	29.57	20.57 – 37.57
Cohort 2: Ewings Sarcoma Secondary Cohort	43.57	33.29 – 69.00
Cohort 4: Osteosarcoma	37.14	25.57 – NA
Cohort 5: Synovial Sarcoma	40.71	21.71 – 64.14
Cohort 6: Rhabdomyosarcoma	30.86	21.57 – 50.00
Cohort 7a: Alveolar Soft Part Sarcoma	42.43	42.43 – NA
Cohort 7b: Desmoplastic Small Round Cell Tumors.	40.86	23.57 – NA
Cohort 7c: Extraskeletal Myxoid Chondrosarcoma	NA	NA – NA
Cohort 7d: Clear Cell Sarcoma	17.00	9.14 – NA
Cohort 7e: Myxoid Liposarcoma	36.00	33.14 – NA
Cohort 8: Diagnosis Not Specified	17.43	13.00 – 30.14

PFS According to WHO Response Criteria in Cohorts 1 to 8 Secondary · Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years)

PFS is defined as the duration of time from start of treatment to time of objective progression or death.

Group	Value	95% CI
Cohort 1: Ewings Sarcoma Primary Cohort	6.00	5.29 – 9.57
Cohort 2: Ewings Sarcoma Secondary Cohort	6.00	5.71 – 8.14
Cohort 4: Osteosarcoma	5.71	5.57 – 6.43
Cohort 5: Synovial Sarcoma	6.00	5.43 – 6.14
Cohort 6: Rhabdomyosarcoma	5.43	5.14 – 6.14
Cohort 7a: Alveolar Soft Part Sarcoma	11.14	5.71 – 11.71
Cohort 7b: Desmoplastic Small Round Cell Tumors.	6.14	5.86 – 11.14
Cohort 7c: Extraskeletal Myxoid Chondrosarcoma	18.00	5.71 – NA
Cohort 7d: Clear Cell Sarcoma	5.57	5.14 – 5.86
Cohort 7e: Myxoid Liposarcoma	5.86	5.29 – 8.43
Cohort 8: Diagnosis Not Specified	6.14	5.86 – 10

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 6 years. Reporting threshold: 0.05%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Ewings Sarcoma Primary Cohort

Serious: 11/70 (16%)

Deaths: 9/70

Cohort 2: Ewings Sarcoma Secondary Cohort

Serious: 13/54 (24%)

Deaths: 5/54

Cohort 3: Ewings Sarcoma Expanded Cohort

Serious: 1/7 (14%)

Deaths: 2/7

Cohort 4: Osteosarcoma

Serious: 4/40 (10%)

Deaths: 7/40

Cohort 5: Synovial Sarcoma

Serious: 5/25 (20%)

Deaths: 3/25

Cohort 6: Rhabdomyosarcoma

Serious: 4/41 (10%)

Deaths: 3/41

Cohort 7a: Alveolar Soft Part Sarcoma

Serious: 1/23 (4%)

Deaths: 1/23

Cohort 7b: Desmoplastic Small Round Cell Tumors

Serious: 1/14 (7%)

Deaths: 0/14

Cohort 7c: Extraskeletal Myxoid Chondrosarcoma

Serious: 0/11 (0%)

Deaths: 0/11

Cohort 7d: Clear Cell Sarcoma

Serious: 3/9 (33%)

Deaths: 1/9

Cohort 7e: Myxoid Liposarcoma

Serious: 2/12 (17%)

Deaths: 1/12

Cohort 8: Diagnosis Not Specified

Serious: 4/11 (36%)

Deaths: 2/11

Serious adverse events (47 terms)

Reaction	System	Cohort 1: Ewings Sarcoma P…	Cohort 2: Ewings Sarcoma S…	Cohort 3: Ewings Sarcoma E…	Cohort 4: Osteosarcoma	Cohort 5: Synovial Sarcoma	Cohort 6: Rhabdomyosarcoma	Cohort 7a: Alveolar Soft P…	Cohort 7b: Desmoplastic Sm…	Cohort 7c: Extraskeletal M…	Cohort 7d: Clear Cell Sarc…	Cohort 7e: Myxoid Liposarc…	Cohort 8: Diagnosis Not Sp…
Somnolence	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—
Haemorrhage	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—
Orthostatic hypotension	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—
Thrombosis	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Inflammation	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Mental status changes	Psychiatric disorders	—	—	—	—	—	—	—	—	—	—	—	—
Spinal compression fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Facial palsy	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Intestinal perforation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (193 terms — click to expand)

Reaction	System	Cohort 1: Ewings Sarcoma P…	Cohort 2: Ewings Sarcoma S…	Cohort 3: Ewings Sarcoma E…	Cohort 4: Osteosarcoma	Cohort 5: Synovial Sarcoma	Cohort 6: Rhabdomyosarcoma	Cohort 7a: Alveolar Soft P…	Cohort 7b: Desmoplastic Sm…	Cohort 7c: Extraskeletal M…	Cohort 7d: Clear Cell Sarc…	Cohort 7e: Myxoid Liposarc…	Cohort 8: Diagnosis Not Sp…
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Blood lactate dehydrogenase increased	Investigations	—	—	—	—	—	—	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Infusion related reaction	General disorders	—	—	—	—	—	—	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Haemoglobinaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Somnolence, Pneumonia, Deep vein thrombosis, Haemorrhage, Orthostatic hypotension, Thrombosis, Tumour haemorrhage, Fatigue.

Data from ClinicalTrials.gov NCT00642941 adverse events section.

Sponsor's own description

The study was primarily designed to determine objective response, progression-free survival (PFS), and the safety and tolerability of R1507 in participants with recurrent or refractory Ewing's sarcoma, osteosarcoma, synovial sarcoma, rhabdomyosarcoma and other sarcomas including alveolar soft part sarcoma, desmoplastic small round cell tumor, extraskeletal myxoid chondrosarcoma, clear cell sarcoma, and myxoid liposarcoma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. R1507, a monoclonal antibody to the insulin-like growth factor 1 receptor, in patients with recurrent or refractory Ewing sarcoma family of tumors: results of a phase II Sarcoma Alliance for Research through Collaboration study.
   Pappo AS, Patel SR, Crowley J, Reinke DK, et al · · 2011 · cited 261× · PMID 22025149 · DOI 10.1200/jco.2010.34.0000
2. Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies.
   Abarrategi A, Tornin J, Martinez-Cruzado L, Hamilton A, et al · · 2016 · cited 155× · PMID 27366153 · DOI 10.1155/2016/3631764
3. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature.
   PosthumaDeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. · · 2011 · cited 153× · PMID 21461590 · DOI 10.1007/s10585-011-9384-x
4. Current and Future Treatment Strategies for Rhabdomyosarcoma.
   Chen C, Dorado Garcia H, Scheer M, Henssen AG. · · 2019 · cited 131× · PMID 31921698 · DOI 10.3389/fonc.2019.01458
5. Role of immunotherapy in Ewing sarcoma.
   Morales E, Olson M, Iglesias F, Dahiya S, et al · · 2020 · cited 70× · PMID 33293354 · DOI 10.1136/jitc-2020-000653
6. Origin and Therapies of Osteosarcoma.
   Moukengue B, Lallier M, Marchandet L, Baud'huin M, et al · · 2022 · cited 60× · PMID 35884563 · DOI 10.3390/cancers14143503
7. Therapeutic Approaches Targeting PAX3-FOXO1 and Its Regulatory and Transcriptional Pathways in Rhabdomyosarcoma.
   Nguyen TH, Barr FG. · · 2018 · cited 54× · PMID 30373318 · DOI 10.3390/molecules23112798
8. Extraskeletal Myxoid Chondrosarcoma: State of the Art and Current Research on Biology and Clinical Management.
   Stacchiotti S, Baldi GG, Morosi C, Gronchi A, et al · · 2020 · cited 49× · PMID 32967265 · DOI 10.3390/cancers12092703