A multiple ascending dose study to evaluate the safety, tolerability and effect on tumor response of the mTOR inhibitor (RAD001) in combination with the IGF-1R antagonist (R1507) in patients with advanced solid tumors

Phase 1

• Conditions: PIb: solid malignancy that is metastatic or unresectable PII: C 1: Advanced metastatic renal cell carcinoma C 2: Advanced low- to intermediate grade metastatic or unresectable locoregional pancreatic neuroendocrine tumors + carcinoid tumors; MedDRA version: 9.1Level: LLTClassification code 10050076Term: Metastatic renal carcinoma; MedDRA version: 9.1Level: LLTClassification code 10065147Term: Malignant solid tumor; MedDRA version: 9.1Level: LLTClassification code 10052399Term: Neuroendocrine tumour; MedDRA version: 9.1Level: LLTClassification code 10026664Term: Malignant pancreatic islet neoplasm

• Registration Number: EUCTR2008-005806-38-FR
• Lead Sponsor: F.Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-08-06
• Study Completion: 2013-06-06
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

1. [Phase Ib] Patients must have histologically confirmed recurrent or refractory advanced solid malignancy with no known standard of care according to the judgment of the investigator (including Hodgkin’s and non-Hodgkin’s lymphoma)

[Phase II] Patients must have histologically confirmed:
• Advanced metastatic renal cell carcinoma (RCC) with evidence of progressive disease despite prior VEGFr- TKI therapy.
• Advanced low- to intermediate grade metastatic or unresectable locoregional pancreatic neuroendocrine tumors (pNET) and carcinoid tumors who have failed standard therapy and have evidence of progressive disease. Patients with either carcinoid or islet cell tumors
will be included in this cohort.

2. Measurable disease according to RECIST in Phase II

3. Male and female patients, = 18 years age

5. Patients with treated, asymptomatic, stable CNS metastases are eligible for enrollment only if:
• Patient has received prior treatment to the site(s) of CNS metastatic disease at least 4 weeks prior to treatment
• Patient has no requirement for glucocorticoids (discontinued at least 3 weeks prior to treatment)
• Patient is not taking anticonvulsants (discontinued at least 3 weeks prior to treatment)
• Patient has no overt evidence of neurological deficit

6. ECOG performance status 0-2

7. Patients must have adequate organ and marrow function

8. Negative pregnancy test (serum ß-HCG) within 7 days of startingStudy treatment in women of childbearing potential (both premenopausal women and women < 2 years after the onset of menopause).

10. HbA1c = 7% at screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior treatment with agents that act via inhibition of the IGF-1R
pathway.

2. Prior treatment with agents that act via mTOR inhibition (e.g. sirolimus, temsirolimus, everolimus) for the phase II portion only.

3. Patients with untreated CNS metastases.

5. Previous or current anti cancer therapy: Patients who are currently receiving any anti cancer therapy (other than those administered on this study) or who have received:
• Radiotherapy = 4 weeks prior to enrollment
• Chemotherapy (including biologic therapy) = 4 weeks prior to enrollment
• Patients who have received therapy more than 4 weeks prior to enrollment who have not recovered adverse events to = grade 1, (excluding alopecia)

7. History of allogeneic bone marrow transplantation or organ transplantation.

11. Patients who are pregnant or breastfeeding.

12. Fertile men and women of childbearing potential not employing an effective method of birth control throughout the trial and for 3 months after last study drug administration in both sexes. Women of childbearing potential must have a negative pregnancy test (serum ß- HCG) within the 7 days prior to study drug administration.

13. Known hypersensitivity to R1507 or its excipients or to RAD001 or compounds of similar chemical or biologic composition to RAD001.

14. Any known severe and/or uncontrolled medical conditions

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified