A randomized, open label, multicenter phase II/III trial of sacituzumab govitecan compared to standard of care in metastatic, refractory colorectal cancer patients (TROPHIT1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Heidelberg AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

4 Jun 2024 → 10 Mar 2026

Decision date (initial)

2024-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The overall objective of the trial is to investigate the efficacy of the antibody-drug conjugate Sacituzumab Govitecan (SG), a TROP2 targeted approach, in individuals diagnosed with Metastatic Colorectal cancer (mCRC).
The first single-arm part (PART I) of the trial investigates efficacy assessed by progression free survival. In case of high clinical efficacy, the second randomized part (PART II) investigates superiority of SG compared to standard of care (Physicians Choice).

Secondary objectives 1

1. Secondary objectives of PART I and PART II are: · To assess the overall survival (OS) · To assess the Overall response rate (ORR) · To assess the Disease control rate (DCR) · To assess the Duration of Response (DOR)

Conditions and MedDRA coding

Metastatic Colorectal cancer (mCRC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of UICC Stage IV mCRC, not eligible for local therapy
2. Women or men aged ≥ 18 years, no upper age limit
3. ECOG performance status ≤2
4. Patients must have failed standard therapy or were intolerable towards standard therapy which must include fluoropyrimidine, oxaliplatin and irinotecan. (Targeted therapies (in combination with chemotherapy) including antiangiogenic monoclonal antibody/fusion protein/small molecule (e.g. bevacizumab, aflibercept, ramucirumab) and anti-EGFR antibody (e.g. Cetuximab, Panitumumab) are allowed as previous therapies.)
5. No Irinotecan treatment within the last 6 months. Patients that received Irinotecan treatment more than 6 months prior to inclusion, must have been responsive to Irinotecan induction therapy (i.e., patients previously exposed to induction chemotherapy containing irinotecan must have presented CR or PR or else SD at least 3 months or at initial response assessment).
6. At least one measurable lesion according to RECIST 1.1 that can be accurately assessed at screening by computed tomography or magnetic resonance imaging and is suitable for repeated assessment or available CT scan of thorax and abdomen not older than 30 days before start of treatment (day 1 of cycle 1).

Exclusion criteria 11

1. Patient with a known hypersensitivity to any of the excipients of sacituzumab govitecan
2. Participation in other clinical trials involving an investigational drug(s) (Phases 1-4) or observation period of competing trials, respectively within 4 weeks prior to study entry. Patients participating in observational studies are eligible.
3. Taking medications that may interfere with SN-38 metabolism.
4. Have had a prior anticancer biologic agent within 2 weeks prior to enrollment or have had prior chemotherapy, targeted therapy, or radiation therapy within 2 weeks prior to enrollment AND have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs at the time of study entry.
5. Have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs due to a previously administered agent.
6. Have an active second malignancy.
7. History of significant cardiovascular disease ( NYHA ≥ III)
8. Clinical signs of active severe infection with or without requiring antibiotics.
9. Inadequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment (growth factor support is not allowed within 14 days prior to baseline labs
10. Known microsatellite instable (MSI-H) / MMR-protein deficient (dMMR) colorectal cancer.
11. Pregnancy and lactation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival (PFS): as the time from C1D1 (in part 1) or randomization (in part 2) into the study to time of progression of the disease or death from any cause, whatever occurs first.

Secondary endpoints 4

1. Overall Survival (OS): as time from C1D1 (in part 1) or randomization (in part 2) until death or end of study (EOS).
2. Overall Response rate (ORR): Partial Response (PR) or Complete Response (CR)
3. Disease Control Rate (DCR): Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
4. Duration of Response (DOR): as time from achievement of PR/CR until recurrence or progression of the disease or death from any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Heidelberg AöR

Sponsor organisation

Universitaetsklinikum Heidelberg AöR

Address

Im Neuenheimer Feld 672, Neuenheim Neuenheim

City

Heidelberg

Postcode

69120

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

Coordinating Investigator

Public contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications