Multicohort Trial of Different Schemes of PM14 in Monotherapy and in Combination with Radiotherapy in Soft Tissue Sarcomas and Other Solid Tumor

NCT05146440 | Recruiting Phase 1

• 1 other identifier: GEIS-83
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 4

Brief Summary

Phase Ib/II, multicohort, single arm, open-label, multicenter, international clinical trial, with 6 cohorts (advanced STS, advanced L-sarcomas, other advanced sarcomas, advanced solid tumors, and localized STS) with 4 sites in Spain for phase I. The aim of this study is to explore different infusions of PM14 (longer or repeated) in order to obtain a potentially better efficacy and similar toxicity profile in advanced soft tissue sarcoma patients as monotherapy and also in other solid tumors as concomitant treatment with radiation therapy. Treatment Cohort A A phase I dose-finding stage for PM14 is planned with an estimated number of 20-25 patients. PM14 will be tested at different dose levels in 24-h IV infusion on day 1 of 21-day cycles, up to progression or unacceptable toxicity. Premedication with dexamethasone is recommended on the day before treatment initiation. Cohort B A phase I dose-finding stage for PM14 is planned with an estimated number of 20-25 patients. PM14 will be tested at different dose levels in 3-h IV infusion during 3 consecutive days (days 1-3) of 21-day cycles, up to progression or unacceptable toxicity. Premedication with dexamethasone is recommended on the day before treatment initiation. Cohort E PM14 will be administered at the recommended phase II dose (RP2D) according to the most convenient scheme. Cycles will be administered by central venous port. Premedication with dexamethasone is recommended on the day before treatment initiation. Cycles will be repeated every 21 days up to progression or unacceptable toxicity. Cohort F PM14 will be administered at the RP2D according to the most convenient scheme. Cycles will be administered by central venous port. Premedication with dexamethasone is recommended on the day before treatment initiation. Cycles will be repeated every 21 days up to progression or unacceptable toxicity. Cohort C Phase I: PM14 will be administered at the RP2D according to the most convenient scheme in 21-day cycles, at at different dose levels in combination with radiotherapy, up to progression or unacceptable toxicity. Cycles will be administered by central venous port. Premedication with dexamethasone is recommended on the day before treatment initiation and during 2 additional days (in the 24-hour infusion) and during 3 additional days (in the 3-hour infusion). Radiation therapy will start within 1 hour of PM14 infuser disconnection and will be administered with 3 Gy per fraction for 10 days (30 Gy in total). Phase II: PM14 will be administered at RP2D concomitant with radiation therapy. Cohort D Phase I: PM14 will be administered at the RP2D according to the most convenient scheme, in up to 3 x 21-day cycles in neoadjuvant setting, at different dose levels in combination with radiotherapy. Cycles will be administered by central venous port. Premedication with dexamethasone is recommended on the day before treatment initiation. Radiation therapy will start within 1 hour of PM14 infuser disconnection and will be administered with 1.8 Gy per fraction for 25 days (45 Gy in total). Phase II: PM14 will be administered at RP2D concomitant with radiation therapy.

Conditions

Advanced Soft-tissue Sarcoma; Advanced L-sarcomas; Other Advanced Sarcomas; Advanced Solid Tumor; Localized Soft-tissue Sarcoma

Outcome Measures

Primary Outcomes (6)

• Cohorts A, B, C To determine the maximum tolerated dose (MTD) of PM14 to be used as recommended phase 2 dose (RP2D).

  The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol.

  1 year

• Cohorts E and F To evaluate the progression-free survival rate (PFSR) at 6 months.

  PFSR-6m (according to central radiology review): Efficacy measured by the PFSR at 6 months, which is defined as the percentage of patients whodid not experience radiological progression according to RECIST v1.1 or death due to any cause since the date of enrollment until month 6 after date of enrollment

  6 months

• Cohort C phase I To determine the maximum tolerated dose (MTD) of PM14 to be used as recommended phase 2 dose (RP2D).

  The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the pro

  1 year

• Cohort C phase II To evaluate the overall response rate (ORR) in irradiated nodules only.

  This objective is considered as a surrogate of palliative relief. Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1). Only nodules included in the radiation field will be considered.

  8 weeks

• Cohort D phase I To determine the maximum tolerated dose (MTD) of PM14 to be used as recommended phase 2 dose (RP2D).

  The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol.

  1 year

• Cohort D phase II To evaluate the overall response rate (ORR).

  Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response(CR)or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).

  63 days

Secondary Outcomes (14)

• Cohorts A, B, E, F, C, D To evaluate the safety profile

  21 days

• Cohorts A, B, E, F, C, D To evaluate the overall response rate (ORR).

  8 weeks

• Cohorts A, B, C, D To evaluate the median of progression-free survival (mPFS).

  8 weeks

• Cohorts A, B, E, F, C To evaluate quality of life.

  3 weeks

• Cohorts A, B, E, F, C, D To contribute to translational studies.

