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

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.