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

Advanced Solid Tumor Clinical Trial

Official title: Phase Ib/II Multicohort Trial of Different Schemes of PM14 in Monotherapy and in Combination With Radiotherapy in Soft Tissue Sarcomas and Other Solid Tumors

Status Recruiting

Clinical Trial 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.

Clinical Trial Description

Cohort A and B (Phase I, PM14 monotherapy, advanced STS): 20-25 patients approximately per cohort.

Cohort E (Phase II, PM14 monotherapy, advanced L-sarcomas): 28 patients; (Simon's two-stage Minimax design), errors: α= 0.05; β=0.80, option related to efficacy = 35% (6-month PFSR) (Sample size 15+13), success in 6-month PFSR of ≤ 15% will be considered as unacceptable (H0), and would not warrant further investigation (null hypothesis). Success in 6-month PFSR of ≥ 35% will be considered as an acceptable result warranting further investigation of the investigational drug (H1, alternative hypothesis). A total of 15 eligible and treated patients will be included in the first stage of the study. If ≤ 2 successes are observed, the trial will be stopped in this cohort with the conclusion that the experimental treatment should not be further investigated. Else (≥ 3 successes), patients will continue to be accrued until 28 eligible patients enter the study. If 8 or more successes are observed in those 28 patients, it will be concluded that the results of this trial warrant further investigation.

Cohort F (Phase II, PM14 monotherapy, other advanced sarcomas): 29 patients; (Simon's two-stage Optimal design), errors: α= 0.05; β=0.80. option related to efficacy = 30% (6-month PFSR) (Sample size 10+19), success in 6-month PFSR of ≤ 10% will be considered as unacceptable (H0), and would not warrant further investigation (null hypothesis). Success in 6-month PFSR of ≥ 30% will be considered as an acceptable result warranting further investigation of the investigational drug (H1, alternative hypothesis). A total of 10 eligible and treated patients will be included in the first stage of the study. If ≤ 1 successes are observed, the trial will be stopped in this cohort with the conclusion that the experimental treatment should not be further investigated. Else (≥ 2 successes), patients will continue to be accrued until 29 eligible patients enter the study. If 6 or more successes are observed in those 29 patients, it will be concluded that the results of this trial warrant further investigation.

Cohort C (Best scheme of PM14 plus RTP in advanced sarcoma, head & neck, other solid tumors)

Phase I (advanced): pulmonary and/or abdominal cohort (2 dose levels), head and neck cohort (2dose levels). 25 patients approximately.

Phase II (advanced STS): errors: α=0.05; β=0.80, option related to efficacy = 50% (ORR in irradiated nodules) (Sample size 9+15), success in ORR of ≤ 25 % will be considered as unacceptable (H0), and would not warrant further investigation (null hypothesis). Success in ORR of ≥ 50% will be considered as an acceptable result warranting further investigation of the investigational drug (H1, alternative hypothesis). A total of 9 eligible and treated patients will be included in the first stage of the study. If ≤ 2 successes are observed, the trial will be stopped in this cohort with the conclusion that the investigational combination should not be further investigated. Else (≥ 3 successes), patients will continue to be accrued until 24 eligible patients enter the study. If 10 or more successes are observed in those 24 patients, it will be concluded that the results of this trial warrant further investigation.

Cohort D (Best scheme of PM14 plus RTP in localized intermediate sarcoma)

Phase I (localized sarcoma): 2 dose levels, 10 patients approximate ly. Phase II (localized "intermediate risk" STS): errors: α=0.05; β=0.80, option related to efficacy = 30% (ORR in irradiated nodules) (Sample size 10+19), success in ORR of ≤ 10% will be considered as unacceptable (H0), and would not warrant further investigation (null hypothesis). Success in ORR of ≥ 30% will be considered as an acceptable result warranting further investigation of the investigational drug (H1, alternative hypothesis). A total of 10 eligible and treated patients will be included in the first stage of the study. If ≤ 1 successes are observed, the trial will be stopped in this cohort with the conclusion that the investigational combination should not be further investigated. Else (≥ 2 successes), patients will continue to be accrued until 29 eligible patients enter the study. If 6 or more successes are observed in those 29 patients, it will be concluded that the results of this trial warrant further investigation. ;

Related Conditions & MeSH terms

• Advanced Soft-tissue Sarcoma
• Advanced Solid Tumor
• Sarcoma

• NCT number: NCT05146440
• Study type: Interventional
• Source: Grupo Espanol de Investigacion en Sarcomas
• Contact: Patricio Ledesma
• Phone: 971 439 900
• Email: ensayos@sofpromed.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 23, 2021
• Completion date: May 31, 2026