  4 years

Study Arms (1)

PM14 in monotherapy and in combination with radiotherapy in STS and other solid tumors

EXPERIMENTAL

Cohort A : Phase I. PM14 24-h IV 21-d cycles, up to PD or toxicity. Dexamethasone recommended. Cohort B: Phase I. PM14 3-h IV infusion 3 d 21-d cycles, up to PD or toxicity. Dexamethasone recommended. Cohort E: PM14 at RP2D. Dexamethasone recommended. 21-d cycles up to PD or toxicity. Cohort F: PM14 at the RP2D. Dexamethasone recommended. 21-d cycles up to PD or toxicity. Cohort C: Phase I: PM14 at the RP2D, 21-d cycles in combination with radiotherapy, up to PD or toxicity. Dexamethasone recommended. Radiation therapy 3Gy/f 10 d. Phase II: PM14 at RP2D with radiation therapy. Cohort D: Phase I: PM14 at the RP2D, 3 x 21-d cycles in neoadjuvant setting, in combination with radiotherapy. Dexamethasone recommended. Radiation therapy 1.8Gy/f 25 d. Phase II: PM14 at RP2D with radiation therapy.

Drug: PM14

Interventions

PM14 DRUG

Pharmaceutical form: PM14 drug product is provided as a sterile lyophilized powder for concentrate for solution for infusion with a strength of 5.0 mg of the active moiety. Route of administration: PM14 drug product was developed for administration by the i.v. route. Before use, the vials are reconstituted with 10 mL of sodium chloride 9 mg/mL (0.9%) solution for infusion to give a solution containing 0.5 mg/mL of PM14. Prior to administration, the reconstituted DP solution should be further diluted with sodium chloride 9 mg/mL (0.9%) solution for infusion. Each vial of PM14 5.0 mg is a single use vial.

PM14 in monotherapy and in combination with radiotherapy in STS and other solid tumors

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohorts A, B, E, and F
• The patient must voluntarily sign the informed consent before any study test is conducted that is not part of routine patient care.
• Age: 18-75 years.
• A centralized diagnosis of DD liposarcoma or mixoid/hypercellular liposarcoma or leiomyosarcoma must be confirmed for patients in cohort E.
• A centralized diagnosis of other sarcomas includes: undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumors, sarcoma NOS, fibrosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, epithelioid sarcoma, clear cell sarcoma, dedifferentiated or aggressive features in solitary fibrous tumor, extraskeletal myxoid chondrosarcoma, angiosarcoma, epithelioid hemangioendothelioma,
• Patients must have received a previous chemotherapy line in advanced disease unless contraindicated or not indicated.
• Radiological disease progression must be documented within 6 months prior to study entry.
• The patient must have been considered eligible for systemic chemotherapy. A maximum of two previous lines for advanced/metastatic disease are allowed.
• Measurable disease according to RECIST v1.1 criteria.
• Performance status ≤1 (ECOG).
• Adequate bone marrow function (hemoglobin \>10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3). Patients with creatinine clearance ≥ 30 mL/min (Cockcroft and Gault's formula), transaminases ≤ 3.0 times the ULN, total bilirubin ≤ ULN, are acceptable.
• Men or women of childbearing potential must be using an effective method of contraception before entry into the study and throughout the same and for 3 months (men) and 6 months (women) after ending study treatment. Women of childbearing potential must have a negative serum or urine pregnancy test before study entry.
• Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA.
• Patient must have a central venous catheter for PM14 treatment.
• Cohort C

You may not qualify if:

• Cohorts A, B, E, and F
• Performance status ≥ 2 (ECOG).
• Plasma bilirubin \> ULN.
• Creatinine \> 1.6 mg/dL.
• History of other cancer with less than 5 years free of disease with the exception of adequately treated basal cell carcinoma or in situ cervical cancer.
• Patients who do not provide consent for mandatory biological samples (including those required for the translational study) cannot participate in the study.
• Significant cardiovascular disease (for example, dyspnea \> 2 NYHA).
• Significant systemic diseases grade 3 or higher on the NCI-CTCAE v5.0 scale, that limit patient availability, or according to investigator judgment may significantly contribute to treatment toxicity.
• Uncontrolled bacterial, mycotic or viral infections.
• Women who are pregnant or breastfeeding.
• Psychological, family, social or geographic circumstances that limit the patients' ability to comply with the protocol or informed consent.
• Patients participating in another clinical trial or receiving any other investigational product.
• Cohort C
• Previous treatment with radiotherapy (except if previous radiotherapy treatment plus planned study radiotherapy treatment allow tissue constrains).
• Performance status ≥ 2 (ECOG).

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (4)

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

RECRUITING

Study Officials

• Javier Martín Broto

  Hospital Universitario Fundación Jiménez Díaz

  STUDY DIRECTOR

• Javier Martínez Trufero

  Hospital Miguel Servet

  PRINCIPAL INVESTIGATOR

• Ana Sebio

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

• Claudia Valverde

  Hospital Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patricio Ledesma

CONTACT

971 439 900; ensayos@sofpromed.com

Claudia Marcote

CONTACT

971 439 900; cmarcote@sofpromed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase Ib/II, multicohort, single arm, open-label, multicenter, international clinical trial

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: December 6, 2021
• Study Start: November 23, 2021
• Primary Completion: November 30, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: March 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)