Early intervention and recovery of sexual function in men and women after treatment of rectal cancer–a randomized placebo-controlled study with tadalafil

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska Institutet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Decision date (initial)

2024-09-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-504592-24-00

EudraCT number

2017-004916-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis, Safety

To evaluate the effect of prophylactic intake of 5 mg tadalafil on sexual/erectile function in women and men within a standardized rehabilitation program after treatment for rectal cancer.

Secondary objectives 10

1. To evaluate the effect of prophylaxis of 5 mg tadalafil on severe sexual dysfunction (women) and on severe erectile dysfuntion (men) after treatment of rectal cance
2. To evaluate the effect of prophylaxis of 5 mg tadalafil on sexual activity in women after treatment of rectal cancer.
3. To evaluate the effect of prophylaxis of 5 mg tadalafil on attempt to intercourse in women after treatment of rectal cancer
4. To evaluate the effect of prophylaxis of 5 mg tadalafil on sexual activity in men after treatment of rectal cancer.
5. To evaluate the effect of number of patients with use of PDE5-inhibitors at own cost between 6 and 24 months after surgery.
6. To evaluate the effect of prophylaxis of 5 mg tadalafil on genital fibrosis after treatment of rectal cancer.
7. To evaluate the effect of prophylaxis of 5 mg tadalafil on androgen levels after treatment of rectal cancer.
8. To evaluate the effect of prophylaxis of 5 mg tadalafil on bowel function after treatment of rectal cancer.
9. To evaluate the effect of prophylaxis of 5 mg tadalafil on urinary function after treatment of rectal cancer.
10. To evaluate the effect ofthe safety and tolerability of 5 mg tadalafil during treatment of rectal cancer.

Conditions and MedDRA coding

sexual/ erectile function in women and men after treatment for rectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Men and women with rectal cancer stage I-III after clinical and radiologic staging, intention to transabdominal resection of rectal cancer.
2. Patient reported sexual activity before diagnosis or symptoms of rectal cancer according to FSFI-6 and IIEF-5.
3. Age over 18 years
4. Fluent in oral and written Swedish language
5. Females must not be lactating or pregnant at baseline documented by pregnancy test.
6. Given written informed consent

Exclusion criteria 9

1. Evidence of systemic disease (metastases)
2. History or evidence of urogenital malignancy
3. History of pelvic radiation
4. Concomitant use of anti-androgens or androgens
5. Contraindications to the use of tadalafil (PDE5-inhibitor)
6. Impaired performance status (Eastern Cooperative Oncology Group (ECOG) performance score above 1.
7. Serious co-existing mental disorder or medical condition e.g. anaemia, liver or renal failure, cardiovascular disease or diabetes.
8. Ongoing drug or alcohol abuse dependence.
9. Has a condition or has received medical treatment that, in the judgement of the investigator, precluded successful participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Women: Change between baseline and 24 months in sexual function assessed with the total score of the Female Sexual Function Index (FSFI- 6).
2. Men: Change between baseline and 24 months in erectile function assessed with the total score of the short version of the International Index of Erectile Function (IIEF-5).

Secondary endpoints 11

1. Change from baseline to 24 months on the proportion of women with severe sexual dysfunction defined as a FSFI-6 score below 20 at baseline and the proportion of men with severe erectile dysfunction defined as IIEF-5 score of 5-7 at baseline.
2. Change from baseline to 24 months on the proportion of sexually active women defined as score 0 on question 2, 3 or 4 in the FSFI-6 questionnaire at baseline.
3. Change from baseline to 24 months on the proportion of women who attempt intercourse defined as score 0 on question 6 in the FSFI-6 questionnaire at baseline.
4. Change from baseline to 24 months on the proportion of sexually active men defined as score "X" (no sexual activity) on question 2, 3, 4 or 5 in the IIEF-5 questionnaire at baseline.
5. Proportion of patients with use of PDE5-inhibitors at least once per month between 6-24 months after surgery for rectal cancer (PDE5- inhibitors users).
6. Fibrosis:Women: Change from baseline to 24 months in size of pain-free introducible vaginal dilator (4 XML File Identifier: pCoXtm4xKBCBEk2OP0cw1CYwmjU= Page 12/23 categories).
7. Fibrosis: Men: Change from baseline to 24 months in penile length in flaccid state
8. Change from baseline to 24 months in total and free testosterone, LH, albumin and sex hormone binding globuline (SHBG).
9. Change from baseline to 24 months in Low Anterior Resection Syndrome Score (LARS) or the Colostomy Impact Score (CI) respectively.
10. Change from baseline to 24 months in urinary function (questionnaire) – descriptive statistics.
11. Adverse events from baseline to 6 months after surgery for rectal cancer.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska Institutet

Sponsor organisation

Karolinska Institutet

Address

Nobels Vag 6

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Karolinska Institutet

Contact name

Anna Martling

Public contact point

Organisation

Karolinska Institutet

Contact name

Anna Martling

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

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

Documents 5 files

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

Application history

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