Grupo Español de Investigación en Sarcomas

A Phase I dose-finding stage for the LB-100 plus doxorubicin combination is planned for an initial set of 9-18 patients (21-day cycles). After that, in the Phase II part, patients will be randomized (ratio 1:1) to either the experimental arm (LB-100 plus doxorubicin combination) or the control arm (doxorubicin alone) to, comparatively, evaluate the efficacy of the LB-100 plus doxorubicin combination vs. doxorubicin alone

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.

Phase II, multicohort, single arm, open-label, multicenter, international clinical trial with three cohorts (cohort A: Soft tissue sarcoma, cohort B: Bone tumors (osteosarcoma, chondrosarcoma and cohort C: Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas)) with 7 sites in Spain.
Main objective: To evaluate the overall response rate (ORR) in the irradiated nodules according to RECIST v1.1 criteria.
Treatment
Medication
Trabectedin at 1.5 mg/m2 24-h IV CI along with radiation therapy (30 Gy, 3 Gy/day for 10 days for non-extremity location and 45 Gy, 1.8 Gy/day for 25 days for extremity location of target lesion(s)), starting within 1 hour after the first trabectedin infusion withdrawal (day 2)) will be given every 3 weeks up to progression or intolerance.
Premedication
4 mg oral dexamethasone 24h and 12h before trabectedin administration, 20 mg IV dexamethasone 30 minutes before treatment. Ondansetron or analogue will also be given prior to trabectedin.