Trials / Unknown

UnknownNCT03475953

A Phase I/II Study of Regorafenib Plus Avelumab in Solid Tumors

Status: Unknown
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 747 (estimated)

Sponsor: Institut Bergonié · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

Assessment of the efficacy and safety of Regorafenib and Avelumab in patients with advanced or metastatic solid tumors (ten cohorts), once the Recommanded Phase II Dose (RP2D) has been determined (phase I trial). Assessement of the efficacy and safety of a low-dose of regorafenib (80mg/day) with avelumab in patients with advanced or metastatic colorectal tumors.

Detailed description

This is a multicenter, prospective open-labeled phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of Regorafenib given in combination with Avelumab (no dose escalation for Avelumab) in patients with advanced digestive solid tumors followed by independent phase II trials to evaluate the association of Regorafenib at the RP2D with Avelumab in 17cohorts of advanced or metastatic tumors : * Cohort A: Colorectal cancer not MSI-H or MMR-deficient * Cohort B: GIST * Cohort C: Oesophageal or gastric carcinoma * Cohort D: Biliary tract cancer, hepatocellular carcinoma * Cohort E: Soft-tissue sarcoma (STS) * Cohort F: Radioiodine-refractory differentiated thyroid cancer (RR-DTC) * Cohort G: Neuroendocrine gastroenteropancreatic tumors (GEP-NETs) * Cohort H: Non-small cell lung cancer (NSCLC) * Cohort I: Solid tumors (including soft-tissue sarcoma) with immune signature (TLS+). In addition, to evaluate in a phase II trial, the association of a low-dose of regorafenib (80mg/day) with avelumab : * Cohort A': colorectal not MSI-H or MMR-deficient (low dose) * Cohort J: urothelial cancer * cohort K: HPV-associated cancer with molecular confirmation p16 positive status * cohort L: triple netagtive brest cancer * cohort M: TMH-high solid tumors with status TMB-high already known * cohort N: MSI-high solid tumors with status MSI-high already known * cohort O: non clear-cell renal carcinoma * cohort P: malignant pleural mesothelioma

Conditions

Interventions

Type	Name	Description
DRUG	Phase 1 : Regorafenib	A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.). Patients will be allocated 3 dose levels of Regorafenib following a 3 + 3 design.
DRUG	Phase 1 : Avelumab	A treatment cycle consists of 4 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.). Avelumab will be administered on cycle 1 Day 15 as a 1-hour intravenous (IV) infusion (10mg/kg), repeated every two weeks thereafter (ie. Day 1 and Day 15 of each subsequent cycle, as a 1-hour intravenous infusion).
DRUG	Phase 2 : Regorafenib	Phase 2 : Regorafenib - All patients will be treated at the RP2D of regorafenib defined in the preliminary phase 1 trial with the same schedule as in the phase I.
DRUG	Phase 2 : Avelumab	Phase 2 : Avelumab - All patients will be treated with avelumab with the same schedule as in the phase 1 trial.
DRUG	Phase 2: low-dose Regorafenib	Phase 2 : Regorafenib - All patients will be treated at a fixed low-dose of regorafenib of 80 mg/day

Timeline

Start date: 2018-05-04
Primary completion: 2024-12-31
Completion: 2025-12-31
First posted: 2018-03-23
Last updated: 2023-03-03

Locations

7 sites across 1 country: France

Source: ClinicalTrials.gov record NCT03475953. Inclusion in this directory is not an endorsement.