Clinical Trial of PM60184 in Advanced Colorectal Cancer After Standard Treatment

• Sponsor: PharmaMar (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03427268
• Collaborator: (none)
• Enrollment: 32
• Locations: 5
• Arm: 1
• Actual Duration (Months): 12.8
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial will evaluate the efficacy of PM060184 in terms of progression-free survival at 12 weeks (PFS3) in advanced or metastatic Colorectal Cancer (CRC) patients with any KRAS mutation status (wild- type; mutated; or unknown status) progressing after standard treatments (fluoropyrimidine, irinotecan, and oxaliplatin).

Patients in this trial will receive PM060184 at a dose of 9.3 mg/m2 as a 30-minute intravenous (i.v.) infusion on Days 1 and 8 q3wk.

Condition or Disease	Intervention/Treatment	Phase
Advanced Colorectal Cancer	Drug: PM060184	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open-label, Multicentre Study of PM060184 in Patients With Advanced Colorectal Cancer After Standard Treatment.
• Actual Study Start Date: Jan 16, 2018
• Actual Primary Completion Date: Feb 11, 2019
• Actual Study Completion Date: Feb 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PM060184 PM060184	Drug: PM060184; PM060184: 9.3 mg/m2 PM060184 i.v. as a 30-minute infusion via a central or peripheral venous catheter.Dose can be rounded to the first decimal point. PM060184 will be administered on Day 1 and Day 8 q3wk. (Three weeks=one treatment cycle).

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival Rate at Three Months [Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 3 months]

   Progression-free survival rate at 12 weeks (PFS3), defined as the rate estimate of the percentage of patients who are alive and progression-free at 12 weeks (~3 months) after the first treatment administration. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures

1. Overall Survival (OS) [From the first day of treatment to the date of death or last contact, up to 12 months]

   Overall Survival (OS), defined as the time from the first day of treatment to the date of death or last contact.

2. Progression Free Survival (PFS) [Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 12 months]

   Progression-free survival (PFS), defined as the time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

3. Overall Response Rate (ORR) [Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 12 months]

   Overall Response Rate defined as the percentage of patients with either complete response (CR) or partial response (PR) according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; RECIST, Response Evaluation Criteria in Solid Tumors

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

1. Voluntarily written informed consent, obtained before the beginning of any study-specific procedures.

2. Age ≥ 18 years.

3. Histologically-cytologically documented adenocarcinoma of colon or rectum that has progressed to the last prior treatment before inclusion.

4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. If the only tumor lesion is situated in a previously irradiated area or in an area subjected to other loco-regional therapy, regression in the lesion must be demonstrated radiologically.

5. Previous treatment in any setting with fluoropyrimidine, oxaliplatin and irinotecan in any combination (unless any is contraindicated).

6. Adjuvant chemotherapy-based treatments count as prior therapy, as long as relapse had occurred during or within six months of completion of such therapies.

7. Cumulative dose of prior oxaliplatin (if any) must be known.

8. Prior cetuximab, panitumumab, bevacizumab, aflibercept, and regorafenib are allowed.

9. No more than two prior therapies for metastatic disease.

10. Washout periods for prior therapies (defined in relation to planned start of study treatment [first dose administration]):

11. At least three weeks since the last administration of an antineoplastic treatment (chemotherapy, biological, targeted or investigational therapies).

12. At least three weeks since radiotherapy involving up to 35% of bone marrow (radiotherapy involving > 35% of bone marrow is not allowed) or two weeks since the end of palliative radiotherapy including single doses.

13. At least four weeks since any major surgical procedure, open biopsy, or significant traumatic injury.

14. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

15. Life expectancy ≥ 3 months.

16. Adequate bone marrow, liver, and kidney function:

17. Hemoglobin ≥ 9 g/dL.

18. Absolute neutrophil count ≥ 1.5 × 109/L.

19. Platelet count ≥ 100 × 109/L.

20. Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula).

21. Albumin ≥ 2.5 g/dL.

22. Total serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), except in case of Gilbert syndrome.

23. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN (≤ 5.0 × ULN in the case of liver metastases).

24. Recovery to grade ≤ 1 from any toxicity due to previous therapy (including peripheral sensory/motor neuropathy but excluding alopecia).

25. Left ventricular ejection fraction (LVEF) by echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan within normal range (according to institutional standards).

26. Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure during the trial and up to six months after treatment discontinuation, and fertile male patients must agree to refrain from fathering a child or donating sperm during the trial and up to four months after treatment discontinuation.

EXCLUSION CRITERIA:

1. Prior exposure to PM060184.

2. Known hypersensitivity to the study drug class or study drug excipient in the formulation.

3. Patients with locally advanced disease amenable to local and/or curative therapy (surgery or radiotherapy) at study entry.

4. Other serious and/or relevant diseases or clinical situations that, in the opinion of the Investigator, are incompatible with the protocol (including any of the following):

5. History of another neoplastic disease (except for basal cell carcinoma of the skin, superficial bladder tumors, or properly treated carcinoma in situ of the uterine cervix or melanoma in situ) unless in remission for at least five years and with no recurrence.

6. Symptomatic cerebral and/or leptomeningeal metastasis, spinal cord compression or carcinomatous meningitis.

7. Neuropathy of any etiology (other than that caused by previous antineoplastic therapy).

8. History of cardiac disease, such as myocardial infarction, in the year prior to registration in the clinical trial; symptomatic/uncontrolled angina pectoris; congestive heart failure or uncontrolled cardiac ischemia; any type of uncontrolled arrhythmia, congenital and/or prolonged QT interval or abnormal LVEF, or uncontrolled arterial hypertension (according to the standards of the World Health Organization [WHO]).

9. History of significant psychiatric disease.

10. Active infection requiring antibiotic, antifungal or antiviral treatment that, in the opinion of the Investigator, could compromise the patient's capacity to tolerate the therapy.

11. Known active liver (hepatitis B or C or cirrhosis) or renal disease.

12. Known human immunodeficiency virus (HIV) infection.

13. Any other concomitant pathology that could jeopardize the patient's safety or commitment to complete the clinical trial.

14. Inability or refusal to comply with the protocol or with the clinical trial procedures.

15. Pregnancy or lactation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US017	Los Angeles	California	United States	90089-9181
2	CA001	Toronto	Ontario	Canada	ON M5G 2M9
3	ES001	Barcelona		Spain	08035
4	ES009	Madrid		Spain	28041
5	ES002	Valencia		Spain	46010

Sponsors and Collaborators

• PharmaMar

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 27, 2017
• Statistical Analysis Plan - Feb 20, 2018

More Information

Publications

None provided.

• Responsible Party: PharmaMar
• ClinicalTrials.gov Identifier: NCT03427268
• Other Study ID Numbers: PM60184-B-002-17
• First Posted: Feb 9, 2018
• Last Update Posted: May 24, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Recruitment Details	The first informed consent was signed on 16 January 2018 and the first study treatment administration was on 8 February 2018. The cutoff date for the results was 11 February 2019 (date of last follow-up).

Arm/Group Title	PM060184
Arm/Group Description	PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
Period Title: Overall Study
STARTED	32
COMPLETED	0
NOT COMPLETED	32

Baseline Characteristics

Arm/Group Title	PM060184
Arm/Group Description	PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	23 71.9%
>=65 years	9 28.1%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	17 53.1%
Male	15 46.9%
Race/Ethnicity, Customized (Count of Participants)
White	32 100%
Region of Enrollment (Count of Participants)
Canada	1 3.1%
Spain	31 96.9%
Eastern Cooperative Oncology Group Performance Status (Count of Participants)
PS 0	15 46.9%
PS 1	17 53.1%
Stage at diagnosis (Count of Participants)
Stage I	1 3.1%
Stage IIIB	5 15.6%
Stage IIIC	2 6.3%
Stage IV	17 53.1%
Stage IVA	3 9.4%
Stage IVB	3 9.4%
UK	1 3.1%
Primary tumor side (Count of Participants)
Left	22 68.8%
Right	10 31.3%
Histology grade at diagnosis (Count of Participants)
G1: Well differentiated	8 25%
G2: Moderately differentiated	18 56.3%
G4: Undifferentiated	1 3.1%
GX: Grade cannot be assessed	5 15.6%
KRAS mutation status (Count of Participants)
Mutated	25 78.1%
Not done	6 18.8%
Unknown	1 3.1%
Sites involved (Count of Participants)
1 site	5 15.6%
2 sites	12 37.5%
3 sites	8 25%
4 sites	5 15.6%
6 sites	1 3.1%
7 sites	1 3.1%
Peripheral neuropathy (Count of Participants)
Yes	19 59.4%
No	13 40.6%
Prior surgery (Count of Participants)
Yes	28 87.5%
No	4 12.5%
Prior radiotherapy (Count of Participants)
Concurrent	1 3.1%
Palliative	4 12.5%
No	27 84.4%
Prior anticancer lines (Count of Participants)
1 line	1 3.1%
2 lines	26 81.3%
3 lines	5 15.6%
Best response to last prior therapy (Count of Participants)
CR	2 6.3%
PR	3 9.4%
SD	14 43.8%
PD	9 28.1%
UK	4 12.5%
Weight (Kg) [Median (Full Range) ]
Median (Full Range) [Kg]	67
Height (cm) [Median (Full Range) ]
Median (Full Range) [cm]	166
Body surface area (m^2) [Median (Full Range) ]
Median (Full Range) [m^2]	1.8
Time from diagnosis of advanced disease to study entry (months) [Median (Full Range) ]
Median (Full Range) [months]	17.3
Time from first diagnosis to first PM060184 infusion (months) [Median (Full Range) ]
Median (Full Range) [months]	22.9
Time from prior last progression before study entry (months) [Median (Full Range) ]
Median (Full Range) [months]	1.2
Time from stop date of prior chemotherapy to study entry (months) [Median (Full Range) ]
Median (Full Range) [months]	1.8

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Rate at Three Months
Description	Progression-free survival rate at 12 weeks (PFS3), defined as the rate estimate of the percentage of patients who are alive and progression-free at 12 weeks (~3 months) after the first treatment administration. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 3 months

Outcome Measure Data

Analysis Population Description

2 patients were never treated; 1 treated patient not receive 2 administrations over 2 cycles.

Arm/Group Title	PM060184
Arm/Group Description	PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
Measure Participants	29
Number (95% Confidence Interval) [percentage of participants]	20.7 64.7%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS), defined as the time from the first day of treatment to the date of death or last contact.
Time Frame	From the first day of treatment to the date of death or last contact, up to 12 months

Outcome Measure Data

Analysis Population Description

2 patients were never treated; 1 treated patient not receive 2 administrations over 2 cycles

Arm/Group Title	PM060184
Arm/Group Description	PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
Measure Participants	29
Median (95% Confidence Interval) [months]	9.8

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression-free survival (PFS), defined as the time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 12 months

Outcome Measure Data

Analysis Population Description

2 patients were never treated; 1 treated patient not receive 2 administrations over 2 cycles

Arm/Group Title	PM060184
Arm/Group Description	PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
Measure Participants	29
Median (95% Confidence Interval) [months]	2.6

4. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Overall Response Rate defined as the percentage of patients with either complete response (CR) or partial response (PR) according to RECIST v.1.1. CR, complete response: disappearance of all lesions; PD, disease progression: ≥10% increase in target lesion size and does not meet tumor density criteria of PR density; PR, partial response: ≥10% decrease in target lesion size or ≥15% decrease in tumor density; SD, stable disease: none of the CR, PR, or PD criteria met; RECIST, Response Evaluation Criteria in Solid Tumors
Time Frame	Time from the first day of study treatment to the day of assessment of progression, death or last tumor evaluation, up to 12 months

Outcome Measure Data

Analysis Population Description

2 patients were never treated; 1 treated patient not receive 2 administrations over 2 cycles

Arm/Group Title	PM060184
Arm/Group Description	PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
Measure Participants	29
SD <3 months	9 28.1%
SD ≥3 months	7 21.9%
PD	13 40.6%

Adverse Events

Time Frame	Patients were assessed between study start date and study completion date, approximately 1 year
Adverse Event Reporting Description	Patient excluded for analysis of safety: Two patients were never treated
Arm/Group Title	PM060184
Arm/Group Description	PM060184 was administered i.v. via a central line or a peripheral venous catheter (in 30-min administration) at a dose of 9.3 mg/m2 on Day 1 and Day 8 every three weeks (q3wk) (three weeks = one treatment cycle) (dose can be rounded to the first decimal point).
All Cause Mortality
	PM060184
	Affected / at Risk (%)	# Events
Total	16/30 (53.3%)
Serious Adverse Events
	PM060184
	Affected / at Risk (%)	# Events
Total	6/30 (20%)
Blood and lymphatic system disorders
Febrile neutropenia	1/30 (3.3%)	1
Gastrointestinal disorders
Abdominal pain	1/30 (3.3%)	1
Diarrhoea	1/30 (3.3%)	1
General disorders
Pyrexia	1/30 (3.3%)	1
Infections and infestations
Pneumonia pneumococcal	1/30 (3.3%)	1
Investigations
Alanine aminotransferase increased	3/30 (10%)	3
Aspartate aminotransferase increased	3/30 (10%)	3
Blood bilirubin increased	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	PM060184
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
Anaemia	7/30 (23.3%)	14
Neutropenia	3/30 (10%)	3
Gastrointestinal disorders
Abdominal distension	2/30 (6.7%)	2
Abdominal pain	20/30 (66.7%)	66
Abdominal pain upper	5/30 (16.7%)	15
Constipation	19/30 (63.3%)	61
Diarrhoea	11/30 (36.7%)	33
Nausea	9/30 (30%)	23
Vomiting	4/30 (13.3%)	7
General disorders
Asthenia	22/30 (73.3%)	74
Chest pain	2/30 (6.7%)	4
Pyrexia	5/30 (16.7%)	10
Infections and infestations
Device related infection	2/30 (6.7%)	3
Investigations
Alanine aminotransferase increased	2/30 (6.7%)	2
Aspartate aminotransferase increased	3/30 (10%)	3
Blood bilirubin increased	3/30 (10%)	5
Gamma-glutamyltransferase increased	2/30 (6.7%)	2
Platelet count decreased	2/30 (6.7%)	2
Weight decreased	3/30 (10%)	7
Metabolism and nutrition disorders
Decreased appetite	10/30 (33.3%)	26
Musculoskeletal and connective tissue disorders
Arthralgia	5/30 (16.7%)	13
Musculoskeletal chest pain	2/30 (6.7%)	6
Nervous system disorders
Dysaesthesia	3/30 (10%)	10
Dysgeusia	2/30 (6.7%)	4
Hypoaesthesia	3/30 (10%)	9
Neurotoxicity	2/30 (6.7%)	7
Paraesthesia	14/30 (46.7%)	52
Peripheral sensory neuropathy	3/30 (10%)	12
Psychiatric disorders
Anxiety	2/30 (6.7%)	7
Insomnia	2/30 (6.7%)	9
Skin and subcutaneous tissue disorders
Alopecia	14/30 (46.7%)	54
Pruritus	2/30 (6.7%)	11
Vascular disorders
Deep vein thrombosis	2/30 (6.7%)	7
Hypertension	2/30 (6.7%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.