Ignite Creation Date:
2025-12-25 @ 4:42 AM
Ignite Modification Date:
2026-03-11 @ 3:20 PM
Study NCT ID:
NCT02684318
Status:
UNKNOWN
Last Update Posted:
2017-06-22
First Post:
2016-02-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study to Evaluate PM01183 in Combination With Olaparib in Advanced Solid Tumors
Sponsor:
Poveda, Andrés, M.D.
Organization:
Study Overview
Official Title:
Phase Ib/II Study to Evaluate the Efficacy and Tolerability of PM01183 in Combination With Olaparib in Patients With Advanced Solid Tumors
Status:
UNKNOWN
Status Verified Date:
2017-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Phase Ib/II study to evaluate the efficacy and tolerability of PM01183 in combination with olaparib in patients with advanced solid tumors.
Detailed Description:
The study will be split into 2 parts: an open label Phase I dose escalation part followed by a non-randomized Phase II part, as an expansion study, in patients with selected tumors at the recommended doses and schedule determined in the phase I.
Phase I: A dose escalation study will be performed in patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
Phase II: An expansion dose study selecting patients with potential tumors with possibly sensitivity to PARP inhibitors according to histology, including triple negative breast cancer, high grade serous platinum-resistant ovarian and endometrial cancer patients, or patients with molecular features such as endometrial cancer with PTEN loss, breast or ovarian cancer with PTEN loss, known BRCA1/2 germline, somatic mutation or somatic methylation.
OBJECTIVES:
Primary objectives:
Phase Ib: To establish the safety \[dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase II doses (RP2D)\], of orally administered olaparib in combination with PM01183 in patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
Phase II: To assess the efficacy in terms of Tumor response rate according to RECIST v1.1 criteria of PM01183 in combination with olaparib in the selected populations.
Secondary objectives
Phase Ib:
To explore the pharmacokinetics of PM01183 and olaparib when administered in combination. To determine the effects of the study treatment on the level of PARP activity and
DNA damage in:
* Peripheral blood mononuclear cells (PBMC).
* Circulating tumor cells (CTC).
* Tumor biopsy samples. To evaluate the preliminary antitumor activity (overall response rate) by RECIST of the combination in the exposed population.
Phase II:
Progression free survival. Overall Survival. Toxicity profile of the combination in patients enrolled in the study. To explore the possible correlation between the expression of certain biomarkers and the efficacy of this therapeutic approach.
STATISTICAL PROCEDURES
\- Sample size. Justification
Phase I:
Between 18-48 patients are expected to participate in the Phase Ib part of the study. The number of patients may vary depending upon the tolerability of the combination and the number of dose levels required to identify the MTD.
Phase II:
A total accrual up to 73 subjects would be required, according to an MinMax two-stages Simon design. With an α-error 0.05 and a power 90%, RR with a poor scenario according previous one would be 24%, and in a favourable scenario RR would reach 40%.
Progression-free survival according to previous reported is 3.5 months and the objective for the study is 6.5 months (n=56). According to this objective, the maximum sample size is 73 patients, and first sample size is 61 patients (upper limit for first stage rejection: 18).
Two stages are established:
1. In the first step 61 evaluable patients will be included in the study. If 18 or fewer responses are observed, the study will be stopped due to an inadequate response rate.
Efficacy data for the patients included at this first step will be reviewed by an independent assessment committee (IAC).
2. If 19 or more responses are observed recruitment will continue until the group has 73 evaluable patients. If 23 or fewer responses are detected among these 73 patients, it will be concluded that the regimen is not sufficiently active to warrant further testing. If 24 or more responses are observed it will be concluded that the regimen is sufficiently active to warrant further testing in posterior Phase III.
Phase I: A dose escalation study will be performed in patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
Phase II: An expansion dose study selecting patients with potential tumors with possibly sensitivity to PARP inhibitors according to histology, including triple negative breast cancer, high grade serous platinum-resistant ovarian and endometrial cancer patients, or patients with molecular features such as endometrial cancer with PTEN loss, breast or ovarian cancer with PTEN loss, known BRCA1/2 germline, somatic mutation or somatic methylation.
OBJECTIVES:
Primary objectives:
Phase Ib: To establish the safety \[dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase II doses (RP2D)\], of orally administered olaparib in combination with PM01183 in patients with advanced or metastatic solid tumors without established standard therapeutic alternatives.
Phase II: To assess the efficacy in terms of Tumor response rate according to RECIST v1.1 criteria of PM01183 in combination with olaparib in the selected populations.
Secondary objectives
Phase Ib:
To explore the pharmacokinetics of PM01183 and olaparib when administered in combination. To determine the effects of the study treatment on the level of PARP activity and
DNA damage in:
* Peripheral blood mononuclear cells (PBMC).
* Circulating tumor cells (CTC).
* Tumor biopsy samples. To evaluate the preliminary antitumor activity (overall response rate) by RECIST of the combination in the exposed population.
Phase II:
Progression free survival. Overall Survival. Toxicity profile of the combination in patients enrolled in the study. To explore the possible correlation between the expression of certain biomarkers and the efficacy of this therapeutic approach.
STATISTICAL PROCEDURES
\- Sample size. Justification
Phase I:
Between 18-48 patients are expected to participate in the Phase Ib part of the study. The number of patients may vary depending upon the tolerability of the combination and the number of dose levels required to identify the MTD.
Phase II:
A total accrual up to 73 subjects would be required, according to an MinMax two-stages Simon design. With an α-error 0.05 and a power 90%, RR with a poor scenario according previous one would be 24%, and in a favourable scenario RR would reach 40%.
Progression-free survival according to previous reported is 3.5 months and the objective for the study is 6.5 months (n=56). According to this objective, the maximum sample size is 73 patients, and first sample size is 61 patients (upper limit for first stage rejection: 18).
Two stages are established:
1. In the first step 61 evaluable patients will be included in the study. If 18 or fewer responses are observed, the study will be stopped due to an inadequate response rate.
Efficacy data for the patients included at this first step will be reviewed by an independent assessment committee (IAC).
2. If 19 or more responses are observed recruitment will continue until the group has 73 evaluable patients. If 23 or fewer responses are detected among these 73 patients, it will be concluded that the regimen is not sufficiently active to warrant further testing. If 24 or more responses are observed it will be concluded that the regimen is sufficiently active to warrant further testing in posterior Phase III.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: